Index

Key: b = boxed material; f = figures; s = structural formulas; t = tables; boldface = boldfaced terms

A

A. See adenine
A. See absorbance
A bands, 170, 171f
A kinase anchoring proteins (AKAPs), 420, 421f
A site. See aminoacyl site
AAA+ ATPase, 922, 923
AAT. See aspartate aminotransferase
abasic site, 280, 281f, 935
ABC excinuclease, 936
ABC transporters. See ATP-binding cassette transporters
abiotic production, 32f
Abl gene, 452b–453b
absolute configuration, 72, 72f
absorbance (A), 75b
absorption, of dietary fats, 602–603, 602f
ACAT. See acyl-CoA-cholesterol acyl transferase
ACC. See acetyl-CoA carboxylase
acceptor control, 687
acceptor control ratio, 687
accessory pigments, 705, 705f, 706f
acetaldehyde, oxidation of, 490f
acetals, 234
acetate, 588b
acetic acid, oxidation of, 490f
acetic acid–acetate buffer system, 58–60, 60f
acetoacetate, 619, 619s
- in diabetes mellitus, 877
- formation and use of, 619–621, 619f, 620f
acetoacetate decarboxylase, 619f, 621
acetoacetyl-ACP, 748, 749f
acetone, 619, 619s
- in diabetes mellitus, 877
- formation and use of, 619–621, 619f, 620f
- oxidation of, 490f
acetylation, 216, 217f
- of histones, 1075–1077, 1076t
acetylcholine, in neuronal signaling, 443–444, 444f
acetylcholine receptors, 380, 444
acetyl-CoA. See acetyl-coenzyme A
acetyl-CoA acetyl transferase, 773, 773f
acetyl-CoA carboxylase (ACC), 744
- malonyl-CoA formation by, 744–745, 745f
- regulation of, 752–753, 752f
- in regulation of fatty acid oxidation, 613, 616, 616f
acetyl-coenzyme A (acetyl-CoA), 13f, 13s, 745s
- amino acid degradation to, 640f, 647–648, 647f, 648f
- in cholesterol synthesis, 772–775, 773f, 775f, 776f
- in citric acid cycle, 587f, 609–611
- fatty acid oxidation to. See fatty acid oxidation
- in fatty acid synthesis, 747, 748–750, 748f, 750f
  - shuttling of, 751–752, 752f
- free energy of hydrolysis of, 481t, 482, 482f
- in glyoxylate cycle, 735–736, 736f
- ketone bodies from, 619–621, 619f, 620f
- in liver, 849, 850, 851f
- malonyl-CoA formation from, 744–745, 745f
- oxidation of. See citric acid cycle
- pyruvate kinase regulation by, 544, 544f
- pyruvate oxidation to, 545f, 574
  - allosteric and covalent regulation of, 593–594, 593f
  - oxidative decarboxylation reaction, 575, 576f
  - PDH complex coenzymes, 576, 576f, 577f
  - PDH complex enzymes, 576–577, 577f
  - PDH complex substrate channeling, 577–578, 578f
acetylene, oxidation of, 490f
N-acetylglucosamine, 243, 243f, 244
N-acetylglutamate, 637, 638, 638f
N-acetylglutamate synthase, 637, 638, 638f, 639f
N-acetylmuramic acid, 244
N-acetylneuramine phosphotransferase, 1044f
N-acetylneuraminic acid (Neu5Ac), 236f, 237, 254, 256f, 351
achiral molecules, 16f
acid dissociation constants $(K_{a}),$ 57, 57f
acid-base catalysis
- chymotrypsin, 205, 205f
- enzymatic, 186–187, 187f
acidic activation domain, 1082, 1082f
acidic R groups, 74f, 76
acidosis, 56, 621, 877
- in diabetes mellitus, 63–64, 63f, 620–621, 877
- effects of, 64
- ketone bodies causing, 620–621, 877
- metabolic, 631–632
acids
- amino acids as, 76–79, 78f, 79f, 80f
- as buffers, 59–64, 60f, 61f, 62f
- ionization of
  - acid dissociation constants and, 57, 57f
  - equilibrium constants and, 54–55
  - pH scale and, 55–56, 55t, 56f
  - pure water, 54, 54f
  - titration curves and, 58–59, 58f, 59f
AcMNPV. See Autographa californica multicapsid nucleopolyhedrovirus
aconitase, 581
- in citric acid cycle, 579f, 581–582, 583f, 584b–585b
cis-aconitate, 581
- in citric acid cycle, 579f, 581–582, 583f, 584b–585b
aconitate hydratase, 581
- in citric acid cycle, 579f, 581–582, 583f, 584b–585b
ACP. See acyl carrier protein
acquired immune deficiency syndrome (AIDS)
- protease inhibitors for, 208–209, 208f, 209f
- retrovirus as cause of, 990–991, 991f
- reverse transcriptase inhibitors for, 991b
- $T_{H}$ cells in, 165
ACTH. See adrenocorticotropic hormone
actin, 6, 8f, 169, 170f
- CDK phosphorylation of, 450
- myosin thick filament interactions with, 170–172, 172f
actin filaments, 8f
actinomycin D, 971
action potential, 443, 857
action potentials, voltage-gated ion channels producing, 443–444, 444f
action spectrum, 705, 706f
activation energy $(Δ G^{‡})$ , 25–26, 181
- in enzymatic reactions, 180–181, 181f
  - binding energy and, 185, 185f
- of transmembrane passage, 386, 386f
- rate constant relationship to, 182
activation-induced deaminases (AIDs), 1014
activators, 1056, 1057, 1058f
- DNA-binding, in transcription factor assembly, 1077–1080, 1079f, 1080f
- modular structure of, 1081–1083, 1082f
active site, 179, 979f
- enzyme catalysis at, 180, 180f
- of ribosomes, 1017, 1018f
active transport, 385f, 386
- against concentration or electrochemical gradient, 391–392, 391f
- ion gradients providing energy for, 398–399, 400f
- proton-motive force driving, 683, 683f
active transporters, 386
- ABC transporters, 395–396, 396f, 396t, 397b–398b
- P-type ATPases, 392–394, 393f, 394f
- V-type and F-type ATPases, 394–395, 395f
activity, 90
- of enzymes, 89–90, 90f
  - regulation of, 498–501, 499f, 499t, 500f, 500t, 501f
Actos. See pioglitazone
acute intermittent porphyria, 819b
acute lymphoblastic leukemia (ALL), 810
acute myeloid leukemia, 452b–453b
acute pancreatitis, 628
acyclovir, 929, 929s
acyl carrier protein (ACP), 747, 747f
- acetyl and malonyl group transfer to, 747–748, 748f
acyl groups
- in lipid bilayer, ordered states of, 377–378, 377f
- transfer of, 475–476
acyl phosphate, 518
acylation, in chymotrypsin mechanism, 204–208, 204f, 205f, 206f–207f
acyl-carnitine/carnitine cotransporter, 605, 606, 606f
acyl-CoA acetyltransferase, 608
- in fatty acid oxidation, 607f, 608
- in ketone body formation, 619f, 620
acyl-CoA dehydrogenase, 607, 607f, 671
- electron transfer by, 671, 672f
- genetic defects in, 616–617
acyl-CoA synthetases, 760
- in triacylglycerol and glycerophospholipid synthesis, 760, 761f
acyl-CoA-cholesterol acyl transferase (ACAT), 776, 777f
N-acylsphinganine, 768, 772f
N-acylsphingosine, 770, 772f
ADA. See adenosine deaminase
adaptor hypothesis, 1006f
adaptor proteins, 420
- multivalent, 439–442, 439f, 441f
ADARs. See adenosine deaminases that act on RNA
Addison disease, 866
adenine (A), 264, 264s, 265t
- base pairing of, 269f
- biosynthesis of, 825, 826f, 827f
- deamination of, 280, 281f
- degradation of, 833–836, 834f, 835f
- methylation of, 283
- origin of, 998–999, 999f
adenine nucleotide translocase, 683, 683f
adenosine, 266s
- in enzyme cofactors, 294–295, 295f
adenosine $3', 5' -cyclic monophosphate$ (cyclic AMP, cAMP), 296
- in epinephrine and glucagon action, 566f
- FRET studies of, 416b–417b
- as regulatory molecule, 295f, 296
- as second messenger
  - for β-adrenergic receptors, 413–416, 414f, 415f, 418f, 421f
  - ${Ca}^{2 +}$ crosstalk with, 428
  - other regulatory molecules using, 416b–417b, 420, 420t, 421f
  - removal of, 415f, 417
  - in triacylglycerol mobilization, 603, 604f
adenosine deaminase (ADA), 833, 834f
deficiency of, 834, 835
adenosine deaminases that act on RNA (ADARs), 1014, 1014f
adenosine diphosphate (ADP)
- ATP synthesis from, 487–488
- in coordinated regulation of cellular respiration pathways, 688–689, 689f
- in glycolytic pathway, 513f, 521
- in metabolic regulation, 502–503, 503t
- oxidative phosphorylation regulation by, 686–687, 688–689, 689f
- PFK-1 and FBPase-1 regulation by, 541–542, 541f, 542f
- as signaling molecule, 296
adenosine monophosphates, 267s
adenosine phosphoribosyltransferase, 835
adenosine triphosphate (ATP)
- from β oxidation of fatty acids, 608–609, 610b, 611t
- in brain, 855–856, 855f
- in Calvin cycle
  - requirements of, 722–724
  - source of, 719, 726f
- in cellular metabolism, 26f, 27
- as chemical energy carrier, 294, 294f
- in cholesterol regulation, 782, 782f
- in coordinated regulation of cellular respiration pathways, 688–689, 689f
- energy from, 21, 21f
- in fatty acid synthesis, 750–751
- glucose oxidation yield of, 589t, 686–687, 686t
- in glycolytic pathway
  - coupling of, 513–514
  - net gain of, 521
  - payoff phase of, 512f, 513, 513f, 518–521, 520f, 525f
  - preparatory phase of, 511–513, 512f, 513f, 514–517, 515f, 517f, 519f
- histidine biosynthesis from, 814, 815f
- hydrolysis of
  - free energy of, 479–481, 479f, 480t
  - hypoxia-induced inhibition of, 687, 687f
- in metabolic regulation, 502–503, 503t
- metabolism, role in, 26f
- muscle use of, 852–855, 854f, 855f, 856b–857b
- in nitrogen fixation, 800
- from oxidative phosphorylation, 659–660, 660f, 674–675
  - active transport energized by proton-motive force in, 683, 683f
  - ATP stabilization in, 677–678, 678f
  - ATP synthase $f_{o}$ and $f_{1}$ domains in, 677, 678f
  - conformations of ATP synthase β unit in, 678–680, 679f
  - NADH shuttle systems for, 683–684, 684f, 686f
  - nonintegral stoichiometries of $O_{2}$ consumption and ATP synthesis in, 682–683
  - oxidation and phosphorylation coupling in, 675–677, 675f, 676f
  - proton flow producing rotary motion in, 681–683, 681f
  - proton gradient driving ATP release in, 678, 678f
  - rotational catalysis in, 680–682, 680f, 681f
- PDH complex regulation by, 593–594, 593f
- PFK-1 and FBPase-1 regulation by, 541–542, 541f, 542f
- phosphoryl group transfers and
  - in assembly of informational macromolecules, 485–487
  - energy provided by, 482–484, 483f
  - free-energy change for ATP hydrolysis, 479–481, 479f, 480t
  - large free energies of hydrolysis, 481–482, 481f, 481t, 482f
  - in muscle contraction, 483, 487
  - reactions involved in, 484–485, 484f, 486b
  - in transphosphorylations between nucleotides, 487–488, 487f
- pyrimidine biosynthesis regulation by, 829, 829f
- pyruvate kinase regulation by, 544, 544f
- in replication initiation, 923
- as signaling molecule, 296
- in skeletal muscle contractions, 170–171, 172f
- spliceosome and, 977
- in succinyl-CoA synthetase reaction, 579f, 584–586, 586f
- synthesis of, by photophosphorylation, 716, 716f
- urea cycle use of, 638
S-adenosylhomocysteine, 641–642, 643f
S-adenosylmethionine (adoMet), 641
- as alkylating agent, 282f, 283
- in amino acid degradation, 641–642, 641f, 643f
adenylate (AMP), 265t, 486
- biosynthesis of, 825–827, 826f, 827f
- degradation of, 833–836, 834f, 835f
- in metabolic regulation, 502–503, 503t
- PFK-1 and FBPase-1 regulation by, 541–542, 541f, 542f
adenylate kinase, 487, 503, 829
adenylyl cyclase, 413
- in GPCR signaling
  - β-adrenergic system, 413, 414f, 415f, 416, 418f
  - other regulatory molecules using, 420, 420t, 421f, 425
- in triacylglycerol mobilization, 603, 604f
adenylyl groups, ATP donation of, 484–485, 485f
adenylylation, 217f, 485
- in ATP reactions, 484–485, 485f, 486b
adenylyltransferase, 803, 804f
adenylyltyrosine, 77s
ADH. See antidiuretic hormone
adipocytes, 602, 851
- beige, 852
- brown, 689–690, 690f, 851f, 852, 853f
- triacylglycerol mobilization out of, 603, 604f, 605f
- triacylglycerols in, 344–345, 344f
- white, 851–852, 851f
adipogenesis, gut microbial influence on, 874–875, 875f
adipokines, 846, 867
- adipose tissue production of, 867–868, 867f, 868f
adiponectin, 846, 869
- feeding behavior regulation by, 847t
- insulin sensitivity actions of, 869, 870f
adipose tissue
- beige, 852
- brown, 610b, 689–690, 690f, 851f, 852, 853f
- cortisol effects on, 865–866
- endocrine functions of, 867–868, 867f, 868f
- epinephrine effects on, 864–865, 866t
- glucagon effects on, 862–863, 863f, 863t
- glucose uptake by, 389, 390b
- glyceroneogenesis in, 762–763, 762f, 763f
- insulin effects on, 859–860, 859t, 860f
- metabolic functions of, 848f, 851–852, 851f, 853f
- in starvation state, 863–864, 864t, 865f, 866f
- triacylglycerol recycling in, 761f, 762
- white, 851–852, 851f
adoMet. See S-adenosylmethionine
ADP. See adenosine diphosphate
ADP-glucose, 733
ADP-glucose pyrophosphorylase, 735f, 735
ADP-ribosylation, 216, 217f, 424–425, 424f
adrenal gland, 846f
adrenaline. See epinephrine
β-adrenergic receptor kinase (βARK, GRK2), 418, 419, 419f
adrenergic receptors, 412
β-adrenergic receptors, 413
- cAMP as second messenger of, 412–413, 414f, 415f, 418f, 421
- cross talk in signaling by, 438, 438f
- desensitization of, 418–419, 419f
- as drug targets, 412
- termination of response by, 416–418
adrenocorticotropic hormone (ACTH, corticotropin), 845–846
- cAMP signaling by, 420
Adriamycin. See doxorubicin
adult stem cells, 1091
advanced glycation end products (AGEs), 239b
aerobic environments, 3
- respiration in, 574. See also cellular respiration
afamelanotide, 819b
affinity, of signal transduction, 409, 410f
affinity chromatography, 86
- of proteins, 84, 85f
  - tags for, 313–314, 313t, 314f
AFM. See atomic force microscopy
A-form DNA, 272, 273, 273f
A-form RNA, 276, 276f
African sleeping sickness, 201b–202b, 256, 838
agarose, 247t
AGEs. See advanced glycation end products
aggrecans, 250, 252f
aging
- mitochondrial role in, 694
- telomere role in, 993
agonists, 412
- of β-adrenergic receptors, 412, 414f, 419
AIDS. See acquired immune deficiency syndrome
AIDs. See activation-induced deaminases
AIR carboxylase, 825, 826f
AKAPs. See A kinase anchoring proteins
Akt. See protein kinase b
ALA. See α-linolenic acid
alanine, 72f, 74, 74s, 644, 809
- biosynthesis of, 809–810
- catabolism of, 640f, 644–647, 644f, 646t
- gluconeogenesis from, 533f, 538, 538t
- metabolism of, 626–627, 627f
  - ammonia transport from muscle to liver, 632–633, 632f
- properties and conventions associated with, 73t
alanine aminotransferase (ALT), 632, 632f
- tissue-damage assays using, 637b
alanylglutamylglycyllysine, 81s
Ala-tRNA synthetase, 1024f
Alberts, Alfred, 786b–787b
albinism, 646t
albumin, 603, 604f
alcohol consumption
- niacin deficiency and, 495
- thiamine deficiency and, 551, 578
alcohol dehydrogenase, 127f, 530
- competitive inhibition of, 198
- in ethanol fermentation, 530, 530f
alcohol fermentation. See ethanol fermentation
aldehyde, 265s
aldol condensation, 473, 474f
aldolase, 516
- in Calvin cycle, 721, 723f, 724
- in glycolytic pathway, 513f, 516, 517f
- inhibition of, 203f
aldonic acids, 237
aldoses, 230–231, 230f
- asymmetric centers of, 232, 232f
aldosterone, as cholesterol derivative, 356, 356f
aldotriose, 230
algal cell walls, heteropolysaccharides in, 244
alkaline phosphatase, 303t
alkalosis, 56, 64
alkaptonuria, 646t, 650
AlkB protein, 938, 939f
alkylated nitrogenous bases, 938, 939f
alkylating agents, 282–283, 282f
ALL. See acute lymphoblastic leukemia
allantoin, 834, 834f
allergic response, IgE role in, 167
alligators, lactic acid fermentation by, 529b
allopurinol, 835
- for African sleeping sickness, 838
- for gout, 835–836, 835f
allose, 233s
allosteric effectors, 213
- in metabolic regulation, 499f, 500, 500t
allosteric enzymes, 213
- conformational changes of, 214–215, 214f, 215f
- kinetic properties of, 215, 216f
- structure of, 214, 214f
allosteric modulators, 213
- of allosteric enzymes, 214–215
allosteric protein, 157
allosteric regulation
- of acetyl-CoA carboxylase, 752–753, 752f
- of amino acid biosynthesis, 814–816, 816f
- of carbamoyl phosphate synthetase I, 637–638, 638f
- carbohydrate and lipid metabolism integration by, 570
- of global carbohydrate metabolism, 568–570, 569f, 570f
- of glutamine synthetase, 803, 803f
- of glycogen phosphorylase, 565–567, 565f, 566f
- of glycolysis, 526
- in metabolic regulation, 498, 499f, 500, 500t
- of PDH complex, 593–594, 593f
- of PFK-1 and FBPase-1
  - by ATP, ADP, AMP and citrate, 541–542, 541f, 542f
  - by fructose 2,6-bisphosphate, 542, 543f
- of protein kinases, 413, 414f
- of pyrimidine biosynthesis, 829, 829f
- of pyruvate kinase, 544, 544f
- of ribonucleotide reductase, 832, 832f
all-trans-retinol, 357
- as hormone precursor, 357, 358f
Alper, Tikvah, 134b
α helix, 111–114, 112f, 112t, 113b, 123t
- amino acid sequence and stability of, 113–114
- in membrane proteins, 374–375
α oxidation, 618, 618f
α/β barrel, 124, 125f
ALT. See alanine aminotransferase
alternative splicing, 981, 981b–982b, 982, 983f
Altman, Sidney, 997
altrose, 233s
Alzheimer disease
- genes involved in, 331–333, 332f
- protein misfolding in, 133, 133f, 134–135
Amanita phalloides, 972
α-amanitin, 972
Amaryl. See glimepiride
Ames test, 930, 931f
amino acid arm, 1019, 1019f
amino acid biosynthesis, 804–805, 804f, 806t
- allosteric regulation of, 814–816, 816f
- chorismate pathways, 811–812, 812f, 814f
- α-ketoglutarate pathways, 806, 807f
- oxaloacetate and pyruvate pathways, 809–811, 811f
- 3-phosphoglycerate pathways, 806
- regulation of, 816f
- ribose 5-phosphate pathway, 812–814, 815f
- special classes of reactions in, 804–805, 804f
- transcription attenuation of genes for, 1067–1068, 1067f, 1069f
amino acid catabolism, 625, 626f
- carbon skeleton pathways, 639–640
  - branched-chain amino acid degradation, 640f, 651–653, 654f
  - conversion to α-ketoglutarate, 640f, 650, 651f
  - conversion to glucose or ketone bodies, 640–641, 640f
  - conversion to succinyl-CoA, 640f, 650–651, 652f, 653b
  - defects in, 646, 646t, 648–653, 649f, 653b, 654f
  - degradation to acetyl-CoA, 640f, 647–648, 647f, 648f
  - degradation to oxaloacetate, 640f, 653–654, 654f
  - degradation to pyruvate, 640f, 644–647, 644f, 645f, 646t
  - enzyme cofactors involved in, 641–644, 641f, 642f, 643f
- metabolic fates of amino groups, 626–627, 627f
  - alanine transport of ammonia, 632–633, 632f
  - ammonia toxicity and, 633
  - enzymatic degradation of dietary proteins, 627–628, 628f
  - glutamate release of ammonia, 630–631, 632f
  - glutamine transport of ammonia, 631–632, 632f
  - transfer of α-amino groups to α-ketoglutarate, 628–630, 629f, 630f
- nitrogen excretion via urea cycle, 633
  - citric acid cycle links to, 636–637, 636f
  - defects in, 638–639
  - enzymatic steps of, 633–636, 634f–635f
  - pathway interconnections reducing energetic cost of, 638
  - reactions feeding amino groups into, 634f–635f
  - regulation of, 637–638, 638f
d-amino acid oxidase, 646
amino acid residues, 70
- modified, 1037–1038, 1038f
amino acid sequences
- of α helix, 113–114
- biochemical information from, 96, 98b
- coding nucleotide sequences correlating with, 886, 886f
- comparisons of, 317–318, 318f
- determination of, 91
  - classical-based methods, 92–93, 92f, 92t, 93f
  - mass spectrometry, 93–95, 94f, 95f
- directed mutagenesis of, 312–313, 312f
- of hemoglobin and myoglobin, 153, 154f
- historical information from, 96–100, 99f, 100f
- of integral membrane proteins, topology predictions based on, 374–375, 375f, 376f
- nucleotide sequence relationship to, 263
- protein function and, 91–92
- tertiary structure and, 130–131, 130f
amino acids, 14s, 70. See also specific amino acids
- abbreviations for, 71, 73t
- acid-base properties of, 76–79, 78f, 79f, 80f
- activation of, 1015, 1016f, 1016t
  - aminoacyl-tRNA synthetases in, 1020–1023, 1020t, 1021f, 1023f, 1025b–1027b
- bacteria use of d-, 820
- biosynthesis of, 805–816, 805f
- breakdown of, 590
- as buffers, 61, 61f, 79
- carbon atom designations in, 71–72
- classification of, 73–76, 74f, 75b, 75f, 77f
- codons coding for, 886, 886f, 1007, 1007f
  - determination of, 1007–1009, 1007f, 1008t, 1009f, 1010b–1011b, 1012t
- dietary protein degradation to, 627–628, 628f
- electric charge of, 79
- essential, 638, 638t, 805
- in general acid-base catalysis, 186–187, 187f
- in genetic code, 1025b–1027b
- glucogenic, 538, 538t, 640
- in glyoxylate cycle, 735, 736f
- ketogenic, 640
- in liver, 850, 850f
- molecules derived from
  - biological amines, 821–822, 823f, 824f
  - creatine and glutathione, 819–820, 821f
  - NO, 822, 824f
  - plant substances, 820–821, 822f
  - porphyrins, 817–821, 817f, 819b, 820f
- nonessential, 805
- in peptides, 81, 81f
- $p K_{a}$ and hydropathy index of, 73t
- posttranslational modifications of, 1036–1039, 1038f
- protein synthesis initiation by, 1023–1030, 1023f, 1028f, 1030f, 1031t
- in proteins, 9f, 13, 14f, 72, 80–83, 82t, 83t
- structural features of, 71–72, 71f, 72f, 73t
- titration curves of, 78–79, 78f, 79f, 80f
- uncommon, 76, 77f
d-amino acids, bacteria use of, 820
amino groups
- metabolic fates of, 626–627, 627f
  - alanine transport of ammonia, 632–633, 632f
  - ammonia toxicity and, 633
  - enzymatic degradation of dietary proteins, 627–628, 628f
  - glutamate release of ammonia, 630–631, 632f
  - glutamine transport of ammonia, 631–632, 632f
  - transfer of α-amino groups to α-ketoglutarate, 628–630, 629f, 630f
- in urea cycle. See urea cycle
aminoacyl (A) site, 1028, 1028f
aminoacyl adenylate (aminoacyl-AMP), 1020, 1021f
aminoacyl-AMP. See aminoacyl adenylate
aminoacyl-tRNA synthetases, 1006, 1020, 1020t, 1021f, 1023f
- genetic code expansion and, 1025b–1027b
- proofreading by, 1020–1022
- tRNA interactions with, 1022–1023, 1023f
aminoacyl-tRNAs, 1006
- codons binding to, 1008, 1008t
- in elongation, 1030–1031, 1031f
- genetic code expansion and, 1025b–1027b
- structure of, 1020, 1022f
- synthesis of, 1020–1023, 1020t, 1021f, 1023f
γ-aminobutyric acid (GABA), 821
- biosynthesis of, 821–822, 823f
- receptors for, 444
δ-aminolevulinate, 817, 817f, 818f
aminopterin, 836–837, 836f
amino-terminal (N-terminal) residue, 81
amino-terminal modifications, posttranslational, 1037
aminotransferases, 628
- in transfer of α-amino groups to α-ketoglutarate, 628–630, 629f, 630f
ammonia
- glutamate and glutamine assimilation of, 802–803
- glutamate release of amino group as, 630–631, 632f
- nitrate assimilation producing, 795, 795f
- nitrogen fixation to, 795
- oxidation of, by obligate anaerobes, 795, 795f, 798b–799b
- toxicity of, 633
- transport of
  - by alanine, 632–633, 632f
  - by glutamine, 631–632, 632f
- urea production from, enzymatic steps of, 633–636, 634f–635f
ammonotelic species, 626
amoxicillin, 211, 212f
AMP. See adenylate
AMP-activated protein kinase (AMPK), 503, 869
- adiponectin actions through, 869, 870f
- catabolism and anabolism coordination by, 869–871, 870f
- in hormonal signaling, 847f
- leptin stimulation of, 869
- in metabolic regulation, 503
- in regulation of fatty acid oxidation, 616, 616f
- structure of, 870f
- in hormonal signaling, 847f
amphibolic pathway, 590
- citric acid cycle as, 590, 591f, 591t
amphipathic helix, 388, 388f
amphipathic solutes, 46
- examples of, 46t
- water structure effects of, 48, 48f
amphitropic proteins, 372, 373f
- reversible associations of, 376
ampholytes, 77
amphoteric substances, 77
amphotericin B, 361f
AMPK. See AMP-activated protein kinase
amplification, 409
- DNA
  - with cloning vectors, 304–309, 306f, 307f, 308f
  - PCR, 283–286, 285f, 288b–289b, 314–315, 315f
- in epinephrine and glucagon action, 566, 566f
- in GPCR signaling, 416, 418f
- in hormonal signaling, 843, 845–846
- multivalent adaptor proteins involved in, 440, 441f
- protein production
  - altered genes and proteins, 312–313, 312f
  - bacteria systems used for, 310, 310f
  - expression vectors for, 309, 310f
  - insect and insect virus systems used for, 311–312, 311f
  - mammalian cell systems used for, 312
  - tags for purification of, 313–314, 313t, 314f
  - yeast systems used for, 310–311
- in RTK signaling, 433f, 434–435, 434f
- in signal transduction, 409, 410f
- in vision signaling, 429, 429f
α-amylases, 523
amylo $(1 \to 4)$ to $(1 \to 6)$ transglycosylase, 563f
amyloid, 133, 133f, 134–135
- in Alzheimer disease, gene mutations affecting, 333
amyloidoses, 133, 133f, 134
amylopectin, 242, 242f, 733. See also starch
amylose, 242, 242f
- glycosidic bond in, 244f
- structure of, 243–244, 244f
amytal, 666–667, 667t
anabolism, 26, 462, 463f
- AMPK coordination of, 869–871, 870f
anaerobic environments, 3
- bacteria and archaea in, anammox by, 795, 795f, 798b–799b
- fermentation in, 514
  - ethanol, 514, 525f, 530, 530f, 531–532
  - foods and industrial chemicals produced by, 530–532
  - lactic acid, 514, 525f, 526, 529b
  - thiamine pyrophosphate in, 530, 531f, 532t
analytes, 94
analytical reagents, antibodies as, 167–168, 168f
anammox, 795f, 796, 798b–799b
anammoxosome, 799b
anaplerotic reactions, 590
- citric acid cycle intermediates from, 591t, 590, 591f
androgens, 786
- synthesis of, 785–787, 788f
anemia. See also sickle cell anemia
- folate deficiency causing, 643
- ${vitamin B}_{12}$ deficiency causing, 615b, 643
aneuploidy, 946b
ANF. See atrial natriuretic factor
Anfinsen, Christian, 130
angina pectoris, 423b
angiogenesis, VEGFR role in, in cancer, 452b–453b
animal cells, structure of, 6, 7f
anion exchangers, 86
- chloride-bicarbonate exchanger, 389–392, 391f
Anitschkov, N. N., 786b
annealing, 279
- DNA, 278–280, 279f, 280f
annular lipids, 375f
anomeric carbon, 234
anomers, 234
anorexigenic neurons, 868, 869f
anorexigenic peptide hormones, leptin stimulation of, 868–869, 869f
antagonists, 412
- of β-adrenergic receptors, 412, 414f
antenna chlorophylls, 706f
antenna molecules, 705
- in photosystem I, 710, 710f
- in photosystem II, 709
anterior pituitary, 846f, 847f
antibacterials, lysozyme, 210–211, 244
antibiotics, 906b
- amino acid racemization inhibitors, 820
- enzyme mechanisms in development of, 210–211, 212f, 213f
- fermentation and, 532
- ion gradient disruptors, 399, 400f
- nucleotide biosynthesis targets of, 838
- polyketides, 360, 361f
- protein synthesis inhibition by, 1039–1040, 1039f
- protein targeting disruption by, 1042, 1043f
- resistance to, 211, 213f, 396, 887
- riboswitches as targets of, 1073
- sulfa, 548b
antibodies, 165
- antigen binding by
  - affinity and specificity of, 167, 168f
  - analytical procedures based on, 167–168, 168f
  - sites of, 165–167, 166f
- recombination and, 954
anticoagulation, medical approaches to, 222, 360
anticodon arm, 1019f, 1020
anticodons, 1010, 1019f
- codon pairing with, 1010–1012, 1012f, 1012t
- variations in, 1010b–1011b
antidiuretic hormone (ADH), water regulation by, 400
antifungals, polyketides, 360, 361f
antigen, antibody binding of
- affinity and specificity of, 167, 168f
- analytical procedures based on, 167–168, 168f
- sites for, 165–167, 166f
antigenic determinant, 165
antigens, 165
antimycin A, 667t
antioxidants, lipid cofactors, 359–360, 359f
antiparallel strands, 271, 271f, 275f
antiport, 391, 391f, 399
$α 1 -antiproteinase,$ 220
anti-silencing factor 1 (ASF1), 901
antithrombin, heparan sulfate and, 249–250, 249f
antithrombin III (ATIII), 222
antitumor drugs, tumor resistance to, 396
antiviral therapy, 929–930
AP endonucleases, 935
AP site, 281f, 935
Apaf-1. See apoptosis protease activating factor-1
APC gene, mutations in, 455
apoB mRNA editing catalytic peptide (APOBEC), 1014, 1014f, 1015, 1015f
APOBEC. See apoB mRNA editing catalytic peptide
apoE, 778–779
apoenzyme, 179
apolipoproteins, 603, 777
- in plasma lipoproteins, 777, 778f, 779f, 779t
apolipoproteins B-48 (apoB-48), 603
apolipoproteins C-II (aspC-II), 603
apoprotein, 179
apoptosis, 355, 455, 691
- mitochondrial triggering of, 691, 692f
- phosphatidylserine triggering of, 378
- regulation of, 455–456, 456f
apoptosis protease activating factor-1 (Apaf-1), 691, 692f
apoptosome, 691, 692f
App(NH)p, 680, 680s
aptamers, 1000b
aquaporins (AQPs), 374f, 400
- water passage by, 400–401, 400t
aqueous solutions
- buffering of, 59
  - in cells and tissues, 61–63, 61f, 62f, 63f
  - conjugate acid-base pairs, 59–63, 60f, 62f
  - Henderson-Hasselbalch equation for, 60
- ionization in
  - acid dissociation constants and, 57, 57f
  - equilibrium constants and, 54–55
  - pH scale and, 55–56, 55t, 56f
  - pure water, 54, 54f
  - titration curves and, 58–59, 58f, 59f
- weak interactions in, 43–53
  - colligative properties and, 51–53, 51f
  - electrostatic, 46, 46t, 47f, 50t
  - entropy, 47, 47f
  - hydrogen bonding, 44–45, 44f, 45f, 46f, 50, 50t
  - macromolecular structure and function and, 49–51, 50f, 50t, 51f
  - nonpolar compounds, 47–49, 48f, 49f, 50t
  - nonpolar gases, 47, 47t
  - polar solutes, 45, 45f, 46f, 50, 50t
  - van der Waals interactions, 49, 49t, 50t
Arabidopsis thaliana, cellulose synthesis in, 701, 737f
arabinose, 232, 233s
arachidic acid, structure and properties of, 342t
arachidonate, 754
- eicosanoids derived from, 755, 758–759, 758f
- synthesis of, 754, 754f
arachidonic acid
- eicosanoids derived from, 355, 355f
- structure and properties of, 342t
Archaea, 3, 4f, 5–6, 5f
archaea
- cells of, 5–6, 5f
- nitrogen fixation by, 797–802, 797f, 800f, 801f
- obligate anaerobes, anammox by, 795, 795f, 798b–799b
- signaling in, 447f
archaeal tetraether lipids, 346
architectural regulators, 1057, 1078, 1079, 1079f
arcuate nucleus, 868
- insulin actions on, 869
- leptin receptors in, 868, 868f
ARF6, 424
arginase, 634
- in urea cycle, 634f–635f, 636
arginine, 74s, 76, 650, 806
- biosynthesis of, 806, 807f
- catabolism of, 640f, 650, 651f
- in general acid-base catalysis, 187f
- NO synthesis from, 822, 824f
- properties and conventions associated with, 73t
- in urea cycle, 634f–635f, 635, 636
- for urea cycle defects, 639
argininemia, 646t
argininosuccinase, 634
- in urea cycle, 634f–635f, 635
argininosuccinate, 636
in urea cycle, 634f–635f, 635
argininosuccinate synthetase, 634
- in urea cycle, 634f–635f, 635, 636
argininosuccinic acidemia, 646t
βARK. See β-adrenergic receptor kinase
aromatic amino acids, 820–821
aromatic R groups, 74f, 75–76, 75f
β-arrestin (βarr), 418, 419, 419f
arrestin 1, 431
arrestin 2, 418–419, 419f
ARSs. See autonomously replicating sequences
Artemis, 949–950, 950f
artificial chromosomes
- bacterial, 307, 308f
- human, 890
- yeast, 307–309, 890
artificial mRNA templates, genetic code cracking using, 1007–1009, 1007f, 1008t, 1009f, 1010b–1011b, 1012t
artificial sweeteners, 231b
ascorbic acid. See vitamin C
ASF1. See anti-silencing factor 1
asparaginase, 653, 654f
- for acute lymphoblastic leukemia, 810
asparagine, 74s, 76, 653, 809
- catabolism of, 653–654, 654f
- properties and conventions associated with, 73t
aspartame, 82s, 231b, 650
aspartate, 74s, 76, 653, 809
- biosynthesis of, 809, 816f
- in $C_{4}$ pathway, 730
- in citric acid cycle, 590
- in general acid-base catalysis, 187f
- gluconeogenesis from, 533f
- metabolism of, 627, 627f
  - carbon skeleton degradation, 653–654, 654f
  - in urea cycle, 634f–635f, 635, 636–637
- properties and conventions associated with, 73t
- in purine biosynthesis, 825, 825f
- in pyrimidine biosynthesis, 827–829, 828f, 829f
aspartate aminotransferase (AAT), 637
- tissue-damage assays using, 637b
aspartate transcarbamoylase (ATCase), 214–215, 215f, 216f, 828, 828f, 829, 829f
aspartate-argininosuccinate shunt, 636, 636f
aspartyl protease, 208
aspirin, 222
- as anticoagulant, 222
- lipoxin synthesis stimulation by, 356
- prostaglandin synthesis inhibition by, 758f, 355–356, 355f, 758
assisted protein folding, 132–133, 132f
association constant $(K_{a}),$ 150, 150f
asthma, 356
ATCase. See aspartate transcarbamoylase
atherosclerosis, 784, 784f
- reverse cholesterol transport by HDL countering, 785
- statin drugs and, 785, 786b–787b
ATIII. See antithrombin III
ATM, 447, 450, 455
ATM gene, mutations in, 454
atomic mass unit, 13b
ATP. See adenosine triphosphate
ATP synthase, 395, 677
- ATP release from, 678, 678f
- β unit conformations of, 678–680, 679f
- of chloroplasts, 716, 717–718
- $F_{1}$ domain of, 677–678, 678f, 679f
- in Fe-S reaction center, 708f
- $F_{o}$ domain of, 677–678, 679f, 680–682, 681f
- as F-type ATPase, 394–395, 395f, 677
- hypoxia-induced inhibition of, 687, 687f
- inhibition of, 667t
- orientation of, 717f
- in pheophytin-quinone reaction center, 708, 708f
- rotational catalysis by, 680–682, 680f, 681f
  - proton flow driving, 681–683, 681f
- structure and mechanism of, 717–718
ATP synthasome, 683, 683f
ATP6 gene, 695
ATPases
- AAA+, 922–923
- F-type, 394–395, 395f, 677
- ${Na}^{+} K^{+}$
  - ATP energy for, 487
  - in electrical signaling, 442–443, 443f
  - structure and mechanism of, 392–394, 393f, 394f
- P-type, 392–394, 393f, 394f
- V-type, 394–395, 395f
ATP-binding cassette (ABC) transporters, 395–396
- ATP use by, 395–396, 396f, 396t
- defects in, 396, 397b–398b
ATP-gated $K^{+}$ channels, 860, 862, 862f
- in insulin secretion, 861–862, 862f
ATR, 447, 450, 455
atractyloside, 667t
atrial natriuretic factor (ANF), 422b
attenuator, 1068, 1069f
aurovertin, 667t
autocrine hormones, 844
Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV), recombinant protein expression using, 311
automated DNA sequencing, 287, 290, 290f
automated DNA synthesis, 283, 284f
autonomously replicating sequences (ARSs), 928
autophosphorylation, 434
- of RTKs, 433f, 434
autotrophs, 4f, 5, 461
- carbon, oxygen, and water cycling by, 461–462, 462f
- nitrogen cycling by, 462, 462f
auxin, 821, 821f, 822f
Avandia. See rosiglitazone
Avastin. See bevacizumab
Avery, Oswald T., 270
Azotobacter vinelandii, 800–801
AZT, 991b

B

B cells, 165, 166
B lymphocytes, 165, 166
bacmids, 311, 312
BACs. See bacterial artificial chromosomes
Bacteria, 3, 4f, 5–6, 5f
bacteria. See also Escherichia coli
- cells of, 5–6, 5f
- cellulose synthesis in, 736–738, 737f
- chloroplasts evolution from, 717–718, 718f
- chromosomes of
  - artificial, 307, 308f
  - elements of, 887, 888f, 888t
  - structure of, 908–909, 908f
- d-amino acids in, 820
- DNA organzation in, 909–910, 910f
- DNA repair in, 931t. See also DNA repair
- DNA replication in. See DNA replication
- elongation in, 1030–1035, 1031f, 1032f, 1034f
- evolution of, 717–718, 718f
- fatty acid synthesis in, 745, 753
- gene regulation in
  - coordination of r-protein and rRNA synthesis, 1070–1071, 1070f, 1071f
  - genetic recombination, 1073, 1074f, 1074t
  - induction of SOS response, 1068–1070, 1070f
  - positive regulation of lac operon, 1066–1067, 1066f
  - sRNA regulation of mRNAs, 1071–1073, 1071f, 1072f
  - transcription attenuation of genes for amino acid biosynthetic enzymes, 1067–1068, 1067f, 1069f
- genetic code variations in, 1010b–1011b
- glutamine synthetase in, 802, 803f
- glycogen synthesis in, 733
- homologous genetic recombination in, 941–943, 941f, 942f, 943f
- initiation in, 1023–1030, 1023f, 1028f, 1030f
- introns in, 975
- lectins of, 255, 256f
- lipopolysaccharides of, 253, 253f
- mitochondrial evolution from, 34, 35f, 692–693, 693f
- nitrogen fixation by, 797–802, 797f, 800f, 801f
- obligate anaerobes, anammox by, 795, 795f, 798b–799b
- operons in, 1058–1060, 1058f, 1059f
- phospholipid synthesis in, 766f, 767
- photosynthetic, reaction centers of, 707–708
- protein targeting in, 1045–1046, 1046f
- recombinant protein expression in, 310, 310f
- ribosomal RNA processing in, 983–984, 983f
- ribosomes of, 1015–1018, 1018f
- signaling in, 447f
- transcription and translation coupling in, 1036, 1036f
- transcription in
  - poly(A) tail and, 980
  - rifampicin and, 971f
  - RNA polymerase in, 961–963, 962f, 963f
- transposition in, 951–953, 953f
bacterial artificial chromosomes (BACs), 307
- as cloning vectors, 307, 308f
bacterial cell walls, heteropolysaccharides in, 244
bacterial genes, naming conventions for, 914–915
bacterial transposons, 952
bacteriophages
- DNA of, 885f
- in recombinant DNA technology, 303t
- RNA, 993
bacteriorhodopsin, 372–373, 373f, 375f
baculoviruses, 311
- recombinant protein expression in, 311–312, 311f
Baker, David, 138b
baker’s yeast, ethanol fermentation by, 530, 530f
ball-and-stick models, 15, 15f
Ballard, John, 762
Baltimore, David, 988, 989
Banting, Frederick G., 876b
BAR domains, 382
- membrane curvature and, 382, 383f
barbiturates, P-450 enzyme metabolism of, 757b
bariatric surgery, 878–879, 879t
Barr body, 907b
basal transcription factors, 1078
- DNA-binding activators and coactivators in assembly of, 1077–1080, 1079f, 1080f
base pairs, 268, 269f
- in codon and anticodon recognition, 1010–1012, 1012f, 1012t
- in DNA replication, 918f, 919f
- DNA stability and, 280
- DNA structure determination and, 270–271, 271f
- Hoogsteen, 274, 275f
- RNA, 276–277, 276f, 278f
- in transcription, 963
base-excision repair, 931t, 934–935, 935f
bases
- amino acids as, 76–79, 78f, 79f, 80f
- as buffers, 59–63, 60f, 62f
- ionization of
  - acid dissociation constants and, 57, 57f
  - equilibrium constants and, 54–55
  - pH scale and, 55–56, 55t, 56f
  - pure water, 54, 54f
  - titration curves and, 58–59, 58f, 59f
- nucleotide. See nitrogenous bases
basic helix-loop-helix, 1064, 1064f
basic R groups, 74f, 76
basophils, in allergic response, 167
Bassham, James A., 719
BAT. See brown adipose tissue
Bateson, William, 1092b
BCRP. See breast cancer resistance protein
Beadle, George, 886
beef fat, fatty acid composition, 345f
beer, ethanol fermentation producing, 532f, 531–532
beeswax, 346, 346f
beige adipocytes, 852
Benson, Andrew, 719
benzene, lipid extraction using, 361
benzoate, for urea cycle defects, 638, 639f
Berg, Paul, 301, 304
beriberi, 551, 578
Bernard, Claude, 556
Best, Charles, 876b
beta blockers, 412
β-α-β loop, 123, 123f, 124, 125f
β barrel, 123, 123f, 374
- in membrane proteins, 374–375, 375f
β cells. See pancreatic β cells
β conformation, 112t, 114, 114f
β oxidation, 601
- of fatty acyl-CoAs, 609f
- as first stage of fatty acid oxidation, 606, 607f
- of odd-number fatty acids, 612–613, 613f, 614b–615b
- overview of, 616f
- in peroxisomes, 617–618, 617f, 618f
- of saturated fatty acids
  - acetyl-CoA oxidation in citric acid cycle, 609–611, 611t
  - four basic steps of, 607–608, 607f, 608f
  - hibernation fueled by, 610b
  - repetition of steps to yield acetyl-CoA and ATP, 608–609, 610b
- of unsaturated fatty acids, 611–612, 612f
β sheet, 114, 114f, 124f
β sliding clamp, 920, 925, 926f
β barrel, 123f
β conformation, 111, 112t, 114, 114f, 117t, 123t, 124
β-granule, 557–558, 558f
β strand, 124f
β turns, 112t, 114, 115f
bevacizumab (Avastin), 453b
Bextra. See valdecoxib
B-form DNA, 272, 273, 273f
BFP. See blue fluorescent protein
bicarbonate
- for acidosis, 64
- anion exchange of, 389–392, 391f
- malonyl-CoA formation from, 744–745, 745f
bicarbonate buffer system, 62–63, 62f
bicoid gene, 1088, 1089f
biguanides, 879t
bilayer, 368, 368f. See also lipid bilayer
bile acids, 352, 602, 602f, 776
- synthesis of, 776–777, 777f
biliary cholesterol, 777
bilirubin, 817, 818, 820f
biliverdin, 817, 818, 820f
binding
- allosteric enzyme response to, 214–215, 214f, 215f
- heterotropic, 157
- homotropic, 157
- protein-ligand. See protein-ligand interactions
binding energy $(Δ G_{B}),$ 183
- of ATP and ADP with ATP synthase, 677–678, 678f
- in enzyme catalysis
  - contributions of, 185–186, 186f
  - weak interactions creating, 183–186, 183f, 184f, 185f
- in glycolysis, 514
binding site, 147
- antibody, 165–167, 166f
- myoglobin, 149, 149f
- of proteins, 147
binding-change model, 681
- for ATP synthase, 680–682, 680f, 681f
biochemical reactions
- basic principles of, 472, 472f
- energy changes in. See bioenergetics
- equations for, 478
- free-radical reactions, 475, 475f
- group transfer reactions, 475–476, 476f
  - phosphoryl group. See phosphoryl group transfers
- internal rearrangements, isomerizations, and eliminations, 474, 475f
- oxidation-reduction reactions, 476–478, 477f, 488
  - dehydrogenases involved in, 493–494, 493f
  - dehydrogenation, 477f, 489–490
  - electron carriers in, 492–494, 493f
  - flavin nucleotides in, 495–496, 495f
  - free-energy change of, 491t, 492
  - half-reactions describing, 489
  - ${NAD}^{+}$ functions outside of, 494–495
  - NADH and NADPH in, 493–495, 493f, 495f
  - niacin deficiency and, 494, 495f
  - oxidation of glucose to ${CO}_{2},$ 492
  - reduction potentials for, 490–492, 491f, 491t
  - work provided by electron flow in, 488–489
- reactions making or breaking carbon-carbon bonds, 473–474, 474f, 475f
- repeating patterns of, 472–478
biochemical standard free-energy change $(Δ G^{'} °),$ 180
- of ATP synthesis on surface of ATP synthase, 677–678, 678f
- standard equilibrium constant relationship to, 182, 182t, 468–470, 468t, 469t
biochemistry, foundations of, 2, 2f
- cellular, 2–10, 2f, 3f, 4f, 5f, 7f, 8f, 9f
- chemical, 10–19, 10f, 11f, 12f, 13b, 13f, 14f, 14t, 15f, 16f, 17b, 18f, 19f
- evolutionary, 30–36, 31f, 32f, 33f, 35f
- genetic, 27–30, 28f, 29f
- models of, 15f
- physical, 19–27, 20f, 21f, 22b–23b, 24f, 26f
bioenergetics, 22
- of ATP phosphoryl group transfers
  - in assembly of informational macromolecules, 485–487
  - energy provided by, 482–484, 483f
  - free-energy change for ATP hydrolysis, 479–481, 479f, 480t
  - in muscle contraction, 483, 487
  - phosphorylated compounds and thioesters with large free energies of hydrolysis, 481–482, 481f, 481t, 482f
  - reactions involved in, 484–485, 484f, 486b
  - in transphosphorylations between nucleotides, 487–488, 487f
- of gluconeogenesis and glycolysis, 534, 535t, 537, 537t
- thermodynamics and
  - additive nature of free-energy changes, 471
  - first and second laws, 466–467, 467t
  - free energy sources of cells, 467
  - reactant and product concentration effects on actual free-energy changes, 470–471
  - relationship between standard free-energy change and equilibrium constant, 182, 182t, 468–470, 468t, 469t
biofuels, ethanol fermentation producing, 531–532
bioinformatics, 96
biological amines, amino acid decarboxylation producing, 821–822, 823f, 824f
biological tethers, 593f
bioluminescence, 486b
biomass, ethanol from, 730b–731b
biomolecules, 1
- abiotic production of, 32f
- carbon structure and functional groups, 10–11, 11f, 12f, 13f
- configuration and conformation, 14–18, 18f
- evolution of, 30–31, 32f
- interactions among, 18
- macromolecules. See macromolecules
- models of, 15, 15f
- small cellular, 11–12
- stereoisomerism of, 72
- stereospecific interactions of, 15, 18, 19f
- structural hierarchy, 9f
- three-dimensional structure of, 14–18, 15f, 16f, 18f, 19f
biosignaling. See signaling
biosynthesis. See anabolism
biosynthetic precursors, 3–5, 4f
biotin, 534, 590
- in acetyl-CoA carboxylase reaction, 744–745, 745f
- in amino acid degradation, 641, 641f
- 1,3-bisphosphoglycerate
  - free energy of hydrolysis of, 481, 481t, 482f
  - in glycolytic pathway, 512f, 513, 513f, 525f
- 2,3-bisphosphoglycerate (BPG), hemoglobin-oxygen binding regulation by, 161–162, 162f
- in pyruvate carboxylase reaction, 534, 535f, 590–591, 592f
Bishop, Michael, 990
1,3-bisphosphoglycerate, 481, 482f, 518
2,3-bisphosphoglycerate (BPG), 161, 162
bisulfite, DNA damage caused by, 282
bitopic membrane proteins, 372
Blackburn, Elizabeth, 993
blacktongue, 494, 495f
blindness, vitamin A deficiency causing, 358f, 358
Blobel, Günter, 1041
Bloch, Konrad, 775
blood
- ammonia transport in, 631–632, 632f
- buffering of, 62–63, 62f
- composition of, 857–859, 858f
- metabolic functions of, 857–859, 858f
- oxygen transport in, 153
blood coagulation
- medical control of, 222
- vitamin K in, 360
- zymogen cascade in, 220–223, 220f, 221f
blood glucose, 857–859, 858f
- concentration of
  - drops in, 503
  - measurements of, 238b–239b, 877
- global regulation of, 568–570, 569f, 570f
- glucose 1-phosphate replenishment of, 559–560
- hormonal regulation of, 858–859
  - cortisol in, 865–866
  - diabetes mellitus and, 875–877
  - epinephrine in, 864–865, 866t
  - during fasting and starvation, 863–864, 864t, 865f, 866f
  - glucagon effects in, 862–863, 863f, 863t
  - insulin effects in, 859–860, 859t, 860f
  - pancreatic β cell insulin secretion in, 860–862, 861f, 862f
- liver replenishment of, 849, 849f
blood group type, gangliosides and, 253, 351, 351f
blood plasma, 858, 858f
blood-brain barrier, glucose transport across, 389t
blue fluorescent protein (BFP), 416b–417b
blunt ends, 304, 305f
BMI. See body mass index
Bmp4 gene, 1092b–1093b
body mass index (BMI), 867
body mass regulation
- adiponectin effects in, 869, 870f
- AMPK role in, 869–871, 870f
- diet effects on, 871–872, 871f
- endocrine functions of adipose tissue, 867–868, 867f, 868f
- ghrelin, ${PYY}_{3 - 36}$ , and cannabinoid effects in, 872–874, 874f
- gut microbial effects on, 874–875, 875f
- insulin effects in, 869
- leptin effects in, 869, 869f
- mTORC1 pathway in, 871, 871f
Bohr, Christian, 160
Bohr effect, 160
boiling point, of water, 44–45
Boltzmann constant (k), 182, 467t
bond dissociation energy, 44
bone spurs, 251b
bonobo, human genome comparisons with, 329–331, 330f
Botox. See botulinum toxin
bottom-up signaling, hormonal, 846–847, 847f
botulinum toxin (Botox), 383
bovine spongiform encephalopathy (BSE), 134b–135b
box C/D snoRNPs, 984, 984f
box H/ACA snoRNPs, 984, 984f
Boyer, Herbert, 301
Boyer, Paul, 680
BPG. See 2,3-bisphosphoglycerate
brain
- ammonia in, 633
- during fasting or starvation, 863–864, 864t, 865f, 866f
- glucose requirements of, 533, 557, 855–856, 855f
- ketone body use by, 619
- metabolic functions of, 848f, 855–857, 855f
branch migration, 942
branch synthesis, 564f
branched-chain α-keto acid dehydrogenase complex, 651, 652, 654f
branched-chain amino acids, degradation of, 640f, 651–653, 654f
branched-chain ketoaciduria. See maple syrup
brassinolide, 356, 356f
brazzein, 231b
BRCA1 genes, mutations in, 454
BRCA1/2, 948b
breakdown of amino acids, 590
breast cancer, 948b
- hormone-based drugs targeting, 445
- protein kinase inhibitors for, 452b–453b
breast cancer resistance protein (BCRP), 396
brewing, ethanol fermentation in, 530, 530f, 531–532, 532f
Briggs, G. E., 190
3-bromopyruvate, for cancer treatment, 527b–528b
Brown, Michael, 781–782, 786b
brown adipose tissue (BAT), 610b, 690, 690f, 851f, 852, 853f
Bruce, Ames, 930
BSE. See bovine spongiform encephalopathy
Buchanan, John M., 825
Buchner, Eduard, 178, 511
buffering region, 60
buffers, 59
- amino acids as, 61, 61f, 79
- in cells and tissues, 61–63, 61f, 62f, 63f
- composition of, 58, 59–60, 60f
- Henderson-Hasselbalch equation for, 60
bundle-sheath cells, 729–731, 729f
trans- $Δ^{2}$ -butenoyl-ACP, 748, 749f
butter, fatty acid composition, 345f
butyrate, 874
butyryl-ACP, 748, 749f
Byetta. See exenatide

C

C. See cytosine
C. See flux control coefficient
c ring, 680, 681f, 682f
C segments, 954, 954f
c subunits, 682f
$C_{3}$ plants, 720, 732t
- photosynthesis in, 729–732, 729f
$C_{4}$ pathway, 729
$C_{4}$ plants, 729, 732t
- photosynthesis in, 729–732, 729f
${Ca}^{2 +}$ . See calcium ion
${Ca}^{2 +}$ ATPase, 393, 393f
${Ca}^{2 +}$ channels, voltage-gated, action potentials produced by, 443–444, 444f
${Ca}^{2 +} / calmodulin-dependent protein kinases$ (CaM kinases), 426
cadherins, 384
CAF1. See chromatin assembly factor 1
Cairns, John, 915, 919
calcitonin gene, 983f
calcium ion $({Ca}^{2 +})$
- in muscle contraction, 171, 172f, 427
- oscillations, 428f
- as second messenger, 425, 425t, 427f
  - space and time localization of, 425–428, 427f, 427t
- SERCA pump movement of, 393, 393f, 394f
calmodulin (CaM), 426
- ${Ca}^{2 +}$ binding by, 426–427, 427f, 427t
Calvin, Melvin, 719
Calvin cycle, 719
- in $C_{4}$ plants, 729–732, 729f
- in CAM plants, 732
- ${CO}_{2}$ fixation into 3-phosphoglycerate, 720–721, 724f, 728f
- light activation in, 720f, 725–726, 727f
- NADPH and ATP requirements for, 722–724, 724f
- 3-phosphoglycerate conversion to glyceraldehyde 3-phosphate, 720f, 721–722
- ribulose 1,5-bisphosphate regeneration, 720f, 722, 724f, 728f
- rubisco in, 719–722, 724f, 728f
- transport system for, 720f, 724–725, 725f, 726f
CaM. See calmodulin
CaM kinases. See ${Ca}^{2 +} / calmodulin-dependent protein kinases$
CAM plants, 732, 732t
cAMP. See adenosine $3', 5' -cyclic monophosphate$
cAMP receptor protein (CRP), 966, 1066, 1066f, 1067
cAMP response element binding protein (CREB), 420, 1084
cAMP response element (CRE), 1084
cAMP-dependent protein kinase, 413
- FRET studies of, 416b–417b
- in GPCR signaling
  - β-adrenergic system, 413–416, 414f, 415f
  - other regulatory molecules using, 416b–417b
  - β-adrenergic system, 418f
  - other regulatory molecules using, 420, 420t, 421f
Campto. See irinotecan
camptothecin, 906b
cancer, 948b. See also tumors
- DNA repair and, 932b
- hormone-based drugs targeting, 445
- mutations in, 930, 931f, 932b
- nonhomologous end joining and, 948–950, 950f
- protein kinase inhibitors for, 452b–453b
- retroviruses causing, 990–991, 990f, 991b
Candida albicans, genetic code variations in, 1011b
cannabinoids, body mass regulation by, 872–874, 874f
canthaxanthin, 360f
cap-snatching, 975
carbamoyl glutamate, for urea cycle defects, 639, 639s
carbamoyl phosphate, 827–829
- in pyrimidine biosynthesis, 827–829, 828f, 829f
- in urea cycle, 634f–635f, 635
carbamoyl phosphate synthetase I, 634
- deficiency, 646t
- regulation of, 637–638, 638f
- in urea cycle, 634f–635f, 635
carbamoyl phosphate synthetase II, 828, 828f
carbanions, 473, 551f
- in making or breaking of carbon-carbon bonds, 473–474, 474f, 475f
carbocations, 473
- in making or breaking of carbon-carbon bonds, 473–474, 474f, 475f
carbohydrate binding domain (CBD), 257
carbohydrate metabolism
- adenine nucleotides in, 502–503, 503t
- enzyme regulation in, 498–501, 499f, 499t, 500f, 500t, 501f
- global regulation of, 568–570, 569f, 570f
- glycogenolysis and glycogenesis coordination in
  - allosteric and hormonal regulation of glycogen phosphorylase, 565–567, 565f, 566f
  - allosteric and hormonal signals in global carbohydrate metabolism, 568–570, 569f, 570f
  - GSK3 mediation of insulin, 567–568, 568f
  - phosphorylation and dephosphorylation of glycogen synthase, 565–567, 567f, 568f
  - PP1 role in, 568, 569f
- glycolysis and gluconeogenesis coordination in, 539
  - ATP in allosteric inhibition of pyruvate kinase, 544, 544f
  - conversion of pyruvate to phosphoenolpyruvate, 544–545, 544f
  - fructose 2,6-bisphosphate in allosteric regulation of PFK-1 and FBPase-1, 542, 543f
  - hexokinase isozyme responses to glucose 6-phosphate, 539–541, 539f, 540b
  - reciprocal regulation of phosphofructokinase-1 and fructose 1,6-bisphosphatase, 541–542, 541f, 542f
  - transcriptional regulation of number of enzyme molecules, 545–546, 545t, 546f
  - xylulose 5-phosphate as key regulator in, 543–544
- lipid metabolism integration with, 570
- in liver, 849–850, 849f
- reaction equilibria and, 501–502, 502t
- steady state maintenance in cells and organisms, 498
- xylulose 5-phosphate as key regulator of, 543–544
carbohydrate response element binding protein (ChREBP), 545, 546, 546f
carbohydrate synthesis
- $C_{4}$ pathway in, 729–732, 729f
- cellulose synthesis in, 736–738, 737f
- glucose synthesis, 733
- glycogen synthesis, 733
- glycolate pathway in, 720–721, 725f, 728f
- integrated processes in, 738–739, 739f
- pentose phosphate pathway in, 719
- starch synthesis, 733, 735f
- sucrose synthesis, 733, 733f
carbohydrates, 9f, 18, 229
- analysis of, 258–260, 259f
- classes of, 229
- in glycoconjugates. See glycoconjugates
- information carried by, 247
  - lectin reading of, 254–257, 255f, 256f
  - lectin-carbohydrate interactions, 256–257, 257f, 258f
- monosaccharides, 229
  - asymmetric centers of, 232, 232f
  - cyclic structures of, 232f, 233–235, 234f, 236f
  - hexose derivatives in living organisms, 236–237, 236f
  - as reducing agents, 237, 238b–239b
  - symbols and abbreviations for, 240t
  - two families of, 230–231, 230f
- oligosaccharides, 229
  - analysis of, 258–260, 259f
  - in feeder pathways for glycolysis, 522f, 523–525
  - in glycoproteins, 251, 252f
  - glycosidic bond in, 240, 240t
  - information carried by, 247, 254–257, 255f, 256f, 257f, 258f
  - nomenclature of, 240, 240t
- polysaccharides. See polysaccharides
- synthesis of, 533f
carbon, 10–11
- oxidation levels, 476f
carbon, in biomolecules, 10–11, 11f, 12f, 13f, 14f
carbon bonds, 10–11, 11f
carbon cycle, 461–462, 462f
carbon dioxide $({CO}_{2})$
- biotin as carrier for, 590–591, 592f
- as buffer. See bicarbonate buffer system
- climate change and, 730b–731b
- glucose oxidation to. See glucose oxidation
- hemoglobin transport of, 160–161, 161f
- isocitrate oxidation to, 579f, 582, 583f
- α-ketoglutarate oxidation to, 579f, 582–584, 583f
- oxidation of, 490f
- in oxidation reactions, 476f
carbon dioxide $({CO}_{2})$ assimilation, 719
- into biomass, 720, 720f
- in $C_{3}$ plants, 729–732
- in $C_{4}$ plants, 729–732, 729f
- in CAM plants, 732
- ${CO}_{2}$ fixation into 3-phosphoglycerate, 720–721, 724f, 728f
- light activation in, 720f, 725–726, 726f
- NADPH and ATP requirements for, 722–724, 724f
- 3-phosphoglycerate conversion to glyceraldehyde 3-phosphate, 720f, 721–722
- ribulose 1,5-bisphosphate regeneration, 720f, 722, 724f, 728f
- stages of, 719–722, 720f
- stoichiometry of, 724f
- transport system for, 720f, 724–725, 725f
carbon dioxide $({CO}_{2})$ fixation, 719
- into 3-phosphoglycerate, 720–721, 724f, 728f
carbon fixation, 719
carbon flux, anthropogenic, 730b
carbon monoxide (CO)
- hemoglobin binding of, 158b–159b
- oxidation of, 490f
- oxidative phosphorylation interference by, 667t
- regulatory or signaling functions of, 818
carbon-assimilation reactions, 701f, 727
carbon-carbon bonds, biochemical reactions making or breaking, 473–474, 474f, 475f
carbon-fixation reactions, 701f
carbonic acid, as buffer. See bicarbonate buffer system
carbonic anhydrase, 160
carbonyl groups, 473, 473f
- in citric acid cycle, 579f, 580
- in fatty acid oxidation, 608, 608f
- in fatty acid synthesis, 748, 749f
carbonylcyanide-p-trifluoromethoxyphenylhydrazone (FCCP), oxidative phosphorylation uncoupling by, 676, 676f
2-carboxyarabinitol bisphosphate, 721f
γ-carboxyglutamate, 76, 77s
γ-carboxyglutamate (Gla) residues, 222, 1038f
carboxyl group, in fatty acid oxidation, 609f
carboxylic acids, 877
carboxyl-terminal (C-terminal) residue, 81
carboxyl-terminal domain (CTD), 968, 971f
carboxyl-terminal modifications, posttranslational, 1037
carboxypeptidase, 123t
carboxypeptidases A and B, 628
carcinogens, 451
cardiac muscle
- creatine kinase in, 857b
- glucose uptake by, 389, 390b
- metabolic functions of, 848f, 855, 855f
- NO effects on, 423b
cardiolipin, 347, 348f, 765
- in endomembrane system, 370, 370f
- membrane curvature and, 382
- synthesis of, 766f, 767, 768f, 769f
cardiovascular disease
- dysregulation of cholesterol metabolism in, 784–785, 784f, 786b–787b
- PUFA role in, 343
- trans fatty acid role in, 345, 345f
caretaker genes. See stability genes
carnitine, 605
carnitine acyltransferase 1, 605, 606f
- regulation of, 613, 616f
carnitine acyltransferase 2, 605, 606f
carnitine palmitoyltransferase 1 (CPT1), 605, 606f
- regulation of, 616f
carnitine palmitoyltransferase 2 (CPT2), 605, 606f
carnitine shuttle, 603, 605–606, 605f, 606f, 613
carotene, 360
β-carotene, 705
- as hormone precursor, 357, 358f
- light absorption by, 704f, 705
- structure of, 704f
carotenoids, 357, 705
- light absorption by, 705
- structure of, 704f
Caruthers, Marvin, 283
CAS. See cellular apoptosis susceptibility protein
casein kinase II (CKII), 567
- glycogen synthase regulation by, 567, 567f, 568f
caspase 8, in apoptosis, 455, 456f
caspase 9, in apoptosis, 455, 456f, 691, 692f
caspases, 691
- in apoptosis, 455, 456f, 691, 692f
catabasis, 759
catabolism, 26, 462, 463, 463f
- AMPK coordination of, 869–871, 870f
- high-energy phosphate compound synthesis, 484
catabolite repression, 1066, 1066f
catalase, 283, 617
catalysis
- enzymatic, 25–27, 26f, 177, 179–188, 188f
  - acid-base, 186–187, 187f
  - at active site, 180, 180f
  - binding energy in, 183–186, 183f, 184f, 185f, 186f
  - covalent, 187
  - kinetics of. See enzyme kinetics
  - metal ion, 187–188
  - principles of, 182–183
  - reaction rate and equilibrium effects during, 180–182, 180f, 181f
  - regulation of, 498–501, 499f, 499t, 500f, 500t, 501f
  - specificity of, 182–183, 185, 186f
  - thermodynamics of, 182, 182t, 470–471
  - transition state role in, 183–186, 183f, 184f, 185f
- by RNA, 31–33, 33f
  - ribozymes, 277, 278f, 999–1001, 1000b, 1001f, 1017
catalytic triad, 205
catecholamines, amino acid decarboxylation producing, 821, 823f
catenanes, 896, 927, 927f, 928f
cation exchangers, 86
cation-exchange chromatography, 86
- of proteins, 85f, 86
Caudal protein, 1088
caveolae, 381, 381f
- signaling protein segregation by, 442
caveolin, 381, 381f, 1047, 1047f
CD spectroscopy. See circular dichroism spectroscopy
CDK. See cyclin-dependent protein kinase
cDNA library, 316, 316f, 320f
cDNAs. See complementary DNAs
CDP. See cytidine diphosphate
CDP-diacylglycerol, 765
- in phospholipid synthesis, 765–767, 766f, 768f
Cech, Thomas, 976
Celebrex. See celecoxib
celecoxib (Celebrex), 758
cell cycle
- chromosome changes during, 898, 899f
- four stages of, 446–447, 447f
cell cycle regulation
- apoptosis, 455–456, 456f
- loss of
  - oncogene role in, 451, 452b–453b, 454
  - tumor suppressor gene role in, 454f, 455
- by protein kinases, 446–447
  - oscillating CDK levels in, 447, 447f, 448f, 449f, 450f
  - protein phosphorylation in, 449–450, 450f
cell envelope, 5, 5f, 6
cell fractionation, 6, 8f
cell senescence, telomere role in, 993
cell surface
- glycoproteins on, 253
- lectins on, 254–256, 255f, 256f
- proteoglycans on, 247–253, 247f, 248f, 249f, 252f
- sphingolipids at, as sites of biological recognition, 351
cell surface receptors, for hormones, 842–843, 843f
cell wall, 7f
cell walls, bacterial and algal, heteropolysaccharides in, 244
cells, 2–3, 2f, 9, 9f
- amino acid sources of, 625
- ATP concentrations in, 481
- bacterial and archaeal, 5–6, 5f
- buffers in, 61–63, 61f, 62f, 63f
- characteristics of, 2–3, 2f
- differentiation of, 1091f
- dimensions of, 3, 3f
- dynamic steady state maintenance in, 497–498
- energy sources and biosynthetic precursors of, 3–5, 4f
- eukaryotic, 6, 7f, 8f
- evolution of, 33–35, 35f
- fat sources of, 602
- first, 33–34, 35f
- free energy sources of, 467
- in immune response, 164–165
- macromolecules of, 8–9, 9f, 12–14, 14t, 15t
- membranes enclosing. See membranes
- protein concentrations in, 1054, 1055f
- protein import into, 1046–1048, 1047f
- protein localization within, 318–320, 318f, 319f, 320f
- small molecules of, 11–12
- supramolecular structures of, 8–9, 9f
- surface of, 3f
- in vitro studies of, 9, 9f
cellular apoptosis susceptibility protein (CAS), 1045f, 1046
cellular function, 317
cellular immune system, 165
cellular proteomes, 319
cellular respiration, 574
- acetyl-CoA oxidation. See citric acid cycle
- acetyl-CoA production, 574
  - oxidative decarboxylation reaction, 575, 576f
  - PDH complex coenzymes, 576, 576f, 577f
  - PDH complex enzymes, 576–577, 577f
  - PDH complex substrate channeling, 577–578, 578f
- ATP yield in, 686–687, 686t
- coordinated regulation of ATP-producing pathways in, 688–689, 689f
- oxidative phosphorylation. See oxidative phosphorylation
- stages of, 574, 575f
cellulase, 523
cellulose, 229, 243
- folding of, 243–244, 243f, 244f
- glycosidic bond in, 244f
- structural role of, 243, 243f
- structure of, 736, 737f
- structures and roles of, 247t
- synthesis of, 736–738, 737f
cellulose synthase, 737
CENPA, 904b
central dogma of molecular biology, 884
centromere, 890, 890f
ceramides, 350, 350f
- as intracellular signal, 355
cerebrosides, 350, 770
- synthesis of, 770, 772f
ceruloplasmin, lectin role in destruction of, 254
cetuximab (Erbitux), 453b
CF. See cystic fibrosis
CFP. See cyan fluorescent protein
CFTR. See cystic fibrosis transmembrane conductance regulator protein
cGMP. See guanosine $3', 5' -cyclic monophosphate$
cGMP PDE. See cyclic GMP phosphodiesterase
cGMP-dependent protein kinase, 123b, 422b
Chagas disease, 256
Chalfie, Martin, 319–320
Changeux, Jean-Pierre, 158
chaperones, 132, 132f
chaperonins, 132f, 133, 1037, 1037f
Chargaff, Erwin, 270
charged solutes, electrostatic interactions of, 46, 46t, 47f, 50t
Chase, Martha, 270
CHD family, 1075
chemical elements, 10, 10f
chemical energy
- light energy from, 486b
- nucleotides as carriers of, 294, 294f
- protein interactions modulated by
  - myosin and actin, 169, 170f
  - sliding of filaments, 170–172, 172f
  - thin and thick filament organization, 169–172, 171f
chemical equations, biochemical equations compared with, 478
chemical evolution, 30–31, 32f
chemical reactions
- activation energy of, 25–26, 181, 181f, 182, 185, 185f
- biological. See biochemical reactions
- cellular regulation of, 27
- of early cells, 33–34, 35f
- energy changes during, 24–27, 26f, 180–181, 180f, 181f, 185, 185f
  - in biological systems. See bioenergetics
- energy coupling of, 22–23, 24f
- enzyme catalysis of, 25–27, 26f, 177
  - acid-base, 186–187, 187f
  - at active site, 180, 180f
  - binding energy in, 183–186, 183f, 184f, 185f, 186f
  - covalent, 187
  - kinetics of. See enzyme kinetics
  - metal ion, 187–188
  - principles of, 182–183
  - reaction rate and equilibrium effects during, 180–182, 180f, 181f
  - regulation of, 498–501, 499f, 499t, 500f, 500t, 501f
  - specificity of, 182–183, 185, 186f
  - thermodynamics of, 182, 182t, 470–471
  - transition state role in, 183–186, 183f, 184f, 185f
- ground state of, 180, 180f
- intermediates of, 181, 181f
- $K_{eq}$ and $Δ G °$ of, 23–25
- of nucleic acids
  - denaturation, 278–280, 279f, 280f
  - DNA amplification, 283–286, 285f, 288b–289b
  - DNA chemical synthesis, 283, 284f
  - DNA methylation, 283
  - DNA sequencing, 287–293, 287f, 290f, 292f, 293f
  - nonenzymatic transformations, 280–283, 281f, 282f
- prebiotic, 998–999, 999f
- rate of. See reaction rates
- rate-limiting step of, 181
- thermodynamics of. See thermodynamics
- transition state of, 25–26, 26f, 180f, 181, 181f
chemical synthesis
- carbohydrate analysis using, 259–260
- of DNA, 283, 284f
- of proteins and peptides, 95–96, 97f
chemiosmotic model, 675
chemiosmotic theory, 659
- for ATP synthase in chloroplasts and mitochondria, 702f
- of oxidative phosphorylation, 659–660, 660f
  - nonintegral stoichiometries of $O_{2}$ consumption and ATP synthesis in, 682–683
  - oxidation and phosphorylation coupling in, 675–677, 675f, 676f
chemotaxis, in bacteria, 447f
chemotherapeutic drugs
- glycolysis-based targets of, 527b–528b
- nucleotide biosynthesis targets of, 836–838, 836f
- protein kinases inhibitors, 452b–453b
- topoisomerase inhibitors as, 906b
- tumor resistance to, 396
chemotrophs, 4f, 5
chi, 942
chimpanzee, human genome comparisons with, 329–330, 330f
ChIP. See chromatin immunoprecipitation
chiral centers, 16–17, 16f, 17b, 71
- in amino acids, 71, 72, 72f
- in monosaccharides, 232, 232f
chiral molecules, 16f
chitin, 243
- structural role of, 243, 243f
- structures and roles of, 247t
chloramphenicol, 1040, 1040s
chloride ion $({Cl}^{-}),$ CFTR protein transport of, 397b–398b
chloride-bicarbonate exchanger
- electroneutral anion cotransport by, 389–392, 391f
- membrane anchoring of, 380, 380f
chloroform, lipid extraction using, 361, 362f
chlorophyll aα, 704f
- absorption spectrum of, 705, 705f
- in LHCII, 705, 706, 706f
- in P680, 709
- in P700, 711
- in P870, 708
- in photosystem I, 709
- in photosystem II, 709
- structure of, 704f
chlorophyll b, 704f
- absorption spectrum of, 705, 705f
- in LHCII, 705, 706f
- in P680, 709
- in P700, 709
- in photosystem I, 709
- in photosystem II, 709
- structure of, 704f
chlorophylls, 704
- exciton transfer of, 705–707, 706f, 707f
- light absorption by, 704–705, 704f
- structure of, 704–705, 704f
chloroplast DNA (cpDNA), 887
chloroplasts, 6, 7f, 701
- ATP synthase of, 716
- chemiosmotic mechanisms in, 702f
- electron flow and, 701–704
- in endomembrane system, 370
- evolution of, 34, 35f, 717–718, 718f
- fatty acid synthesis in, 750–751, 751f
- galactolipids and sulfolipids in, 349, 349f
- genome of, 301
- gluconeogenesis in, 735–736, 736f
- introns in, 975
- light absorption by, 703f, 704–705
- photochemical reaction systems in, 709, 709f
- photosynthesis, 701–704
- $P_{i} -triose$ phosphate antiport system in, 724–725, 725f, 726f
- starch production in, 722, 733
- structure of, 701–702, 702f
cholecalciferol, 357
- as hormone precursor, 357f
cholecystokinin, 628
cholera, ganglioside interactions in, 351
cholera toxin, 424, 424f, 494
cholesterol, 352
- biosynthesis of, 773f
- carbon atoms, origins of, 773f
- fused carbon rings of, 352, 352f
- hormones derived from, 354
- as membrane lipid, 352, 352f
  - lipid bilayer fluidity and, 378
  - rafts of, 380–382, 380f, 381f
- metabolic fates of, 775–777, 777f
- receptor-mediated endocytosis of, 781–782, 781f
- steroid hormones derived from, 356, 356f, 776, 777f, 785, 788f
- synthesis of
  - alternative fates of intermediates in, 787–788, 788f
  - four stages of, 772–775, 773f, 775f, 776f
  - isoprene units in, 773f, 774
  - regulation of, 782–784, 782f, 783f, 784f, 786b–787b
- trans fatty acid effects on, 345, 345f
- transport of
  - by HDL, 778f, 778t, 779f, 779t, 780–781, 780f, 785, 785f
  - by plasma lipoproteins, 777–780, 778f, 778t, 779f, 779t
  - by receptor-mediated endocytosis, 781–782, 781f
  - regulation of, 782–784, 782f, 783f, 785f, 786b–787b
cholesteryl esters, 776, 777f
- endocytosis of, 781–782, 781f
cholestyramine, 786b
chondroitin sulfate, 245, 246f, 248f, 250
- in proteoglycan aggregates, 250, 252f
chorismate, in amino acid biosynthesis, 811–812, 811f, 812f, 814f
ChREBP. See carbohydrate response element binding protein
chromatids, sister, 944–946, 945f, 947f
chromatin, 899
- contents of, 898–899, 899f
- nucleosomes as fundamental units of, 900–902, 901f, 904b–905b
- transcriptionally active compared with inactive, 1075–1077, 1076t
chromatin assembly factor 1 (CAF1), 901, 904b
chromatin immunoprecipitation (ChIP), 904b–905b
chromatin modification and remodeling proteins, 1078
chromatin remodeling, 1075, 1076t, 1077, 1078, 1079f
chromatography
- carbohydrate analysis using, 259
- of lipids, 361–362, 362f
- of proteins, 84, 84f, 85f, 86
  - tags for, 313–314, 313t, 314f
chromosomal scaffolds, 902, 902f
chromosome territory, 904, 908f
chromosomes, 301, 885
- aneuploid, 946b
- artificial
  - bacterial, 307, 308f
  - human, 890
  - yeast, 307–309, 890
- bacterial
  - artificial, 307, 308f
  - elements of, 887, 888f, 888t
  - structure of, 908–909, 908f
- complete replication of, 950–951, 952f
- complexity of, 889–890, 889f, 890t
- disease gene localization on, 331–333, 332f
- elements of, 885–890
- eukaryotic, 887–890, 888t
- genes of, 886, 886f. See also genes
- mitochondrial, 692, 692t, 693f
- movement of, 169
- organization of, 903f
- segregation of, 946b
- structure of, 898–910
  - in bacteria, 908–909, 908f
  - cell cycle changes in, 898, 899f
  - chromatin, 898–899, 899f, 901f, 904b–905b, 1075–1077, 1076t
  - highly condensed structures, 902–905, 902f
  - histones, 899–900, 899f, 900f, 900t, 901f, 904b–905b, 1075–1077, 1076t
  - nucleosomes, 899f, 900–902, 900f, 901f, 902f, 904b–905b
  - SMC proteins, 908, 908f, 909f
- supercoiling in, 891, 891f, 892f
  - linking numbers describing, 893–895, 894f
  - plectonemic and solenoidal, 898, 898f
  - replication and transcription and, 891, 892f
  - topoisomerases changing, 895–898, 895f, 896f, 897f, 897t, 906b
  - underwinding of, 892–895, 893f, 894f, 895f
- viral, 885f, 886–887, 887t
chronic myeloid leukemia, 453b
chylomicrons, 602f, 603, 777
- cholesterol transport as, 777–778, 778f, 778t, 779f, 779t
chymotrypsin, 107f, 628
- inhibition of, 200f
- mechanism of, 204–208, 204f, 205f, 206f–207f
- residues, 123t
- structure of, 204f
- zymogens of, 220, 220f
chymotrypsinogen, 220, 220f, 628
- composition of, 82, 82t, 83t
Cialis. See tadalafil
cimetidine (Tagamet), 822
cinnamate, 822f
Cipro. See ciprofloxacin
ciprofloxacin (Cipro), 906b
circular dichroism (CD) spectroscopy, 116, 116f
cis-trans isomers, 15, 15f
citrate, 581
- asymmetric reactions of, 588b
- citric acid cycle formation of, 579f, 581, 581f, 582f, 587f
- PFK-1 and FBPase-1 regulation by, 541f, 542, 542f
- PFK-1 regulation, 689
- in regulation of fatty acid synthesis, 752–753, 753f
- shuttling of acetate as, 751–752, 752f
citrate lyase, 751, 752f
citrate synthase, 477b, 581, 751, 752f
- in citric acid cycle, 579f, 581, 581f, 582f, 596f
- regulation of, 593f, 594
- structure of, 581, 581f
citrate transporter, 751, 752f
citric acid cycle, 574
- acetyl-CoA production for, 574
  - allosteric and covalent regulation of, 593–594, 593f
  - from fatty acid oxidation, 606, 607f, 609–611, 611t
  - oxidative decarboxylation of pyruvate, 575, 576f
  - PDH complex coenzymes, 576, 576f, 577f
  - PDH complex enzymes, 576–577, 577f
  - PDH complex substrate channeling, 577–578, 578f
- anaplerotic reactions replenishing intermediates of, 590, 591f, 591t
- biosynthetic intermediates from, 590, 591f, 591t
- biotin as ${CO}_{2}$ group carrier in, 590–591, 592f
- cancer-causing mutations in, 594–595, 595f
- catabolic and anabolic processes, 590
- chemical sense of reaction sequence used in, 579f, 580
- conservation of energy of oxidations in, 587–589, 589t
- as cyclic metabolic pathway, 579f
- eight steps of, 580–587
  - conversion of succinyl-CoA to succinate, 579f, 584–586, 586f
  - formation of citrate, 579f, 581, 581f, 582f, 587f
  - formation of isocitrate via cis-aconitate, 579f, 581–582, 583f, 584b–585b
  - hydration of fumarate to malate, 579f, 587
  - oxidation of α-ketoglutarate to succinyl-CoA and ${CO}_{2}$ , 579f, 582–584, 583f
  - oxidation of isocitrate to α-ketoglutarate and ${CO}_{2}$ , 579f, 582, 583f
  - oxidation of malate to oxaloacetate, 579f, 587
  - oxidation of succinate to fumarate, 579f, 586
- gluconeogenesis from intermediates of, 533f, 538, 538t
- in liver, 849, 850f
- products of, 587f
- reactions to, 578–580
- regulation of
  - allosteric and covalent regulation of PDH complex, 593–594, 593f
  - defects in, 594–595, 595f
  - at exergonic steps, 594
  - substrate channeling, 595, 595f, 596f
- as stage in cellular respiration, 574, 575f
- urea cycle links to, 636–637, 636f
citrulline, 76, 77s
- in urea cycle, 634f–635f, 635, 636
CKII. See casein kinase II
${Cl}^{−}$ . See chloride ion
Claisen condensation, 473–474, 474f, 608
- as first step of citric acid cycle, 579f, 581f, 582f
- as first step of fatty acid synthesis, 748, 749f
class I aldolase, 513f, 516, 517f
clathrates, 48
clathrin, 1046, 1047f
Claude, Albert, 6
Clausius, Rudolf, 22b
clavulanic acid, 211, 213f
Cleland, W. W., 195
Cleland nomenclature, 194f, 195
climate change, 730b–731b
clonal selection, 165
clone, 167, 302
cloning. See DNA cloning
cloning vectors, 302
- BACs, 307, 308f
- expression, 309, 310f
- plasmids, 305–306, 306f, 307f
- YACs, 307–309
clopidogrel (Plavix), 296
closed complex, 964
closed system, 20
closed-circular DNAs, 892, 894
Clostridium acetobutyricum, 532
Clostridium botulinum toxin, 383
Clostridium tetani toxin, 383
CMP. See cytidylate
CO. See carbon monoxide
${CO}_{2}$ . See carbon dioxide
CoA. See coenzyme A
coactivators, 1079–1080
- DNA-binding, in transcription factor assembly, 1077–1080, 1079f, 1080f
coagulation cascade, 220–223, 220f, 221f
- vitamin K in, 360
coated pits, 1046, 1047f
cobalamin. See ${vitamin B}_{12}$
cobrotoxin, 444
coding strand, 962
CODIS. See Combined DNA Index System
codon bias, 1011b
codons, 886, 886f, 1007, 1007f
- anticodon pairing with, 1010–1012, 1012f, 1012t
- determination of, 1007–1009, 1007f, 1008t, 1009f, 1010b–1011b, 1012t
- genetic code expansion and, 1025b–1027b
- initiation, 1009
  - protein synthesis initiation by, 1023–1030, 1023f, 1028f, 1030f, 1031t
- termination, 1009
- variations in, 1010b–1011b
coelacanths, lactic acid fermentation by, 529b
coenzyme A (CoA), 294–295, 295f, 576s, 606
- in PDH complex, 576, 576f, 577f
coenzyme $B_{12},$ 613, 613f, 614b–615b
coenzyme Q. See ubiquinone
coenzymes, 2, 178. See also specific coenzymes
- adenosine in, 294–295, 295f
- as electron carriers, 492–494
- examples of, 178t, 179t
cofactors, 178, 478. See also specific cofactors
- adenosine in, 294–295, 295f
- in amino acid degradation, 628–630, 629f, 630f, 641–644, 641f, 642f, 643f
- inorganic ions serving as, 178, 178t
- for intron splicing, 975, 976f
- lipids as
  - dolichols, 359f, 360
  - lipid quinones, 359–360
  - vitamins E and K, 359–360
Cohen, Stanley N., 301
cohesins, 908, 908f, 909f, 944
cointegrate, 953
collagen, 118
- structure and function of, 118–120, 119b, 119f, 120f
collagen fibrils, 120, 120f
colligative properties, 51
- of aqueous solutions, 51–53, 51f
Collins, Kathleen, 141, 142
Collip, J. B., 876b
color blindness, 430b
color vision, 430b, 430f
colorectal cancer, mutations in, 454f, 455
column chromatography, 84
- of lipids, 362, 362f
- of proteins, 84, 84f, 85f, 86
combinatorial control, 1065, 1077, 1078f
combinatorial gene library, 316
Combined DNA Index System (CODIS), 289b, 289t
compactin, 786b–787b
comparative genomics, 36, 317, 318f
- closest biological relatives of humans, 329–331, 330f
- genes involved in disease, 331–333, 336f
- human history learned from, 333–335, 334b–335b, 336f
- protein function and, 317t
competitive inhibitor, 197, 197f, 198
complementarity, of DNA strands, 28–29, 29f, 271, 271f
complementary DNAs (cDNAs), 316, 316f, 320f, 990
complementary protein-ligand interactions, in immune system
- analytical procedures based on, 167–168, 168f
- antibody binding to antigens, 165–168, 166f, 168f
- immune response cells and proteins, 164–165
complementary strands, 271
Complex I, 665, 665t, 666–667, 666f, 672f
Complex II, 665t, 666f, 667–668, 667, 667f, 672f
Complex III, 665t, 666f, 668f, 668–669, 669f, 672f
Complex IV, 665t, 666f, 669, 670–671, 670f, 672f
- in hypoxic conditions, 688
complex transposons, 952
Complex V. See ATP synthase
computational biochemistry, 138b–139b
concentration gradient, active transport against, 391–392, 391f
concerted inhibition, 814
concerted model, 158, 160f
condensation, 81
condensation reaction. See also Claisen condensation
- peptide bond formation by, 81, 81f
condensins, 908, 908f, 909f
cone cells, GPCR signaling in, 429f, 430b, 430f
configuration, 14–18, 15, 15f, 16f
- of biomolecules, 14–18
conformation(s), 18, 18f, 108
- of allosteric enzymes, 214–215, 214f, 215f
- of ATP synthase β units, 678–680, 679f
- ATP-driven changes in, 483
- of biomolecules, 14–18, 18f
- of DNA, 272–273, 272f, 273f
- of GLUT1, 388, 389f
- of hemoglobin, 153, 155f, 156f, 157, 160f
- in homopolysaccharides, 243–244, 243f, 244f
- induced fit changes in, 186
- of proteins, 29
  - weak interactions stabilizing, 107–108
- of pyranose ring, 235, 236f
congenital hyperinsulinemia, 862
congenital malformations, vitamin A deficiency causing, 357–358
conjugate acid-base pair, 57, 57f
- as buffers, 59–63, 60f, 62f
conjugate redox pair, 489
conjugated dienes, lipidic, 360
conjugated proteins, 83, 83t
consensus sequences, 96, 98b, 98f, 414–415, 963
- for E. coli promoters, 1056f
- of PKA protein substrates, 414–415
- of PKC protein substrates, 425
- for protein kinases, 219, 219t
- in transcription, 963, 964f
conservation of energy, 466
constitutive gene expression, 1056
contigs, 293
contraceptives, mifepristone, 445
contraction
- ATP energy for, 483, 487
- motor proteins involved in
  - interactions of, 170–172, 172f
  - myosin and actin, 169, 170f
  - proteins organizing thin and thick filaments, 169–172, 171f
- muscle metabolism for, 852–855, 854f, 855f, 856b–857b
- regulation of, 171, 172f, 427
convergent metabolic pathways, 463
cooking oils, partial hydrogenation of, 345, 345f
Coomassie blue, 87f, 88
cooperative binding
- conformational changes in, 155–156, 156f, 160f
- hemoglobin and carbon monoxide, 158b–159b
- hemoglobin and oxygen, 155–156, 156f
- mechanistic models of, 158–160, 160f
- quantitative description of, 156–157, 160f
cooperativity, of signal transduction, 409, 410f
Corey, Robert, 109, 111–116
Cori, Carl F., 529b, 561b–562b, 565
Cori, Gerty T., 529b, 561b–562b, 565
Cori cycle, 529b, 533, 561b–562b
- in muscle, 854, 855f
Cornforth, John, 775
Coronary Primary Prevention Trial, 786b
corrin ring system, 614b
corticotropin. See adrenocorticotropic hormone
corticotropin-releasing hormone, 845, 846f
cortisol, 845–846, 865
- as cholesterol derivative, 356, 356f
- phosphoenolpyruvate carboxykinase regulation by, 763, 763f
- stress signaling by, 865–866
cotransport systems, 391
- chloride-bicarbonate exchanger, 389–392, 391f
- ion gradients providing energy for, 398–399, 400f
- ${Na}^{+} K^{+}$ ATPase as, 392–394, 393f, 394f
Coumadin. See warfarin
coumarins, 906b
coumermycin A1, 906b
covalent catalysis, 187
covalent modification, 214
- of acetyl-CoA carboxylase, 753, 753f
- of glutamine synthetase, 803–804, 804f
- of histones, 904b–905b, 1075–1077, 1076t
- of HMG-CoA reductase, 782, 782f
- of PDH complex, 593–594, 593f
- of regulatory enzymes, 216–217, 217f
  - in metabolic regulation, 500, 501f
COX. See cyclooxygenase
COX-1. See cyclooxygenase 1
COX-2. See cyclooxygenase 2
COX4-1, 688
COX4-2, 688
cpDNA. See chloroplast DNA
CpG sequences, methylation of, 283
CPT1. See carnitine palmitoyltransferase 1
CPT2. See carnitine palmitoyltransferase 2
Crassulaceae, photosynthesis in, 732
CRE. See cAMP response element
creatine, 819
- biosynthesis of, 819–820, 821f
- in muscle, 854, 854f, 856b–857b
creatine kinase, 487, 637b
- in muscle, 854, 854f, 856b–857b
- tissue-damage assays using, 637b
creatine phosphate. See phosphocreatine
creatinine, 856b–857b
CREB. See cAMP response element binding protein
Creutzfeldt-Jakob disease, 134b–135b
Crick, Francis, 91, 117, 883, 1005, 1006f
- DNA structure of, 268–272, 271f, 272f, 915
- RNA world hypothesis proposed by, 998
- wobble hypothesis of, 1010–1012, 1012f, 1012t
CRISPR/Cas systems, 317t, 322–324, 323f, 325, 325b, 326f
cristae, 660
crocodiles, lactic acid fermentation by, 529b
cross talk, among signaling systems, 438, 438f
crossing over, 945f, 946
- errors in, 946b
CRP. See cAMP receptor protein
cruciform, 273
- in DNA, 274f
cruciform DNA, 895, 895f
crude extract, 84
cryo-electron microscopy (cryo-EM), 139–142, 140, 141f
crystalline substances, entropy of dissolving, 47, 47f
CTD. See carboxyl-terminal domain
C-terminal residue. See carboxyl-terminal residue
CTF1, 1081–1083, 1082f
CTP. See cytidine triphosphate
curvature, of membranes, biological processes using, 382–383, 383f, 384f
Cushing disease, 866
cyan fluorescent protein (CFP), 416b–417b
cyanide, 667t
cyanobacteria, 6
- phosphorylation/photophosphorylation in, 718, 718f
- photosynthetic membranes of, 718f
- reaction center of, 707
cyanocobalamin, 614b
cyclic AMP. See adenosine $3', 5' -cyclic monophosphate$
cyclic electron flow, 713
cyclic electron transfer, 708, 709f
cyclic GMP. See guanosine $3', 5' -cyclic monophosphate$
cyclic GMP phosphodiesterase (cGMP PDE), 423b
- in vision signaling, 429–431, 429f, 430b, 430f
cyclic nucleotide phosphodiesterase, 417
- cAMP hydrolysis by, 415f, 417
cyclic photophosphorylation, 713
cyclin, 447
- CDK regulation by, 447, 448f, 449f
- controlled degradation of, 447–449, 449f
- growth factor regulation of, 448, 449f
cyclin-dependent protein kinase (CDK), 447
- cell cycle regulation by
  - oscillating CDK levels in, 447, 447f, 448f, 449f
  - protein phosphorylation in, 449–450, 450f
- growth factor regulation of, 448, 449f
- inhibition of, 450
  - for cancer treatment, 452b–453b
cycloheximide, 1040, 1040s
cyclooxygenase (COX), 755
- in prostaglandin and thromboxane synthesis, 755, 758–759, 758f
cyclooxygenase 1 (COX-1), 758
cyclooxygenase 2 (COX-2), inhibition of, 355–356, 355f, 758, 758f
cycloserine, 820
cystathionine β-synthase, 808
cystathionine γ-lyase, 808
cysteine, 74s, 76, 76f, 644, 808
- biosynthesis of, 806–809, 809f
- catabolism of, 640f, 644–647, 644f, 646t
- in general acid-base catalysis, 187f
- properties and conventions associated with, 73t
cystic fibrosis (CF), 1049
- defective ion channel in, 397b–398b
- protein misfolding in, 135
cystic fibrosis transmembrane conductance regulator (CFTR) protein, 135, 396, 397b–398b
cystine, 76
cytidine, 266s
cytidine diphosphate (CDP), in phospholipid synthesis, 764f, 765
cytidine triphosphate (CTP)
- as chemical energy carrier, 294
- pyrimidine biosynthesis regulation by, 829, 829f
cytidylate (CMP), 265t, 486
- biosynthesis of, 827, 828f
- degradation of, 833–835, 834f, 835f
cytidylate synthetase, 828f, 829
cytochrome $b_{6} f$ complex, 709, 709f, 710, 714f, 718f
- cyclic electron flow with, 713
- dual roles of, 718, 718f
- PSI and PSII link with, 712–713
cytochrome $b c_{1}$ complex, 666f, 668, 668f, 669, 669f
- in cyanobacteria, 718, 718f
- of purple bacteria, 707, 708f
cytochrome c
- composition of, 82, 82t, 83t
- in mitochondrial respiratory chain, Complex II electron transfer to, 665t, 666f, 667–668, 668f, 669, 669f
- in mitochondrial triggering of apoptosis, 691, 692f
- residues, 123t
cytochrome $c_{6},$ dual roles of, 718, 718f
cytochrome f, water chain in, 51, 51f
cytochrome oxidase, 665t, 666f, 669, 670–671, 670f
cytochrome P-450 family, 690, 756b
- endoplasmic reticulum oxygenases, 690–691
- monooxygenases, 756b–757b
- steroid synthesis by, 690–691, 690f, 691f, 757b
cytochromes, 663
- in mitochondrial respiratory chain, 663–664, 663f, 664t
cytoglobin, function of, 149
cytokines, 165
- cell cycle regulation by, 448, 449f
cytoplasm, 2, 2f, 6–8
- cytoskeleton organization of, 6–8, 8f
cytosine (C), 264, 264s, 265t
- base pairing of, 269f
- biosynthesis of, 827, 828f
- deamination of, 280, 281f
- degradation of, 833–835, 834f, 835f
- methylation of, 283
cytoskeleton, 6–8, 7f, 8f
- of eukaryotic cells, 6–8, 8f
cytosol, 2, 371f
- acetate shuttling to, 751–752, 752f
- fatty acid synthesis in, 750–751, 751f
- sucrose synthesis in, 733–734, 733f
cytotoxic T $(T_{C})$ cells, 165

D

d, l system, 72, 72f
- in monosaccharide nomenclature, 232, 232f
D arm, 1019f, 1020
$Δ^{3}$ , $Δ^{2}$ -enoyl-CoA isomerase, 611, 612f
dalton, 13b
Dalton, John, 430b
Dam methylase, 923t, 924
- in mismatch repair, 931
Darwin, Charles, 30, 1092b
David, Jacques Louis, 465
Davies, H. W., 56b
Dayhoff, Margaret Oakley, 71
DBRP. See destruction box recognizing protein
DCC gene, mutations in, 455
DCCD. See dicyclohexylcarbodiimide
dCDP. See deoxycytidine diphosphate
DDI. See dideoxyinosine
ddNTPs. See dideoxynucleoside triphosphates
de novo pathways, 823
- of nucleotide biosynthesis, 823–824
  - purines, 825–827, 825f, 826f
  - pyrimidines, 827, 828f, 829f
deacylation, in chymotrypsin mechanism, 204–208, 204f, 205f, 206f–207f
deamination, of nucleotides, 280–283, 281f, 282f
debranching enzymes, 559
- glycogen breakdown by, 558, 558f, 559f
decarboxylations, 473, 474f
deep sequencing, 291
degenerate codons, 1009, 1012t
dehydration
- in fatty acid synthesis, 748, 749f
- of 2-phosphoglycerate, 13f, 520–521
dehydrogenases, 477b, 489
- in mitochondrial respiratory chain, 660–662, 662t
- NADH and NADPH actions with, 493–494, 493f
- in oxidation-reduction reactions, 476
dehydrogenation, 489
- in biological oxidations, 477f, 489–490
- in oxidation-reduction reactions, 476
dehydrohydroxylysinonorleucine, 120s
deletion mutation, 930, 952f
denaturation, 129
- of nucleic acids, 278–280, 279f, 280f
- of proteins, 128–136, 129f
  - loss of function with, 129–130, 129f
  - renaturation after, 130, 130f
denaturation mapping, 916
dendrotoxin, 444
Denisovans, 333, 336f
denitrification, 795, 795f
deoxyadenosine, 266s
5′-deoxyadenosyl group, 614b
5′-deoxyadenosylcobalamin, 613, 614b, 615b
deoxyadenylate, 265t
deoxycytidine, 266s
deoxycytidine diphosphate (dCDP), thymidylate synthesis from, 833, 833f
deoxycytidylate, 265t
2-deoxy-d-ribose, 230s
2′-deoxy-d-ribose, in DNA, 264–265
2-deoxyglucose, for cancer treatment, 527b–528b
deoxyguanosine, 266s
deoxyguanylate, 265t
deoxyhemoglobin, 155, 155f
- BPG binding to, 161, 162f
- structure of, 128f
deoxyribonucleic acid (DNA), 13, 28, 263
- amplification of
  - with cloning vectors, 304–309, 306f, 307f, 308f
  - PCR, 283–286, 285f, 288b–289b, 314–315, 315f
- in bacteria, 887, 888f, 888t, 909–910, 910f
- chemical synthesis of, 283, 284f
- chloroplast, 887
- chromosomal packaging of. See chromosomes
- cloning of. See DNA cloning
- closed-circular, 892
- complementary, 316, 316f, 318f, 320f, 990
- cruciform, 895, 895f
- damaged. See DNA repair; mutations
- degradation of, 916
- denaturation and annealing of, 278–280, 279f, 280f
- denaturation mapping of, 916
- double-strand break in, 940–948, 941f
- of E. coli, 28f
- in eukaryotes, 887–890, 888t, 889f
- exon transcription from, 973
- footprinting of, 965b
- genetic continuity and, 28
- intron transcription from, 973
- linear sequence of, 29–30, 29f
- melting point of, 278–280, 280f
- methylation of, 283
- mitochondrial, 887, 889f
- mutation of. See mutations
- nitrogenous bases of. See nitrogenous bases
- noncoding, 328
- nonenzymatic transformations of, 280–283, 281f, 282f
- nontemplate strand of, 962, 962f
- phosphodiester linkages in, 267–268, 267f
- polymerase chain reaction (PCR), 917f
- proteins encoded by, 29–30, 29f
- recombinant. See recombinant DNA
- relaxed, 891, 893f
- replication of, 272f
- RNA polymerase binding to, 1055–1056, 1055f
- satellite, 890
- sequencing of
  - Sanger method for, 287–290, 287f, 290f
  - technologies for, 290–293, 292f, 293f
- site-specific recombination, 940
- strand rotation of, 962
- structure of, 28–29, 29f
  - double helix, 270–272, 271f, 272f
  - nucleotide base effects on, 268, 269f
  - unusual, 273–274, 273f, 274f, 275f
  - unwinding of, 916, 916f
  - variation in, 272–273, 272f, 273f
- study of. See genomics
- supercoiling of, 891, 891f, 892f
  - linking numbers describing, 893–895, 894f
  - plectonemic and solenoidal, 898, 898f
  - replication and transcription and, 891, 892f
  - topoisomerases changing, 895–898, 895f, 896f, 897f, 897t, 906b
  - underwinding of, 892–895, 893f, 894f, 895f
- transcription of. See transcription
- underwinding of, 892–893, 893f
  - linking numbers measuring, 893–895, 894f
  - topoisomerases changing, 895–898, 895f, 896f, 897f, 897t, 906b
- uracil in, 833
- UV light absorption by, 279
- in viruses, 885f, 886–887, 887t, 929–930
deoxyribonucleotides, 29, 265, 266s
- biosynthesis of, 829–832, 830f, 831f, 832f
deoxythymidine, 266s
deoxythymidylate, 265t
deoxyuridine monophosphate (dUMP), thymidylate synthesis from, 833, 833f, 837f
dephosphorylation, 586f
- of glycogen synthase, 567, 567f, 568f
- in metabolic regulation, 501, 501f
depolarization, of neurons, 443–444, 444f
depurination, of nucleotides, 281, 281f
dermatan sulfate, 245
desaturation, of saturated fatty acids, 754–755, 755f, 756b–757b
desensitization, 409
- of β-adrenergic receptors, 418–419, 419f
- in signal transduction, 409, 410f
designer proteins, 138b–139b
desmosine, 76, 77s
desolvation, 186
- by enzymes, 186
desphosphorylation, 477b
destruction box recognizing protein (DBRP), 448, 449f
development
- evolution link to, 1092b–1093b
- regulatory protein cascades in, 1087–1089, 1087f, 1088f, 1089f, 1090f
dexamethasone, phosphoenolpyruvate carboxykinase regulation by, 763, 763f
dextrans, 246
- glycosidic bond in, 244f
- structures and roles of, 247t
dextrinases, 523
dextrins, in feeder pathways for glycolysis, 523
dextrose, 229
DFMO. See difluoromethylornithine
$Δ G$ . See free-energy change
$Δ G^{‡}$ . See activation energy
$Δ G °$ . See standard free-energy change
$Δ G' °$ . See biochemical standard free-energy change
$Δ G_{B}$ . See binding energy
DGDGs. See digalactosyldiacylglycerols
$Δ G p$ . See phosphorylation potential
DH. See β-hydroxyacyl-ACP dehydratase
DHA. See docosahexaenoic acid
DHAP. See dihydroxyacetone phosphate
diabetes mellitus, 875
- acidosis in, 63–64, 63f, 620–621, 877
- blood glucose measurements in, 238b–239b
- fuel metabolism in uncontrolled, 863–864, 864t, 865f, 866f
- insulin defects causing, 875–877
- insulin treatment, 876b
- ketone body production in, 620–621, 620f, 877
- mitochondrial defects causing, 695–696, 696f
- neonatal, 862
- protein misfolding in, 133
- triacylglycerol synthesis in, 760, 761f
- type 1. See type 1 diabetes mellitus
- type 2. See type 2 diabetes mellitus
diacylglycerol, 425
- as intracellular signal, 354
- as second messenger, 425, 425t, 427f
diacylglycerol 3-phosphate, 348f, 760
- glycerophospholipids as derivatives of, 348f
- synthesis of, 760, 761f
dialysis, 84
diastereomers, 16, 16f
diazotrophs, nitrogen fixation by, 797–802, 797f, 800f, 801f
Dicer, 986, 986f
dichloroacetate, pyruvate dehydrogenase kinase inhibition by, 594
2,6-dichlorophenolindophenol, 702–703, 703s
dicyclohexylcarbodiimide (DCCD), 667t
dideoxy chain-termination sequencing. See Sanger sequencing
dideoxyinosine (DDI), 991b
dideoxynucleoside triphosphates (ddNTPs), in DNA sequencing, 286, 287f, 290, 290f
Diels-Alderase, 138b–139b
2,4-dienoyl-CoA reductase, 612, 612f
diet
- body mass regulation by, 871–872, 871f, 872f
- type 2 diabetes mellitus management with, 878–879, 879t
dietary fats, absorption of, 602–603, 602f
dietary protein, enzymatic degradation of, 627–628, 628f
differentiation, cellular, 1091f
diffusion, 3
- cellular dimensions and, 3, 3f
- of membrane lipids
  - flip-flop, 378–379, 378f
  - hop, 379, 379f
  - lateral, 378f, 379–380, 379f, 380f
- of solutes across membranes, 385f, 386, 386f
difluoromethylornithine (DFMO), 201b–202b
DIFP. See diisopropylfluorophosphate
digalactosyldiacylglycerols (DGDGs), 349f
digestion
- of fats, 602–603, 602f
- of proteins, 627–628, 628f
dihedral angles, of protein secondary structures, 114–116, 115f
dihydrobiopterin reductase, 649, 649f
dihydrofolate reductase, 183f, 833
- inhibition of, 836, 836f, 838
- in thymidylate synthesis, 833, 833f
dihydrolipoyl dehydrogenase, 576, 577f
- substrate channeling of, 578, 578f
dihydrolipoyl transacetylase, 576, 577f
- substrate channeling of, 578, 578f
dihydroorotase, 828, 828f
dihydroorotate dehydrogenase, 671
- electron transfer by, 671, 672f
dihydrouridine, 983f
dihydroxyacetone, 230, 230s, 233s
dihydroxyacetone phosphate (DHAP), 516
- in Calvin cycle, 721, 723f, 724f
  - $P_{i} -triose$ phosphate antiport system and, 724–725, 725f, 726f
- in glycolytic pathway, 512f, 513, 513f, 516, 517f, 519f
- in sucrose synthesis, 733, 734f
- in triacylglycerol and glycerophospholipid synthesis, 760, 761f
diisopropylfluorophosphate (DIFP), 200f
dimers, pyrimidine, 281, 282f
dimethylallyl pyrophosphate, 774
- in cholesterol synthesis, 774, 774f
dimethyllysine, 1038f
dimethylsulfate, 282, 282f
dinitrogenase, 797–802, 797f, 800f
dinitrogenase reductase, 216, 797–802, 797, 797f, 800f
2,4-dinitrophenol (DNP), oxidative phosphorylation uncoupling by, 667t, 676, 676f
dioxygenases, 477b, 756b
diphtheria toxin, 1040
dipole, of a helix, 113, 113f
direct protein sequencing, 92, 92f
direct transposition, 952–953, 953f
disaccharides, 229
- energetic conformations of, 244f
- in feeder pathways for glycolysis, 522f, 523–525
- formation of, 237f
- glycosidic bond in, 237–238, 240f, 240t
- nomenclature of, 239–240, 240f, 240t
dissociation constant $(K_{d}),$ 150–151, 150f, 151t, 152, 192, 197f
- of ES complex, 192
- for myoglobin and oxygen, 150f, 152
distal His, 152, 153
disulfide bonds, 76f, 93f
disulfide cross-links, posttranslational formation of, 1039
divergent evolution, 584
divergent metabolic pathways, 463
divergent signaling pathways, 409
divicine, 548b
DNA. See deoxyribonucleic acid
DNA cloning, 302
- gene isolation by, 302
- PCR adaptations for, 314–315, 315f
- protein production using
  - altered genes and proteins, 312–313, 312f
  - bacteria systems used for, 310, 310f
  - expression vectors for, 309, 310f
  - insect and insect virus systems used for, 311–312, 311f
  - mammalian cell systems used for, 312
  - tags for purification of, 313–314, 313t, 314f
  - yeast systems used for, 310–311
- restriction endonuclease and DNA ligase in, 302–304, 303f, 303t, 304t, 305f
- steps of, 302
- vectors, 302
  - BACs, 307, 308f
  - expression, 309, 310f
  - plasmids, 305–306, 306f, 307f
  - YACs, 307–309
DNA genotyping, 288b, 289b
DNA glycosylases, 934
DNA gyrase, 923t, 926t
DNA helicase II, 934
DNA library, 315–316
- protein function study using, 315–316, 316f, 320f
DNA ligases, 303, 494, 922, 926t
- in mismatch repair, 934
- reaction mechanisms of, 927f
- recombinant DNA from, 302–304, 303f, 303t, 304t, 305f
DNA metabolism. See also DNA recombination; DNA repair; DNA replication
- nomenclature of, 915–916
- overview of, 915–916, 915f
DNA microarrays, 322f
DNA photolyases, 931t, 937, 937f
DNA polymerase α, 929
DNA polymerase β, 940
DNA polymerase δ, 929
DNA polymerase ε, 929
DNA polymerase η, 940
DNA polymerase ι, 940
DNA polymerase I, 916
- discovery of, 916
- functions of, 919, 926t
- large (Klenow) fragment of, 920
- in nick translation, 920, 920f
DNA polymerase II, 919, 920t
DNA polymerase III, 919, 920, 920t
- in elongation, 924, 926f
- functions of, 926t
- in mismatch repair, 934
- subunits of, 921f, 921t
DNA polymerase IV, 920t, 940
DNA polymerase λ, 940
DNA polymerase V, 920t, 940
DNA polymerases, 283, 916
- in base-excision repair, 940
- dissociation and reassociation of, 920
- in DNA sequencing, 287–290, 287f, 290f
- $5'\to 3'$ exonuclease activity of, 920, 920f
- functions of, 919–921, 926t
- in nick translation, 920, 920f
- in PCR, 283–286, 285f
- primer in, 917, 918f
- processivity of, 919
- proofreading by, 917–919
- properties of, 920t
- reaction mechanisms of, 918f
- in recombinant DNA technology, 303t
- in replication. See also DNA replication
  - in bacteria, 915–930
  - in eukaryotes, 929
- RNA-dependent. See reverse transcriptases
- template for, 917, 918f
- $3'\to 5'$ exonuclease activity of, 917–919
- types of, 919–921, 920t, 921t
- viral, 929–930
DNA primases, 922, 923t, 924, 924f, 926t
DNA recombination
- in bacteria, 941–943, 941f, 942f, 943f
- branch migration in, 942, 942f, 943f
- in DNA repair, 941–943, 941f
- double-strand break repair model for, 947–948
- in eukaryotes, 944–948, 944f, 945f
- functions of, 940–941
- homologous genetic, 940–948
  - bacterial, 941–943, 941f, 942f, 943f
  - double-strand break initiation of, 947–948
  - functions of, 940–941, 947
  - during meiosis, 944–948, 944f, 945f
- nonhomologous end joining, 948–950, 950f
- site-specific, 940, 950–951, 951f, 952f
- transposition, 940
DNA repair, 29, 29f, 930–940
- in bacteria, 931t
- base-excision, 931t, 934–935
- cancer and, 932b
- direct, 937–938
- DNA photolyases in, 931t, 937–938, 937f
- initiation of, 948b–949b
- mismatch, 917–919, 931–934, 931t, 933f, 934f, 935f
- nick translation in, 920, 920f
- nucleotide-excision, 931t, 932b, 935–937, 936f
- $O^{6} -methylguanine-DNA$ methyltransferase in, 938f, 939f
- proofreading in, 917–919
- recombination in, 941–943, 941f
- recombinational, 941, 952f
- SOS response in, 939
DNA replicase system, 921
DNA replication, 28–29, 29f
- accuracy of, 917–919, 919f
- in bacteria, 915–930
- base pairing in, 917, 918f, 919f
- base stacking in, 917, 918f
- chain elongation in, 918f, 924, 924f–926f, 927
- crossing over in, 945f, 946
- directionality of
  - in bacteria, 916, 916f
  - in eukaryotes, 929
- DNA damage and, 939f
- DNA-binding proteins in, 922, 923t
- elongation, 924–926
- enzymes and protein factors, 921–922
- enzymology of, 918f. See also DNA polymerases
- error-prone translesion, 932b, 938–940, 939f
- in eukaryotes, 927–929, 929f
- helicases in, 921–922, 923f, 923t
- in immunoglobulin genes, 953–955, 954f, 955f
- initiation of, 922–924, 923f, 923t
- lagging strand in, 916, 916f
  - synthesis of, 924, 924f, 925, 925f, 926f
- leading strand in, 916, 916f
  - synthesis of, 924, 924f, 925, 925f
- mistakes in, 917–919
- nick translation in, 920, 920f
- nucleophilic attack in, 917, 918f
- Okazaki fragments in, 916, 916f
  - synthesis of, 924–925, 924f, 926f
- origin-independent restart of, 943
- overview of, 915–916
- phosphorylation in, 918f
- primer in, 917, 918f, 922
- proofreading in, 917–919
- replication fork in, 916, 916f, 924
  - in bacteria, 916, 916f, 924, 924f, 925f
  - in eukaryotes, 928–929
  - repair of, 941–943, 941f
- replisomes in, 920, 925
- rules of, 915–916, 916f
- semiconservative, 915
- strand synthesis in, 916, 916f
- supercoiling in, 891, 892f
- template for, 915, 917, 918f
- Ter sequence in, 927, 927f
- termination of, 926–927, 927f, 928f
- topoisomerases in, 922
- transcription compared with, 961
- transposition in, 951–953, 953f
- Tus-Ter sequence in, 927, 927f
- visualization of, 915f
DNA replication origin, 916
- in bacteria, 916, 916f
DNA sequencing technologies, 290–293
- advances in, 290–293, 292f, 293f
- footprinting, 965b
DNA synthesis, RNA-dependent, 987, 1090f
- retroviruses in cancer and AIDS, 990–991, 990f, 991b
- by reverse transcriptases, 988–990, 989f
- similarity of transposons and introns to retroviruses, 990f, 991–993, 991f
- telomerase as specialized reverse transcriptase, 993, 994
DNA transposition, 940
DNA unwinding element (DUE), 922
DNA viruses, 929–930
DnaA protein, 922, 923f, 923t
DnaB helicase, 943
- in replication elongation, 924, 924f, 925f, 926f, 926t
- in replication initiation, 923, 923f, 923t
DNA-binding activators, in transcription factor assembly, 1077–1080, 1079f, 1080f
DNA-binding domains, of regulatory proteins, 1060–1063, 1060f, 1061f, 1062f, 1063f
DNA-binding proteins, 922, 923f
DnaC protein, 943
- in replication initiation, 923f, 923t
DNA-dependent RNA polymerase, 961, 962, 962f
DnaG protein. See primase
DNA-PKcs, 949, 950f
DNases, 916
DnaT protein, 943
DNP. See 2,4-dinitrophenol
docosahexaenoic acid (DHA), 343, 754
- synthesis of, 754, 754f
dolichols, 359f, 360
domains, 3, 4f, 123
- DNA-binding, 1060–1063, 1060f, 1061f, 1062f, 1063f
- of globular proteins, 123–124, 123f, 124f, 125f
- of living organisms, 3, 4f
- protein-protein interaction, 1063–1065, 1064f
- of transcription activators, 1081–1083, 1082f
dopamine, 821, 823f
double bonds, in fatty acids, 341–343
double helix
- DNA, 270–272, 271f, 272f
  - denaturation and annealing of, 278–280, 279f, 280f
  - unwinding of, 916, 916f
- RNA-DNA, 961, 962f
double-displacement mechanism, 194–195, 194f, 195f
double-reciprocal plot, 191f
double-strand break repair model, 947, 948
Down syndrome, 946b
doxorubicin (Adriamycin), 906b
- tumor resistance to, 396
driver mutations, 455
Drosha, 986, 986f
Drosophila melanogaster, developmental regulation in, 1087–1089, 1087f, 1088f, 1089f, 1090f
drugs, P-450 enzyme metabolism of, 691, 756b–757b
DUE. See DNA unwinding element
dulaglutide (Trulicity), 879t
dUMP. See deoxyuridine monophosphate
Duve, Christian de, 6, 562b
dynamic steady state
- of living organisms, 19–20, 497–498
- maintenance of, 497–498
dynamin, 1047f, 1047
dysentery, 256

E

ε. See elasticity coefficient
E. See reduction potential
E site. See exit site
E°. See standard reduction potential
E2F, in cell cycle regulation, 448, 449f, 450
eastern skunk cabbage, 685b
eating behavior. See feeding behavior
E.C. number. See Enzyme Commission number
ECM. See extracellular matrix
Edelman, Gerald, 165
Edman, Pehr, 92
Edman degradation, 92
effectors, 1057
EFT:ubiquinone oxidoreductase, 607
EGFR. See epidermal growth factor receptor
Ehlers-Danlos syndrome, 120, 251b
eicosanoids, 355–356
- formation of, 755, 758–759
- signaling role of, 355–356, 355f
- synthesis of, 755, 758–759, 758f, 759f
eicosapentaenoic acid (EPA), 343, 355, 754
- synthesis of, 754
eicosatetraenoate. See arachidonate
electric charge
- of amino acids, 79
- in chlorophyll, 707, 707f
electrical measurement, of ion channel function, 401, 401f
electrical signaling, by gated ion channels, 442–443, 443f
electrochemical gradient, 385, 385f
- active transport against, 391–392, 391f
electrochemical potential, 385, 385f
electrogenic transport, 394
electromagnetic radiation, 703, 703f
electromotive force (emf), 488
electron affinity, reduction potentials as measures of, 490–492, 491f, 491t
electron carriers
- for cellular glucose oxidation, 492
- coenzymes and proteins serving as, 492–494
- in mitochondrial respiratory chain, 662–665, 663f, 664f, 664t, 665f
  - Complex I, 665–667, 665t, 666f
  - Complex II, 665t, 666f, 667–668, 667f
  - Complex III, 665t, 666f, 668–669, 668f, 669f
  - Complex IV, 665t, 666f, 669–671, 670f, 688
  - in respirasomes, 671, 671f
- NADH and NADPH as, 493–494, 493f
electron density maps, 136–137
electron flow
- in chlorophylls, 706f, 707f
  - thermodynamics of, 709
- in chloroplasts, 701–704
- cyclic, 713
- through cytochrome $b_{6} f$ complex, 712–713, 712f
- in Fe-S reaction center, 711
- noncyclic, 713
- in pheophytin-quinone reaction center, 708, 708f
- in photosynthesis, 701–704, 702f, 703f
- in photosystem I, 711, 712f
- in photosystem II, 710, 712f
- proton gradient and, 716, 716f
- in respiratory chain, 672f
electron transfer
- in biological oxidation-reduction reactions, 477f, 478, 488
  - dehydrogenases involved in, 493–494, 493f
  - dehydrogenation, 477f, 489–490
  - electron carriers in, 493–494, 493f
  - flavin nucleotides in, 495–496, 495f
  - free-energy change of, 491t, 492
  - half-reactions describing, 489
  - ${NAD}^{+}$ functions outside of, 494–495
  - NADH and NADPH in, 493–495, 493f, 495f
  - niacin deficiency and, 494, 495f
  - oxidation of glucose to ${CO}_{2}$ , 492
  - reduction potentials for, 490–492, 491f, 491t
  - work provided by electron flow in, 488–489
- energy from, 21
- inhibition of, 667t
- in nitrogen fixation, 800, 800f
- in oxidation-reduction reactions, 488
- in oxidative phosphorylation, 659–660, 660f
  - ATP synthesis coupling to, 675–677, 675f, 676f, 677f
  - by mitochondrial respiratory chain. See mitochondrial respiratory chain
- in photosystem II, 710f
electroneutral exchange, 391
- by chloride-bicarbonate exchanger, 389–392, 391f
electrons, citric acid cycle production of, 587–589, 589t
electron-transferring flavoprotein (ETF), 607, 608f
- electron transfer by, 671, 672f
electrophiles, 207f, 473
- biological, 473, 473f
electrophoresis, 87
- of proteins, 87–89, 87f, 89f
- pulsed field, 309
electroporation, 306
electrospray ionization mass spectrometry (ESI MS), 94, 94f
electrostatic interactions
- of charged solutes, 46, 46t, 47f, 50t
- homopolysaccharide folding and, 243–244, 244f
- in membrane protein attachment, 372
- protein stability and, 108–109
elements, chemical, 10, 10f
elexacaftor, 398b
elimination reactions, 474, 475f
- standard free-energy changes of, 469t
Elion, Gertrude, 836, 838, 929
ELISA. See enzyme-linked immunosorbent assay
Elk1, in INSR signaling, 434f, 435
ELL protein, 969t, 970f
ellipticine, 906b
elongation, 1030
- in protein synthesis, 1015, 1016f, 1016t, 1030–1035
  - aminoacyl-tRNA binding, 1030–1031, 1031f
  - peptide bond formation, 1031–1032, 1032f
  - proofreading during, 1034–1035
  - translocation, 1032–1034, 1034f
elongation factors, 969–970, 1030, 1031f, 1032–1034, 1034f
elongin (SIII), 969t, 970f
Elvehjem, Conrad, 494
EM. See electron microscopy
embryo, developmental regulation in, 1087–1089, 1087f, 1088f, 1089f, 1090f
embryonic stem cells, 1091
EMDataResource, 141
emf. See electromotive force
enantiomers, 16, 16f, 17, 17b, 71, 232
- amino acids as, 71, 72f
- monosaccharides as, 232, 232f
encephalomyopathies, mitochondrial, 695
ENCODE initiative, 328
endergonic reactions, 20, 467
Endo, Akira, 786b–787b
endocannabinoids, 873–874, 874f
endocrine hormones, 843
endocrine system, 842, 842f. See also hormones
- bottom-up signaling in, 846–847, 847f
- major glands of, 845, 846f
- top-down signaling in, 845–846, 846f, 847f
endocytosis, 8
- of cholesteryl esters, 781–782, 781f
- of proteins, 1046–1048, 1047f
endogenous pathway, 780
- of cholesterol transport, 779f, 780
endomembrane system, 7, 369–371, 370f
endonucleases, 916
- AP, 935
- in mismatch repair, 932–933
endoplasmic reticulum (ER), 6, 7f, 371f
- in endomembrane system, 370f
- membrane synthesis in, 369–370, 370f, 770
- P-450 enzymes of, 690–691
- posttranslational modification in, 1041–1042, 1041f, 1042f
- ribosomes on, 1007f
endoribonuclease, 987
endosymbiosis, 34–35, 35f
- eukaryote evolution through, 34, 35f, 692–693, 693f
endosymbiotic bacteria, chloroplast evolution from, 717–718, 718f
endothermic reactions, 467
endotoxin, 253
energy
- for active transport against concentration or electrochemical gradient, 391–392
- adenosine triphosphate and, 21, 21f
- chemical reaction changes in, 24–25, 26f, 180–181, 180f, 181f, 185, 185f
  - in biological systems. See bioenergetics
- conservation of, 466
- for creating and maintaining order, 21, 21f, 22b–23b
- from electron flow, 21
- nucleotides as carriers of, 294, 294f
- in photons, 703
- solar, 700, 701f
- sources of, 3–5, 4f
- storage of
  - in homopolysaccharides, 241–242, 242f
  - in triacylglycerols, 344–345, 344f
  - in waxes, 345–346, 346f
- transformations of, by living organisms, 20–21, 20f
energy coupling, 22–23, 24f
- oxidation and phosphorylation, 675–677, 675f, 676f, 677f
  - nonintegral stoichiometries of $O_{2}$ consumption and ATP synthesis in, 682–683
energy expenditure, regulation of. See body mass regulation
energy sources
- of living organisms, 3–5, 4f
- solar, 700, 701f
energy transductions, 466
Engelmann, T. W., 706f
enhancers, 1078, 1079f
enolase, 520
- in glycolytic pathway, 513f, 520
- mechanism of, 210, 211f
enoyl-ACP reductase (ER), 748, 749f
enoyl-CoA hydratase, 607, 608, 608f
Entamoeba histolytica, 256
enterohepatic circulation, 779f, 781
enteropeptidase, 628
enthalpy (H ), 20, 467
- in biological systems, 466–467
entropy (S), 20, 22b–23b, 467
- in biological systems, 466–467
- of dissolving crystalline substances, 47, 47f
- of enzyme-substrate complex, 49, 49f
- second law of thermodynamics and, 466–467
entropy reduction, 185–186
- by enzymes, 185–186, 186f
env gene, 989, 989f, 991, 992
enzyme activity. See activity
enzyme cascades, 409, 566
- in epinephrine and glucagon action, 566, 566f
- in GPCR signaling, 416, 418f
- in hormonal signaling, 843
- leptin triggering of, 869
- multivalent adaptor proteins involved in, 440, 441f
- in RTK signaling, 433f, 434–435, 434f
- in signal transduction, 409, 410f
Enzyme Commission number (E.C. number), 179
enzyme kinetics, 188
- allosteric enzymes, 215, 216f
- irreversible inhibition, 200–203, 200f, 201b–202b, 203f
- $k_{cat},$ 192, 193t
- $K_{m},$ 191, 191f
  - determination of, 194
  - enzyme comparisons using, 193–194, 193t
  - interpretation of, 192–193, 192t, 193t
  - metabolic regulation and, 499f, 500f
  - reversible inhibitor effects on, 198–199, 200t
- $V_{0},$ 188–190, 189f, 191f
- $V_{max},$ 189–191, 189f, 191f
  - allosteric enzymes, 215, 216f
  - determination of, 191
  - interpretation of, 192–193, 192t, 193t
  - reversible inhibitor effects on, 198–199, 200t
- Michaelis-Menten equation, 191, 191f
  - in bisubstrate reactions, 194–195, 194f
  - for competitive inhibitor, 197–198
  - for mixed inhibitor, 198
  - for uncompetitive inhibitor, 198
- pH effects on, 195–196, 196f
- pre-steady state, 196–197, 196f, 197f
- for reactions with two or more substrates, 194–195, 194f, 195f
- relationship between substrate concentration and reaction rate, 188–190, 189f
  - quantification of, 191–192, 191f
- reversible inhibition, 197–200, 200t
enzyme multiplicity, 814
enzyme-linked immunosorbent assay (ELISA), 168f
enzymes, 25, 147, 178. See also specific enzymes
- catalysis by, 25–27, 26f, 177, 179–188, 188f
  - acid-base, 186–187, 187f
  - at active site, 180, 180f
  - binding energy in, 183–186, 183f, 184f, 185f, 186f
  - covalent, 187
  - kinetics of. See enzyme kinetics
  - metal ion, 187–188
  - principles of, 182–183
  - reaction rate and equilibrium effects during, 180–182, 180f, 181f
  - regulation of, 498–501, 499f, 499t, 500f, 500t, 501f
  - specificity of, 182–183, 185, 186f
  - thermodynamics of, 182, 182t, 470–471
  - transition state role in, 183–186, 183f, 184f, 185f
- classification of, 179, 179t
- coenzymes of, 2, 178–179
  - adenosine in, 294–295, 295f
  - as electron carriers, 492–494
  - examples of, 178t, 179t
- cofactors of, 178, 478
  - adenosine in, 294–295, 295f
  - in amino acid degradation, 628–630, 629f, 630f, 641–644, 641f, 642f, 643f
  - inorganic ions serving as, 178, 178t
  - lipids as, 359–360
- in DNA cloning and recombinant DNA creation, 302–304, 303f, 303t, 304t, 305f
- in DNA replication, 921–922
- historical study of, 178
- inhibition of, 197, 197f
  - by antibiotics, 210–211, 212f, 213f
  - irreversible, 200–203, 200f, 201b–202b, 203f
  - by protease inhibitors, 208–209, 208f, 209f
  - reversible, 197–200, 200t
- mechanisms of
  - antibiotics based on, 210–211, 212f, 213f
  - chymotrypsin, 204–208, 204f, 205f, 206f–207f
  - enolase, 210, 211f
  - hexokinase, 209–210, 210f
  - lysozyme, 210–213
  - protease inhibitors based on, 208–209, 208f, 209f
  - representation of, 207f
- moonlighting, 584b–585b
- nomenclature for, 179, 179t, 477b, 586f
- overview of, 177–179
- pH optimum of, 63, 63f
- as proteins, 178–179
- quantification of, 89–90, 90f
- receptor. See receptor enzymes
- regulation of, 498–501, 499f, 499t, 500f, 500t, 501f
- regulatory. See regulatory enzymes
- RNA. See ribozymes
enzyme-substrate (ES) complex, 188f
- active site in, 180, 180f
- entropy of, 49, 49f
- $K_{d}$ of, 192
- rate effects of, 188–190, 189f
  - quantification of, 191–192, 191f
- weak interactions in
  - binding energy from, 183
  - specificity from, 185, 186f
  - transition state optimization of, 183–184, 183f, 184f, 185f
EPA. See eicosapentaenoic acid
epidermal growth factor receptor (EGFR), 437, 438f
- oncogenes encoding, 452b–453b
epigenetic information, 904b
- in histone variants, 904b–905b
epimers, 232, 232f
epinephrine, 413s, 821, 842
- β-adrenergic receptor response to
  - cAMP as second messenger in, 412–413, 414f, 415f, 418f, 420, 421f
  - desensitization of, 418–419, 419f
  - termination of response by, 416–418
- amplification of signaling by, 843
- biosynthesis of, 821, 823f
- cells responding to, 411
- fuel metabolism regulation by, 864–865, 866t
- in global regulation of carbohydrate metabolism, 568–570, 569f, 570f
- glycogen phosphorylase regulation by, 565f, 566, 566f
- insulin cross talk with, 438, 438f
- triacylglycerol mobilization by, 603, 604f
- triacylglycerol synthesis regulation by, 762
epitope, 165
epitope tags, 320
- for immunoprecipitation, 320–321, 321f
equilibrium, 19–20, 22
- enzymes effects on, reaction rate effects compared with, 180–182, 180f, 181f
- metabolic regulation and, 501–502, 502t
- thermodynamic definition of, 182, 182t
equilibrium constant $(K_{eq}),$ 23–25, 54, 182
- denotation of, 150
- free-energy change relationship to, 182, 182t, 468–470, 468t, 469t
- for ionization of water, 54–55
- $K_{a},$ 150, 150f
- $K_{d},$ 150–152, 150f, 151t
- of metabolic enzymes, 502t
- multiplicative nature of, 471
- thermodynamic definition of, 182, 182t
equilibrium expression, 150
- for reversible protein-ligand binding, 150–152, 150f, 151t
ER. See endoplasmic reticulum; enoyl-ACP reductase
ErbB, 452b–453b
Erbitux. See cetuximab
erectile dysfunction, PDE inhibitors for, 423b
ergosterol, 352
- synthesis of, 775, 776f
ERK, in INSR signaling, 434f, 435, 437f
erlotinib (Tarceva), 453b
error-prone translesion DNA synthesis, 932b, 938–940, 939, 939f
erythrocytes, 71f, 858, 858f
- anion exchangers of, 389–392, 391f
- aquaporins in, 400
- blood coagulation, 221f
- BPG in, 161
- carbonic anhydrase in, 160
- glucose transporters of, 387–389, 387f, 388f, 389f, 389t
- hemoglobin in, 153
- lectin role in degradation of, 254
- in sickle cell anemia, 162–164, 163f
erythromycin, 361f
erythrose, 233s
erythrose 4-phosphate
- amino acid biosynthesis from, 811, 811f, 814f
- in Calvin cycle, 723f
- in pentose phosphate pathway, 549, 549f, 550f
erythrulose, 233s
ES complex. See enzyme-substrate complex
Escherichia coli, 5
- ABC transporter of, 396
- chromosome of, 886, 888f, 888t, 909–910, 909f
- coordination of r protein and rRNA synthesis in, 1070–1071, 1070f, 1071f
- DNA cloning in, 302
- DNA of, 28, 28f, 909–910, 910f
- DNA replication in, 919–929
- expression vectors, 309, 310f
- genes of, 36
- genetic code expansion in, 1025b–1027b
- genetic map of, 915
- glutamine synthetase in, 802, 803f
- lactose metabolism in, regulation of, 1058–1060, 1058f, 1059f, 1066–1067, 1066f
- lipopolysaccharides of, 253
- metabolome of, 500f
- molecular components of, 12, 14t
- origin of replication (ori), 922f
- PDH complex of, 577f
- phospholipid synthesis in, 766f
- plasmid vectors, 306, 306f, 307f
- polar head groups of phospholipids, 769f
- promoters, 1056f
- promoters of, 963–964, 966f, 969t, 1055–1056, 1055f
- protein folding in, 133
- protein synthesis in, 1016t
- protein targeting in, 1045–1046
- recombinant protein expression in, 310, 310f
- ribonucleotide reductase in, 830–832, 830f, 831f, 832f
- ribosomes of, 1015
- RNA polymerase of, 961, 962f
- rRNA processing in, 983–984, 983f
- signaling in, 447f
- SOS response in, 1068–1070, 1070f
- sRNA regulatory actions in, 1071–1073, 1071f, 1072f
- structure of, 5–6, 5f
- terminal sequences in, 967, 967f
- topoisomerases of, 895, 895f
- transcription in, 961–962, 962f
- tryptophan regulation in, 1067–1068, 1067f, 1069f
ESI MS. See electrospray ionization mass spectrometry
essential amino acids, 638, 805
essential fatty acids, 754
estradiol, as cholesterol derivative, 356f
estrogen, 786
- synthesis of, 785–787, 788f
ETF. See electron-transferring flavoprotein
ETF:ubiquinone oxidoreductase, 608f, 671
- electron transfer by, 671, 672f
ethane, oxidation of, 490f
ethanol
- from biomass, 730b–731b
- as fuel, 532
- lipid extraction using, 361
- for methanol poisoning, 198
- oxidation of, 490f
- P-450 enzyme metabolism of, 757b
ethanol fermentation, 514, 525, 525f, 530, 530f, 531–532
ethanolamine, 767f
ethene, oxidation of, 490f
ether lipids, 348, 349f
- synthesis of, 768, 771f
ether-linked fatty alcohols, in plasmalogen synthesis, 768, 771f
ethyl ether, lipid extraction using, 361
Etopophos. See etoposide
etoposide (Etopophos), 906b
euchromatin, 904b, 1075
Eukarya, 3, 4f
eukaryotes, 2
- cells of, 6–8, 7f, 8f
- chromosomes of, 887–890, 888t, 889f
  - complexity of, 889–890, 889f, 890t
- DNA recombination in, 944–948, 944f, 945f
- DNA replication in, 927–929, 929f
- evolution of, 34, 35f, 692–693, 693f
- gene regulation in, 1075
  - developmental control via regulatory protein cascades, 1087–1089, 1087f, 1088f, 1089f, 1090f
  - developmental potential of stem cells, 1091f
  - DNA-binding activators and coactivators in basal transcription factor assembly, 1077–1080, 1079f, 1080f
  - forms of RNA-mediated regulation, 1086
  - intercellular and intracellular signals, 1083–1084, 1083f, 1084f, 1084t
  - modular structure of transcription activators, 1081–1083, 1082f
  - phosphorylation of nuclear transcription factors, 1084
  - positive and negative regulation of galactose metabolism genes in yeast, 1081, 1081f, 1082t
  - positive regulation of promoters, 1077, 1078f
  - posttranscriptional gene silencing by RNA interference, 1085–1086, 1086f
  - structure of transcriptionally active chromatin, 1075–1077, 1076t
  - translational repression of mRNAs, 1084–1085, 1085f
- initiation in, 1029–1030, 1031t
- meiosis in, 944–948, 944f, 945f
- protein targeting in, 1041–1042, 1041f, 1042f
- protein-protein interactions in regulatory proteins of, 1064–1065
- ribosomal RNA processing in, 983–984, 984f, 985f
- ribosomes of, 1018, 1018f
- transcription in
  - $5'$ cap of messenger RNAs, 974, 974f
  - RNA polymerase in, 967–968, 967f
  - $3'$ end of messenger RNAs, 980–981, 980f
- transposition in, 953
- transposons of, 953
eukaryotic cells, 6, 7f
- evolution of, 34–35, 35f
eukaryotic microorganisms, signaling in, 447f
evolution
- accelerated, 331f
- beginnings of, 33
- of biomolecules, 30–31, 32f
- of chloroplasts, 34, 35f, 717–718, 718f
- development link to, 1092b–1093b
- divergent, 584
- of eukaryotic cells, 34–35, 35f
- of first cells, 33–34, 35f
- gene regulation role in, 1092, 1092b–1093b
- of GPCRs, 431–432, 431t, 432f
- of human genome
  - comparisons with closest biological relatives, 329–331, 330f
  - history of, 333–335, 334b–335b, 336f
- landmarks in, 33f
- of living organisms, 2
  - amino acid sequence information on, 96–100, 99f, 100f
- of metabolic regulation, 498
- of mitochondria, 34, 35f, 692–693, 693f
- of photosynthesis, 34, 717–718, 718f
- process of, 30, 31f
- protein structural motifs and, 128
- relationships based on, 35
- RNA world in, 31–33, 33f
  - riboswitches as vestige of, 1073
  - RNA-dependent synthesis as clue to, 998–1001, 999f, 1000b, 1001f
- of RTKs, 437
- of rubisco, 720
- of thymine in DNA, 280
- timeline of, 33, 33f
- of transposons, retroviruses, and introns, 990f, 991–993, 991f
evolutionary trees, from amino acid sequences, 100, 100f
excinucleases, 936
excitable cells, electrical signaling in, 442–443, 443f
excited state, 703
exciton, 704
exciton transfer, 704
- in chlorophyll, 705–707, 707f
- in Fe-S reaction center, 711
- in pheophytin-quinone reaction center, 708, 708f
- in photosystem II, 710, 710f
exenatide (Byetta), 879t
exercise, type 2 diabetes mellitus management with, 878–879, 879t
exergonic reactions, 20, 467
exit (E) site, 1028, 1028f
exocrine glands, aquaporins in, 400
exocytosis, 8
exogenous pathway, 780
- of cholesterol transport, 779f, 780
exoglycosidases, carbohydrate analysis using, 258
exons, 327, 889, 889f, 973
- in human genome, 327, 327f
- in RNA processing, 973
- transcription of, 973
exonucleases, 303t, 916
- in mismatch repair, 934, 936f
exoribonuclease, 987
exosome, 987, 987f
exothermic reactions, 467
exportin-5, 986f
expression. See gene expression
expression vectors, 309, 310f
expressome, 1036
extracellular matrix (ECM), 244–246
- glycosaminoglycans in, 244–246, 246f
- proteoglycans in, 247f, 248–251, 248f, 249f, 252f
extracellular signals, 428f
extraction, lipids, 361, 362f
extrinsic pathway, 222
- in blood coagulation, 221f, 222
eye, GPCR signaling in, 429–431, 429f, 430b, 430f
ezetimibe, 785

F

$f_{1}$ ATPase, 677
$f_{1}$ domain
- of ATP synthase, 677
  - ATP stabilization by, 677–678, 678f
- structure and conformations of, 678–680, 679f
F26BP. See fructose 2,6-bisphosphate
Fab fragment, 165, 166f
facilitated diffusion, 386
F-actin, 169, 170f
factor VII, 221f, 222
factor VIIa, 221f, 222
factor VIII, deficiency of, 222
factor VIIIa, 221f, 222
factor IX, 221f, 222
factor IXa, 221f, 222
factor X, 221f, 222
factor Xa, 221f, 222
factor XI, 221f, 222
factor XIIIa, 221, 221f
facultative anaerobes, 3
FAD. See flavin adenine dinucleotide
familial HDL deficiency, 785, 785f
familial hypercholesterolemia (FH), 782, 785
families, protein, 125
Faraday constant, 467t
farnesoid X receptor (FXR), 784
farnesyl pyrophosphate, 774
- in cholesterol synthesis, 774, 775f
farnesylation, posttranslational, 1039f
FAS. See fatty acid synthase
fasting state
- brain fuel during, 863–864, 864t, 865f, 866f
- fuel metabolism in, 863–864, 863f, 863t, 864t, 865f, 866f
- global carbohydrate metabolism during, 568–570, 569f, 570f
fast-twitch muscle, 853, 854
fat cells, triacylglycerols in, 344–345, 344f
fats. See triacylglycerols
fatty acid elongation systems, 753, 754f
fatty acid oxidation, 341, 344–345
- α oxidation, 618, 618f
- β oxidation, 601
  - of odd-number fatty acids, 612–613, 613f, 614b–615b
  - in peroxisomes, 617–618, 617f, 618f
  - of saturated fatty acids, 607–611, 607f, 608f, 611t
  - of unsaturated fatty acids, 611–612, 612f
- defects in, 617–618
- regulation of, 613, 616, 616f
  - transcription factors regulating proteins for lipid catabolism, 616
- stages of, 606–607, 607f
fatty acid synthase (FAS), 745, 746f, 747f
- acetyl and malonyl group transfer to, 747–748, 749f
- cellular location of, 750–751, 751f
- multiple active sites of, 747, 747f
- repeating reactions of, 745–747, 746f, 747f, 748–750, 749f, 750f
- structure of, 745, 746f
fatty acid synthesis
- acetyl group shuttling for, 751–752, 753f
- in chloroplasts, 750–751, 751f
- in cytosol, 750–751, 751f
- desaturation after, 754–755, 755f, 756b–757b
- fatty acid synthase active sites for, 747, 747f
- fatty acid synthase reactions in, 745, 746f, 747, 747f, 748–750, 749f, 750f
- long-chain, 753, 754f
- malonyl-CoA formation for, 744–745, 745f
- overview of, 616f
- palmitate, 747f, 748–750, 750f
- regulation of, 752–753, 753f
- repeating reaction sequence used in, 745–747, 746f, 747f, 748–750, 749f, 750f
fatty acids, 341
- activation of, 603–606, 605f, 606f
- digestion of, 602–603, 602f
- double bonds in, 341–343
- essential, 754
- ether-linked, 349, 349f, 768, 771f
- gluconeogenesis and, 538
- in glycerophospholipids, 346–348
- ketone bodies from, 619–621, 619f, 620f
- in liver, 850–851, 851f
- mobilization of, 603, 604f, 605f
- nomenclature for, 342, 342t, 343
- partial hydrogenation of, 345, 345f
- pyruvate kinase regulation by, 544, 544f
- as storage lipids, 347f
  - as hydrocarbon derivatives, 341–344, 342t, 343f
  - triacylglycerols, 344–345, 344f
  - waxes, 345–346, 346f
- structure and properties of, 342t, 343, 343f
- transport of, 603–606, 605f, 606f
fatty acyl-carnitine, 605
fatty acyl-CoA dehydrogenase, 607f
- genetic defects in, 616–617
fatty acyl-CoA desaturase, 754, 755f
fatty acyl-CoA synthetases, 603
fatty acyl-CoAs, 604
- β-oxidation of, 609f
- formation of, 485, 603–604, 605f
- transport of, 605–606, 606f
- in triacylglycerol and glycerophospholipid synthesis, 760, 761f
favism, 548b
FBPase-1. See fructose 1,6-bisphosphatase
FBPase-2. See fructose 2,6-bisphosphatase
Fc fragment, 165, 166f
FCCP. See carbonylcyanide-p-trifluoromethoxy
FdG. See 2-fluoro-2-deoxyglucose
feedback inhibition, 27
- in amino acid biosynthesis, 814, 816
- in hormonal signaling, 846
- in purine biosynthesis, 826f, 827
- in pyrimidine biosynthesis, 829, 829f
feeding behavior, hormonal regulation of, 846–847, 847t. See also body mass regulation
Fehling’s reaction, 238b–239b
FeMo cofactor, 797f, 800
fermentation, 511, 525, 526, 530
- microbial, 532
- pyruvate, 525
  - ethanol, 514, 525f, 530, 530f, 531–532
  - foods and industrial chemicals produced by, 530–532
  - lactic acid fermentation, 514, 525f, 526, 529b
  - thiamine pyrophosphate in, 530, 531f, 532t
ferredoxin, 708, 708f, 709f, 714f, 800
- cyclic electron flow with, 713
$ferredoxin : {NAD}^{+}$ reductase, 708, 708f, 709f
$ferredoxin : {NADP}^{+}$ oxidoreductase, 714f
$ferredoxin : {NADP}^{+}$ reductase, 712
ferredoxin-thioredoxin reductase, 723f, 725
ferritin, 584b, 585b
ferrochelatase, 817
Fe-S photochemical reaction center, 708f, 711
- in photosystem I, 711, 711f, 712f
FFAs. See free fatty acids
FGF. See fibroblast growth factor
FGFR. See fibroblast growth factor receptor
FH. See familial hypercholesterolemia
fibrin, 221
- in blood coagulation, 220f, 221, 221f
fibrinogen, 221
- in blood coagulation, 220f, 221, 221f
fibroblast growth factor (FGF), heparan sulfate binding by, 249
fibroblast growth factor receptor (FGFR), 438f
fibroin, structure and function of, 120, 121f
fibronectin, 250
fibrous proteins, 116
- structure of, 116, 117t
  - collagen, 118–120, 119b, 119f, 120f
  - α-keratin, 117–118, 117f
  - silk fibroin, 120, 121f
fidelity, in protein synthesis, 1036
fight-or-flight response
- fuel metabolism during, 864–865, 866t
- global carbohydrate metabolism during, 568–570, 569f, 570f
finches, Galápagos, 1092b–1093b
fingerprinting, DNA, 288b–289b
Fire, Andrew, 1085
firefly, light production by, 486b
first law of thermodynamics, 20
- bioenergetics and, 466–467, 467t
first-order reaction, 150, 182
Fischer, Emil, 72, 183
Fischer projection formulas, 232
- Haworth perspective formula conversions of, 235
- for monosaccharides, 232, 232f
fish oil supplements, 343
$5'$ cap, 974
- of eukaryotic mRNAs, 974, 974f
$5'$ end, 267, 267f
$(5')$ AUG initiation codon, protein synthesis initiation by, 1023–1030, 1028f, 1029f, 1030f, 1031t
$5'\to 3'$ exonuclease activity, in DNA polymerases, 920, 920f
fixation
- carbon, 719
- nitrogen, 795–802, 795f, 797f, 800f, 801f
flagella, 5f
- movement of, 169
- rotation of, 693, 693f
flagellin proteins, 1073, 1074f, 1074t
flavin adenine dinucleotide (FAD), 295f, 295s, 495–496, 495f
- in mitochondrial respiratory chain, 660–662
- in PDH complex, 576
flavin mononucleotide (FMN), 495–496, 495f
- in mitochondrial respiratory chain, 660–662, 664t
flavin nucleotides, 495, 495f, 496
flavoproteins, 83t, 495, 495f, 496, 662
- in mitochondrial respiratory chain, 662
Fleming, Alexander, 210–211
flip-flop diffusion, of membrane lipids, 378–379, 378f
flippases, 378, 378f
floppases, 378–379, 378f
fluid mosaic model, 369, 369f
fluorescence, 704
fluorescence recovery after photobleaching (FRAP), 379
- lipid diffusion studies using, 379–380, 379f
fluorescence resonance energy transfer (FRET), 416b
- signaling pathway studies using, 416b–417b
fluorescent probes
- lipid studies using, 379–380, 379f
- protein localization using, 319–320, 319f, 320f
- signaling pathway studies using, 416b–417b
2-fluoro-2-deoxyglucose (FdG), tumor diagnosis using, 528b
l-fluoroalanine, 820
fluorophores, 319f, 320
fluoroquinolones, 906b
fluorouracil, 836, 836f, 837f
flux (J), 498
fMet. See N-formylmethionine
FMN. See flavin mononucleotide
$F_{o}$ domain, 682f
- of ATP synthase, 677
- proton flow through, rotary motion produced by, 680–682, 681f
- structure and conformations of, 678–680, 679f
foam cells, 784f, 785
folate, deficiency of, 643, 833
folding
- of homopolysaccharides, 243–244, 243f, 244f
- of proteins, 128–136, 129f
  - amino acid sequence role in, 130, 130f
  - assisted, 132–133, 132f
  - defects in, 133–135, 133f, 134b–135b
  - as final step of synthesis, 1015, 1016f, 1016t, 1036–1039, 1037f
  - stepwise process of, 131–132, 131f, 132f
- of ribosomes, 1017
Foldit (video game), 138b–139b
folds, 123
- of globular proteins, 122–124, 123f, 124f, 125f
footprinting, 965b
forensic medicine, PCR use in, 286, 288b–289b
forkhead box other (FOXO1), 546f
formaldehyde, oxidation of, 490f
formic acid, oxidation of, 490f
N-formylmethionine (fMet), 1024, 1028–1029
$N^{10} -formyltetrahydrofolate,$ in purine biosynthesis, 825, 825f
Fos, in cell cycle regulation, 448, 449f
454 sequencing, 292f
FOXO1. See forkhead box other
fractionation, 84
- of proteins, 84–85, 84f, 85f
fractions, protein, 84
frameshifting, 1013, 1013f, 1014f, 1015f
Framingham Heart Study, 786b
Franklin, Rosalind, 270
FRAP. See fluorescence recovery after photobleaching
free energy (G), 20
free-energy change ( $Δ G$ ), 20, 22, 24–25
- for active transport against concentration or electrochemical gradient, 391–392
- additive nature of, 471
- of ATP synthesis on surface of ATP synthase, 677–678, 678f
- in biological systems, 466–467
- of electron transfer in mitochondrial respiratory chain, 672
- in enzymatic reactions, 180–181, 180f, 181f, 185, 185f
- equilibrium constant relationship to, 182, 182t, 468–470, 468t, 469t
- of fatty acyl-CoA formation, 485
- of gluconeogenesis and glycolysis, 534, 535t
- hydrolysis
  - ATP, 479–481, 479f, 480t
  - phosphorylated compounds and thioesters, 481–482, 481f, 481t, 482f
- of metabolic enzymes, 502t
- of oxidation-reduction reactions, 491t, 492
- of peptide bond formation, 1036
- of pumping by symport, 399
- reactant and product concentration effects on, 470–471
- of transmembrane passage, 386, 386f
free-energy content (G), 467
- in biological systems, 466–467
- cell sources of, 467
free fatty acids (FFAs), 603
free-radical reactions, 475, 475f
FRET. See fluorescence resonance energy transfer
Freudenberg, Ernst, 56b
frontotemporal dementia, protein misfolding in, 135
fructans, 874
fructokinase, 524
fructose, 229–230, 230s, 233s
- cyclic forms of, 234, 234f
- in feeder pathways for glycolysis, 522f, 524–525
- sweet taste of, 231b
fructose 1,6-bisphosphatase (FBPase-1), 539, 734f
- in Calvin cycle, 721, 723f
- light activation of, 725, 726f
- regulation of
  - by fructose 2,6-bisphosphate, 542, 543f
  - reciprocal, 541–542, 541f, 542f
fructose 1,6-bisphosphate, 516, 537
- in Calvin cycle, 721, 723f
- in gluconeogenesis, conversion to fructose 6-phosphate, 537
- in glycolytic pathway, 512f, 513, 513f, 516, 517f
- light activation of, 727f
- in pentose phosphate pathway, 549–551, 549f
- in sucrose synthesis, 733
fructose 1,6-bisphosphate aldolase, 516
- in glycolytic pathway, 513f, 516, 517f
fructose 1-phosphate aldolase, 524
fructose 2,6-bisphosphatase (FBPase-2), 542, 543f
fructose 2,6-bisphosphate (F26BP), 542, 734
- PFK-1 and FBPase-1 regulation by, 542, 543f
- in sucrose synthesis, 733–734, 734f
- xylulose 5-phosphate and, 543–544
fructose 6-phosphate, 515, 515s
- in Calvin cycle, 720, 723f
- in gluconeogenesis, 539
- in gluconeogenesis, conversion of fructose 1,6-bisphosphate to, 537
- in glycolytic pathway, 512f, 513f, 515f, 516
- in pentose phosphate pathway, 549, 549f, 550f
- in sucrose synthesis, 733, 733f, 736, 736f
fruit flies, developmental regulation in, 1087–1089, 1087f, 1088f, 1089f, 1090f
F-type ATPases, 395, 395f, 677
fucose, 236f, 237
fuel, storage of, in homopolysaccharides, 241–242, 242f
fuel metabolism, hormonal regulation of, 859
- cortisol effects in, 865–866
- diabetes mellitus and, 875–877
- epinephrine effects in, 864–865, 866t
- during fasting and starvation, 863–864, 864t, 865f, 866f
- glucagon effects in, 862–863, 863f, 863t
- insulin effects in, 859–860, 859t, 860f
- pancreatic β cell insulin secretion in, 860–862, 861f, 862f
fumarase, 579f, 587
- mutations in, 595
fumarate, 586, 587f
- in amino acid degradation, 648f
- hydration of, 579f, 587
- as oncometabolite, 595
- succinate oxidation to, 579f, 586
- in urea cycle, 634f–635f, 635, 636
fumarate hydratase, 579f, 587
functional genomics, 36
functional groups, in biomolecules, 10–11, 12f, 13f
fungi, genetic code variations in, 1010b–1011b
β-furanose, 265s
furanoses, 234, 234f
fusion, of membranes, biological processes using, 382–383, 382f, 383f, 384f
fusion proteins, 313, 383
- for immunoprecipitation, 320–321, 321f
- protein localization with, 319–320, 319f, 320f
- for yeast two-hybrid analysis, 321–322, 322f
FXR. See farnesoid X receptor

G

G. See guanine
G. See free-energy content; Gibbs free energy
G protein–coupled receptor kinases (GRKs), 419
G protein–coupled receptors (GPCRs), 411, 411f, 412
- β-adrenergic receptors
  - cAMP as second messenger of, 412–413, 414f, 415f, 418f, 421
  - cross talk in signaling by, 438, 438f
  - desensitization of, 418–419, 419f
  - as drug targets, 412
  - termination of response by, 416–418
- ${Ca}^{2 +}$ as second messenger of, 425, 425t, 427f
  - space and time localization of, 425–428, 427f, 427t
- cAMP as second messenger of
  - for β-adrenergic receptors, 412–413, 414f, 415f, 418f, 421
  - other regulatory molecules using, 416b–417b, 420, 420t, 421f
- defects in, 412
- diacylglycerol and ${IP}_{3}$ as second messengers of, 425, 425t, 427f
- as drug targets, 412
- in olfaction and gustation, 431
- structure of, 432, 432f
- universal features of, 431–432, 431t, 432f
- in vision, 429–431, 429f, 430b, 430f
G proteins
- as biological switches, 413, 414f, 417, 420–425, 432
- defects in, 412, 423–424
- $G_{i},$ 420
- $G_{olf},$ 431
- $G_{q},$ 425
- $G_{s},$ 413, 414f, 415f, 416, 417, 421
- gustducin, 431
- Ras
  - in cancer, 423
  - in INSR signaling, 434–435, 434f
  - oncogenes encoding, 451, 452b–453b, 455
- transducin, 429f, 430–431, 430b, 430f
G tetraplex, 274, 275f
G0 phase, 446, 447f
G1 phase, 446, 447f
G2 phase, 446, 447f
G6PD. See glucose 6-phosphate dehydrogenase
GABA. See β-aminobutyric acid
G-actin, 169, 170f
gag gene, 989, 989f
GAL genes, positive and negative regulation of, 1081, 1081f, 1082t
Gal4p, 1081–1083, 1082f
galactokinase, 523
galactolipids, 349, 349f
galactosamine, 236, 236f
galactose, 232, 232f, 233s
- in feeder pathways for glycolysis, 522f, 523–524, 524f
- yeast metabolism of, regulation of, 1081, 1081f, 1082t
galactosemia, 523–524, 524f
galacturonic acid, 237
Galápagos finches, 1092b–1093b
gangliosides, 253, 350f, 351, 770
- abnormal accumulations of, 353b
- blood group type and, 253, 351, 351f
- synthesis of, 770, 772f
gap genes, 1088
GAPs. See GTPase activator proteins
Garrod, Archibald, 650
gas chromatography (GC), of lipids, 362, 362f
gas constant, 467t
GAS5. See growth arrest specific 5
gases, solubilities of, 47, 47t
gastric bypass surgery, 878–879, 879t
gastric inhibitory polypeptide, 847t
gastrin, 627, 628f
gastrointestinal stromal tumors, 453b
GATC sequence, in mismatch repair, 932, 933f, 934f
gated ion channels, 386, 387f, 401
- electrical signaling by, 442–443, 443f
- $K^{+}$ channels, 402–403
- in neurons, 443–444, 444f
- as signal receptors, 411, 411f
  - electrical signaling by, 442–443, 443f
  - neuronal action potentials produced by, 443–444, 444f
  - neurotransmitters interacting with, 444
  - toxins targeting, 444–445
GC. See gas chromatography
GDGTs. See glycerol dialkyl glycerol tetraethers
GEFs. See guanosine nucleotide-exchange factors
gel electrophoresis. See electrophoresis
gel filtration. See size-exclusion chromatography
gelatin, 118
gene dosage compensation, 907b
gene drives, 325b
gene expression
- cholesterol regulation by, 782f, 783, 783f
- cloned genes
  - bacteria systems used for, 310, 310f
  - insect and insect virus systems used for, 311–312, 311f
  - mammalian cell systems used for, 312
  - vectors for, 309, 310f
  - yeast systems used for, 310–311
- constitutive, 1056
- diet regulation of, 871–872, 871f
- DNA microarrays showing, 322f
- glycolysis and gluconeogenesis regulation by, 545–546, 545t, 546f
- insulin regulation of, 434f, 435
- leptin triggering of, 869
- in metabolic regulation, 498–499, 499f
- regulated, 1055
- regulation of. See gene regulation
- RNA polymerase II in, 967–968
gene library, 316
gene perturbation, 324, 324f, 326f
gene regulation, 1054, 1055f
- in bacteria
  - coordination of r-protein and rRNA synthesis, 1070–1071, 1070f, 1071f
  - genetic recombination, 1073, 1074f, 1074t
  - induction of SOS response, 1068–1070, 1070f
  - positive regulation of lac operon, 1066–1067, 1066f
  - sRNA regulation of mRNAs, 1071–1073, 1072f
  - transcription attenuation of genes for amino acid biosynthetic enzymes, 1067–1068, 1067f, 1069f
- in eukaryotes, 1075
  - developmental control via regulatory protein cascades, 1087–1089, 1087f, 1088f, 1089f, 1090f
  - developmental potential of stem cells, 1091f
  - DNA-binding activators and coactivators in basal transcription factor assembly, 1077–1080, 1079f, 1080f
  - forms of RNA-mediated regulation, 1086
  - intercellular and intracellular signals, 1083–1084, 1083f, 1084f, 1084t
  - modular structure of transcription activators, 1081–1083, 1082f
  - phosphorylation of nuclear transcription factors, 1084
  - positive and negative regulation of galactose metabolism genes in yeast, 1081, 1081f, 1082t
  - positive regulation of promoters, 1077, 1078f
  - posttranscriptional gene silencing by RNA interference, 1085–1086, 1086f
  - structure of transcriptionally active chromatin, 1075–1077, 1076t
  - translational repression of mRNAs, 1084–1085, 1085f
- in evolution, 1092, 1092b–1093b
- in human evolution, 331
- by nuclear hormone receptors, 445, 446f
- principles of
  - DNA-binding domains of regulatory proteins, 1060–1063, 1060f, 1061f, 1062f, 1063f
  - operons, 1058–1060, 1059f
  - promoters, 1055–1056, 1055f
  - protein-protein interaction domains of regulatory proteins, 1063–1065, 1064f
  - transcription initiation regulation, 1056–1057, 1057f, 1058f
gene sharing, 584b
gene silencing, by RNA interference, 1085–1086, 1086f
gene transfer, horizontal, 99
general acid-base catalysis, 187
- chymotrypsin, 205, 205f
- enzymatic, 186–187, 187f
general transcription factors, 968
- DNA-binding activators and coactivators in assembly of, 1077–1080, 1079f, 1080f
genes, 263, 886, 886f
- allocation of, 36
- alternative splicing of, 981–983, 983f
- cloned. See DNA cloning
- coding strand for, 962, 962f
- comparisons of, 317–318, 318f
- CRISPR/Cas inactivation or alteration of, 322–324, 323f
- directed mutagenesis of, 312–313, 312f
- disease-involved, localization of, 331–333, 332f
- duplication, 31f
- eukaryotic, 887–890, 888t, 889f
  - complexity of, 889–890, 889f, 890t
- homeotic, 1088, 1089, 1090f
- homologous, 35
- housekeeping, 36, 1056
- in human genome, 327–329
- immunoglobulin, recombination of, 953–955, 954f, 955f
- inducible, 1054
- isolation of, by DNA cloning, 302
- jumping, 940–941
- maternal, 1087, 1088, 1089f
- mitochondrial, 692, 692t, 693f
  - mutations in, 693–696, 694f, 695f, 696f
  - origin of, 692–693, 693f
- mutation, 31f
- naming conventions of, 914–915
- ORFs pointing to, 1009
- PCR amplification of, 283–286, 285f, 288b–289b
- poly(A) site choice and, 982, 983f
- promoters and, 963
- repressible, 1054
- RNA as first, 31–33, 33f
- segmentation, 1087, 1088, 1090f
genes, bacterial, naming conventions of, 914–915
genetic code
- cracking of, 1006–1007, 1007f
  - artificial mRNA templates used for, 1007–1009, 1007f, 1008t, 1009f, 1010b–1011b, 1012t
- degeneracy of, 1009t
- expansion of, 1025b–1027b
- mutation resistance of, 1012–1013
- natural variations in, 1010b–1011b
- reading of, translational frameshifting and RNA editing in, 1013, 1013f, 1014f, 1015f
- second, 1022–1023
- wobble in, 1010–1012, 1012f, 1012t
genetic continuity, 28
genetic disease
- abnormal accumulations of membrane lipids, 353b
- ADA deficiency, 834–835
- ATP-gated $K^{+}$ channel mutations, 862
- citric acid cycle mutations, 594–595, 595f
- defective ABC transporters, 396, 397b–398b
- defective ion channels, 397b–398b
- defective water transport, 400
- defects of amino acid metabolism, 646, 646t, 648–653, 649f, 653b, 654f
- fatty acyl-CoA dehydrogenase defects, 616–617
- G6PD deficiency, 548b
- glycogen storage diseases, 561b–562b
- hemophilias, 222–223, 223f
- Lesch-Nyhan syndrome, 835
- localization of genes involved in, 331–333, 332f
- mitochondrial gene mutations, 693–696, 694f, 695f, 696f
- pernicious anemia, 615b
- peroxisome defects, 617
- porphyrias, 817, 819b
- protein misfolding, 133–135, 133f
- Refsum disease, 618
- sickle cell anemia, 162–164, 163f
- transketolase defects, 551
- ubiquitination defects, 1049
- urea cycle defects, 638–639, 638t, 639f
genetic engineering, 302. See also DNA cloning; recombinant DNA
genetic information, 884–885
- DNA storage of, 270–272, 271f, 272f
genetic mutation, evolution through, 30, 31f
genetic recombination. See also DNA recombination
- functions of, 941–943
- gene regulation by, 1073, 1074f, 1074t
- homologous, 940–948
- site-specific, 940, 950–951, 951f, 952f
genetic screening, 324–325, 324f, 326f
genome annotation, 317
genomes, 2, 13, 35–36, 301
- comparisons of. See comparative genomics
- completed sequences of, 35, 326–327, 327f
- human. See human genome
- mitochondrial, 301, 692, 692t, 693f
genomics, 13, 301
- comparative, 36, 317–318, 318f
  - closest biological relatives of humans, 329–331, 330f
  - genes involved in disease, 331–333, 332f
  - human history learned from, 333–335, 334b–335b, 336f
- completed sequences, 35, 326–327, 327f
- functional, 36
- history of, 326–327, 327f
- human genome sequencing, 326–327, 327f
  - comparisons with closest biological relatives, 329–331, 330f
  - evolutionary history learned from, 333–335, 334b–335b, 336f
  - history of, 326–327, 327f
  - localization of disease genes in, 331–333, 332f
  - types of sequences seen in, 327–329, 327f
genotyping, DNA, 288b–289b
geometric isomers, 15, 15f
geraniol, 356
geranyl pyrophosphate, 774
- in cholesterol synthesis, 774, 775f
GFP. See green fluorescent protein
GFR. See glomerular filtration rate
ghrelin, 846, 872
- blood concentrations of relative to meal times, 873f
- body mass regulation by, 872–874, 874f
- feeding behavior regulation by, 847t
$G_{i} .$ See inhibitory G protein
Gibbs, J. Willard, 21, 24, 467
Gibbs free energy (G), 24, 467. See also free energy (G)
- in biological systems, 467
- cell sources of, 467
Gilbert, Walter, 286
GIP. See glucose-dependent insulinotropic polypeptide
Gla residues. See β-carboxyglutamate residues
Gleevec. See imatinib mesylate
glial cell tumors, 595
gliflozins, ${Na}^{+} -glucose$ symporter inhibition by, 399
glimepiride (Amaryl), 879t
gliomas, 595
glipizide (Glucotrol), 879t
global warming, 730b–731b
globin fold, 149
globins, 149. See also hemoglobin; myoglobin
- family of, 149
- heme in, 148–149, 148f
- structure of, binding effects of, 152–153, 153f
globosides, 350f, 351
globular proteins, 116–117
- structure of, 120–121, 121f
  - classification based on, 125–126, 127f
  - motifs and domains, 123–124, 123f, 124f, 125f
  - myoglobin, 121–123, 122f, 137
glomerular filtration rate (GFR), 857b
GLP-1. See glucagon-like peptide-1
glucagon, 542,, 862
- cAMP signaling by, 420
- in cholesterol regulation, 782, 782f
- feeding behavior regulation by, 847t
- fuel metabolism regulation by, 862–863, 863f, 863t
- in global regulation of carbohydrate metabolism, 568–570, 569f, 570f
- glycogen phosphorylase regulation by, 565f, 566, 566f
- pancreatic secretion of, 860, 861f
- triacylglycerol mobilization by, 603, 604f
- triacylglycerol synthesis regulation by, 762
glucagon-like peptide-1 (GLP-1), 847t
- modulators of, 879t
glucocorticoids, 785
- phosphoenolpyruvate carboxykinase regulation by, 763, 763f
- synthesis of, 785–787, 788f
glucogenic amino acids, 538, 538t, 640
glucokinase. See hexokinase IV
gluconeogenesis, 510–511, 510f, 533, 533f, 850
- bioenergetics of, 534, 535t, 537–538, 537t
- from citric acid cycle intermediates and amino acids, 538, 538t
- conversion of fructose 1,6-bisphosphate to fructose 6-phosphate, 537
- conversion of glucose 6-phosphate to glucose, 537
- conversion of pyruvate to phosphoenolpyruvate, 534–537, 535f, 536f
- energy expensiveness of, 537–538, 537t
- fatty acids and, 538
- in germinating seeds, 735–736, 736f
- glycolysis steps shared with, 534, 534f
- precursors of, 533, 534f
- regulation of, 539
  - ATP in allosteric inhibition of pyruvate kinase, 544, 544f
  - conversion of pyruvate to phosphoenolpyruvate, 544–545, 544f
  - fructose 2,6-bisphosphate in allosteric regulation of PFK-1 and FBPase-1, 542, 543f
  - glycolysis coordination with, 539
  - hexokinase isozyme responses to glucose 6-phosphate, 539–541, 539f, 540b
  - reciprocal regulation of phosphofructokinase-1 and fructose 1,6-bisphosphatase, 541–542, 541f, 542f
  - transcriptional regulation of number of enzyme molecules, 545–546, 545t, 546f
  - xylulose 5-phosphate as key regulator in, 543–544
gluconic acid, 237
Glucophage. See metformin
glucosamine, 236, 236f
- in bacterial and algal cell walls, 244
glucosaminoglycan, 246f
glucose, 229–230, 230s, 233s, 514s
- amino acid conversion to, 640, 640f
- anaerobic degradation of. See fermentation
- biological derivatives of, 236–237, 236f
- blood concentrations of relative to meal times, 873f
- blood levels of. See blood glucose
- brain requirements for, 533, 557, 855–856, 855f
- in cellulose, 243, 243f, 736–738, 737f
- conversion of glucose 6-phosphate to, 537
- cyclic forms of, 234, 234f, 236f
- epimers of, 232, 232f
- fatty acid conversion to, 538
- global regulation of, 568–570, 569f, 570f
- in glycogen, 242, 242f
- glycogen phosphorylase as sensor of, 566, 566f
- hexokinase reaction with, 209–210, 210f
- insulin regulation of, 435–437, 436f
- lac operon regulation by, 1066–1067, 1066f
- liver metabolism of, 849–850, 850f
- major pathways of, 510–511, 510f
- ${Na}^{+} -glucose$ symporter transport of, 398–399, 399f
- phosphorylation of, as first step in glycolytic pathway, 513f, 514–515
- as reducing sugar, 237, 238b–239b
- in regulation of fatty acid oxidation, 613, 616f
- in starch, 242, 242f, 733
- sweet taste of, 231b
- synthesis of. See gluconeogenesis
glucose 1-phosphate
- fates of, 559–560, 559f
- galactose conversion to, 524f
- glycogen degradation into, 558f, 559f
- in starch synthesis, 733
glucose 6-phosphatase, 537
- in glycogen breakdown into glucose, 559f, 560f
glucose 6-phosphate, 236f, 237, 496, 514, 514s, 515s
- in gluconeogenesis, conversion to glucose, 537
- glucose 1-phosphate conversion to, 559–560, 559f
- in glycolysis, 512f, 513f, 514–515, 515f
  - partitioning between pentose phosphate pathway and, 551, 551f
- hexokinase isozyme responses to, 539–541, 539f, 540b
- hydrolysis of, 560f
- liver metabolism of, 849–850, 849f
- in pentose phosphate pathway, 546, 547f, 549–551, 549f, 550f
  - partitioning between glycolysis and, 551, 551f
- in sucrose synthesis, 735f
glucose 6-phosphate dehydrogenase (G6PD), 547–548
- deficiency of, 548b
- light regulation of, 726
- in pentose phosphate pathway, 547, 547f
glucose oxidation
- ATP yielded from, 589t, 686–687, 686t
- electron carriers for, 492
- by glycolysis. See glycolysis
- by pentose phosphate pathway. See pentose phosphate pathway
glucose tolerance test, 390b
glucose transporter 1 (GLUT1)
- defects in, 389
- passive transport mediated by, 387–389, 387f, 388f, 389f, 389t
- in tumors, 527b–528b
glucose transporter 2 (GLUT2), 389, 389t, 399f, 539
glucose transporter 3 (GLUT3), in tumors, 527b–528b
glucose transporter 4 (GLUT4), 389, 389t, 390b, 570
- insulin regulation of, 435–437, 436f
glucose uptake
- in diabetes mellitus, 875–877
- insulin stimulation of, 859–860, 859t, 860f
- in tumors, 527b–528b
- in type 1 diabetes mellitus, 390b
- by various tissues, 389, 390b
glucose-alanine cycle, 632, 632f
glucose-dependent insulinotropic polypeptide (GIP), 847t
glucose-tolerance test, 877
Glucotrol. See glipizide
glucuronic acid, 245
GLUT1. See glucose transporter 1
GLUT2. See glucose transporter 2
GLUT3. See glucose transporter 3
GLUT4. See glucose transporter 4
glutamate, 74s, 76, 650, 802, 806
- ammonia assimilation into, 802–803
- in citric acid cycle, 590
- in general acid-base catalysis, 187f
- metabolism of, 626–627, 627f
  - carbon skeleton degradation, 640f, 650, 651f
  - formation by transamination reactions, 628–630, 629f, 630f
  - release of amino group as ammonia, 630–631, 632f
- as neurotransmitter, 444
- neurotransmitter synthesis from, 821–822, 823f
- properties and conventions associated with, 73t
- titration curve of, 80, 80f
l-glutamate dehydrogenase, 631, 631f, 802
- oxidative deamination of glutamate by, 630–631, 632f
glutamate β-methyl ester, 77s
glutamate synthase, 802
glutamate-oxaloacetate transaminase (GOT), 637
- tissue-damage assays using, 637b
glutamate-pyruvate transaminase (GPT), 632f
- tissue-damage assays using, 637b
glutaminase, 631, 632f
glutamine, 74s, 76, 650, 802, 806
- ammonia assimilation into, 802–803
- gluconeogenesis from, 538, 538t
- histidine biosynthesis from, 814, 815f
- metabolism of, 626–627, 627f
  - ammonia transport in bloodstream, 631–632, 632f
  - carbon skeleton degradation, 640f, 650, 651f
- properties and conventions associated with, 73t
- in purine biosynthesis, 825, 826f
glutamine amidotransferases, 804, 804f
- inhibition of, 836
glutamine synthetase, 82t, 223, 631,, 632f, 802
- as primary regulatory point in nitrogen metabolism, 803–804, 803f, 804f
glutamine-rich domain, 1082, 1082f
glutaredoxin, 830
- in deoxyribonucleotide synthesis, 830, 830f
glutathione (GSH), 819
- biosynthesis of, 819–820, 821f
glutathione peroxidase, 674, 820
glutathione-S-transferase (GST) tag, 313, 314f
glyburide (Micronase), 879t
glycans, 241. See also polysaccharides
glycation, of hemoglobin, 238b–239b
glyceraldehyde, 230, 230s, 233s
- stereoisomerism of, 232, 232f
glyceraldehyde 3-phosphate, 516
- in Calvin cycle, 719–722, 720f, 723f, 724f, 726f
- in glycolytic pathway, 512f, 513, 513f, 516, 517f, 518f, 519f
- in pentose phosphate pathway, 549, 549f, 550f
- in sucrose synthesis, 733
- 3-phosphoglycerate conversion to, 720f, 721–722
glyceraldehyde 3-phosphate dehydrogenase, 518, 721, 726f
- in glycolytic pathway, 513f, 518, 525f
- light activation of, 725, 727f
glycerol
- glucose synthesis from, 533, 534f, 538
- in glycerophospholipids, 346–347, 347f
- in triacylglycerol and glycerophospholipid synthesis, 760, 761f
- triacylglycerols as fatty acid esters of, 344, 344f
glycerol 3-phosphate
- adipose tissue generation of, 762–763, 762f, 763f
- glycerophospholipids as derivatives of, 347, 347f
- in sucrose synthesis, 735f, 736
- in triacylglycerol and glycerophospholipid synthesis, 760, 761f
glycerol 3-phosphate dehydrogenase, 671, 760, 761f
- electron transfer by, 671, 672f
- in glyceroneogenesis, 762f, 763
glycerol 3-phosphate shuttle, 684, 686f
glycerol kinase, 603, 605f, 760, 761f
glyceroneogenesis, 538, 762
- glycerol 3-phosphate from, 762f, 763, 763f
- increasing to treat type 2 diabetes, 763–764
- regulation of, 763, 763f
- thiazolidinedione effects on, 763–764
glycerophospholipids, 346
- as membrane lipids
  - as derivatives of phosphatidic acid, 346–348, 347f, 348f
  - ether-linked fatty acids in, 349, 349f
  - lysosome degradation of, 352, 353b
- synthesis of
  - attachment of phospholipid head groups, 764–765, 764f
  - CDP-diacylglycerol in, 765–767, 766f, 768f
  - eukaryotic pathways to phosphatidylserine, phosphatidylethanolamine, and phosphatidylcholine, 767–768
  - plasmalogen, 768–770, 771f
  - precursors for, 760, 761f
  - transport to cellular membranes after, 770
glycine, 74, 74s, 644, 808
- biosynthesis of, 806–809, 807f
- catabolism of, 640f, 644–647, 644f, 645f, 646t
- in glycolate pathway, 725f, 728, 728f
- as neurotransmitter, 444
- porphyrin biosynthesis from, 817, 817f, 819b
- properties and conventions associated with, 73t
- in purine biosynthesis, 825, 825f
- receptors for, 444
- titration curve of, 78–79, 78f, 79f
glycine cleavage enzyme, 644, 644f, 645f, 808
glycine decarboxylase complex, 728, 728f, 729
glycine synthase, 808
glycobiology, 254. See also sugar code
glycocalyx, 247
glycoconjugates, 229, 248
- glycolipids, 253, 253f
- glycoproteins, 248
  - posttranslational modifications creating, 1038
  - in protein targeting, 1042–1045, 1043f, 1044f
  - structure of, 247f, 252f
- information carried by, 247, 254
  - lectin reading of, 254–256, 255f, 256f
  - lectin-carbohydrate interactions, 256–257, 257f, 258f
- lipopolysaccharides, 253, 253f
- proteoglycans
  - human diseases involving, 251b
  - structure and function of, 247–253, 247f, 248f, 249f, 252f
  - structure of, 247–248, 247f
glycogen, 229, 242
- breakdown of. See glycogenolysis
- in feeder pathways for glycolysis
  - hydrolysis of, 522f, 523–525
  - phosphorolysis of, 522, 522f
- folding of, 243–244, 244f
- fuel storage in, 242, 242f
- global regulation of, 568–570, 569f, 570f
- granules of, 557–558, 557f
- insulin regulation of, 435–437, 436f
- in liver, 849, 850f
- in muscle, 852–855, 854f, 855f, 856b–857b
- structure and function of, 556–558
- structures and roles of, 247t
- synthesis of. See glycogenesis
glycogen phosphorylase, 477b, 522, 522, 522f
- allosteric and hormonal regulation of, 565–567, 565f, 566f
- glycogen breakdown by, 558–559, 558f, 559f
- regulation of, 217–218, 218f, 223
glycogen phosphorylase a, 565, 565f, 566, 566f
glycogen phosphorylase b, 565, 565f, 566, 566f
glycogen storage diseases, 561b–562b
glycogen synthase, 562, 563f
- phosphorylation and dephosphorylation of, 565–567, 567f, 568f
- phosphorylation of, 218
glycogen synthase a, 567, 567f, 568f
glycogen synthase b, 567, 567f, 568, 568f
glycogen synthase kinase 3 (GSK3), 435, 436f, 567
- autoinhibition of, 440, 440f
- glycogen synthase regulation by, 567f, 568, 568f
- insulin actions mediated by, 567–568, 568f
glycogen-branching enzyme, 563, 563f
glycogenesis
- in bacteria, 733
- glycogenin in, 563–565, 564f
- regulation of
  - allosteric and hormonal regulation of glycogen phosphorylase, 565–567, 565f, 566f
  - allosteric and hormonal signals in global carbohydrate metabolism, 568–570, 569f, 570f
  - GSK3 mediation of insulin, 567–568, 568f
  - phosphorylation and dephosphorylation of glycogen synthase, 565–567, 567f, 568f
  - PP1 role in, 568, 569f
- UDP-glucose in, 560–563, 563f
glycogenin, 563–565, 563f, 564f
glycogenolysis
- glucose 1-phosphate fates after, 559–560, 559f
- glycogen phosphorylase catalysis of, 558–559, 558f, 559f
- regulation of
  - allosteric and hormonal regulation of glycogen phosphorylase, 565–567, 565f, 566f
  - allosteric and hormonal signals in global carbohydrate metabolism, 568–570, 569f, 570f
  - GSK3 mediation of insulin, 567–568, 568f
  - phosphorylation and dephosphorylation of glycogen synthase, 565–567, 567f, 568f
  - PP1 role in, 568, 569f
glycogen-targeting proteins, 568, 569f
glycolate pathway in, 727
glycolipids, 248, 253, 253f, 346, 347f, 349
glycolysis, 510–511, 510f
- aerobic, 525
- bioenergetics of, 534, 535t, 537, 537t
- coupling of ATP and NADH formation to, 513–514
- feeder pathways for
  - glycogen and starch, 522, 522f
  - monosaccharides, 522f, 523–525, 524f
  - polysaccharides and disaccharides, 522f, 523–525
- gluconeogenesis steps shared with, 534, 534f
- glucose 1-phosphate entry into, 559–560, 559f
- glucose 6-phosphate partitioning between pentose phosphate pathway and, 551, 551f
- glycerol entry into, 605f
- in liver, 849, 850f
- net ATP gain in, 521
- payoff phase of, 512f, 513, 518–521
  - conversion of 3-phosphoglycerate to 2-phosphoglycerate, 513f, 520, 520f
  - dehydration of 2-phosphoglycerate to phosphoenolpyruvate, 513f, 520–521
  - oxidation of glyceraldehyde 3-phosphate to 1,3-bisphosphoglycerate, 513f, 518, 525f
  - phosphoryl transfer from 1,3-bisphosphoglycerate to ADP, 513f, 518–520
  - transfer of phosphoryl group from phosphoenol pyruvate to ADP, 513f, 521
- phosphorylated intermediates in, 514
- preparatory phase of, 511–513, 512f
  - cleavage of fructose 1,6-bisphosphate, 513f, 516, 517f
  - conversion of glucose 6-phosphate to fructose 6-phosphate, 513f, 515–516, 515f
  - interconversion of triose phosphates, 513f, 516–518, 518f
  - phosphorylation of fructose 6-phosphate to fructose 1,6-bisphosphate, 513f, 516
  - phosphorylation of glucose, 513f, 514–515
- pyruvate formed by, 510–511, 510f, 512f
  - energy remaining in, 514
  - fates of, 525f
  - by phosphoryl group transfer from phosphoenolpyruvate to ADP, 513f, 514–515
- regulation of, 527b–528b, 539
  - ATP in allosteric inhibition of pyruvate kinase, 544, 544f
  - conversion of pyruvate to phosphoenolpyruvate, 544–545, 544f
  - fructose 2,6-bisphosphate in allosteric regulation of PFK-1 and FBPase-1, 542, 543f
  - gluconeogenesis coordination with, 539
  - hexokinase isozyme responses to glucose 6-phosphate, 539–541, 539f, 540b
  - reciprocal regulation of PFK-1 and FBPase-1, 541–542, 541f, 542f
  - transcriptional regulation of number of enzyme molecules, 545–546, 545t, 546f
  - xylulose 5-phosphate as key regulator in, 543–544
- in tumors, 526, 527b–528b
glycolysis and gluconeogenesis coordination, 27
glycome, 13

glycomics, 252

glycophorin, 372

hydropathy plots, 375f

membrane anchoring of, 380, 380f

in plasma membrane, 372f, 374, 375f

glycoproteins, 83, 83t, 248

posttranslational modifications creating, 1038

in protein targeting, 1042–1045, 1043f, 1044f

structure of, 247f, 251–253, 252f

glycosaminoglycans, 245

in ECM, 244–246, 246f

human diseases involving, 251b

in proteoglycans, 247–253, 247f, 248f, 249f, 252f

glycosidases, carbohydrate analysis using, 258

glycosides, 240f

glycosidic bond

in disaccharides, 239–240, 240f, 240t

in homopolysaccharides, 243, 244f

glycosidic bonds, 229, 237f

glycosphingolipids, 248, 350

as membrane lipids, 350, 351f

rafts of, 380–382, 380f, 381f

structure of, 247f

glycosyl (4→6) transferase, 563

glycosyl groups, transfer of, 475–476

glycosyl phosphatidylinositol (GPI), 376f

as membrane protein anchor, 375–377, 376f. See also GPI-anchored proteins

glycosylation, 252–253, 252f

in protein targeting, 1042–1045, 1043f, 1044f

glyoxylate, 646s, 735

glyoxylate cycle, 590, 735

in plants, 735–736, 736f

glyoxysomes, 7f, 617f, 735

glypicans, 248, 248f

GMP. See guanylate

Goldberger, Joseph, 494

golden rice, 358, 358f

Goldstein, Joseph, 782, 786b

$G_{olf},$ 431

Golgi apparatus, membrane modification in, 369–371, 370f, 371f, 770

Golgi complexes, 6, 7f

GOT. See glutamate-oxaloacetate transaminase

gout, excess uric acid causing, 835–836

GPCRs. See G protein–coupled receptors

GPI. See glycosyl phosphatidylinositol

GPI-anchored proteins, 376

in cholesterol-sphingolipid rafts, 380–382

GPT. See glutamate-pyruvate transaminase

$G_{q},$ 425

Gram, Hans Christian, 6

gram-negative bacteria, 5f, 6

gram-positive bacteria, 5f, 6

granal thylakoids, 701

Grb2. See growth factor receptor-bound protein 2

${green}^{-}$ dichromats, 430b, 430b

green fluorescent protein (GFP), 319, 416b

protein localization using, 319–320, 319f, 320f

signaling pathway studies using, 416b–417b

green sulfur bacteria, 708

Fe-S, 708f, 709

reaction center of, 708, 708f

green-anomalous trichromats, 430b

Greenberg, G. Robert, 825

greenhouse effect, 730b–731b

Greider, Carol, 993

grizzly bear, fatty acid oxidation in, 610b

GRK2. See β-adrenergic receptor kinase

GRKs. See G protein–coupled receptor kinases

gRNAs. See guide RNAs

GroEL/GroES system, 133, 141f

ground state, 180, 704

of chemical reactions, 180, 180f

ground substance. See extracellular matrix

group transfer reactions, 475–476, 476f

energy provided by, 482–484

phosphoryl group. See phosphoryl group transfers

growth, mTORC1 pathway regulation of, 871, 871f

growth arrest specific 5 (GAS5), 1084

growth factor receptor-bound protein 2 (Grb2), 434, 434f, 435

growth factor receptors

oncogenes encoding, 451, 452b–453b

RTK signaling by, 437, 438f

growth factors, 448

cell cycle regulation by, 448, 449f

insulin actions as, 434f, 435

growth retardation, vitamin A deficiency causing, 357–358

$G_{s} .$ See stimulatory G protein

GSH. See glutathione

GSK3. See glycogen synthase kinase 3

GST tag. See glutathione-S-transferase tag

GTP. See guanosine triphosphate

GTPase, of G proteins, 413, 415f, 417, 421–425, 424f, 431, 432

GTPase activator proteins (GAPs), 417, 422, 432

in β-adrenergic signaling, 417

guanine (G), 264, 264s, 265t

base pairing of, 269f

biosynthesis of, 825–827, 826f, 827f

deamination of, 280, 281f

degradation of, 833–836, 834f, 835f

methylation of, 283

guanosine, 266s

guanosine $3', 5' -cyclic monophosphate$ (cyclic GMP, cGMP), 422b, 422s

in guanylyl cyclase signaling, 422b–423b

as regulatory molecule, 296, 296f

guanosine $5' -monophosphate$ (GMP), 422s

guanosine nucleotide-binding protein, 412

guanosine nucleotide-exchange factors (GEFs), 413, 422

guanosine triphosphate (GTP)

as chemical energy carrier, 294

in eukaryotic mRNAs, 974, 974f

in initiation, 1028, 1028f

in succinyl-CoA synthetase reaction, 579f, 584–586, 586f

guanylate (GMP), 265t, 486

biosynthesis of, 825–827, 826f, 827f

degradation of, 833–836, 834f, 835f

guanylin, 423b

guanylyl cyclases, receptor, 422b–423b

guide RNAs (gRNAs), 323, 1013

Guillain-Barré syndrome, gangliosides in, 351

gulose, 233s

gustation, GPCR signaling in, 431

gustducin, 431

gut microbes, body mass regulation by, 874–875, 875f

György, Paul, 56b

H

H. See enthalpy

$H^{+}$ ATPase, structure of, 392–393, 393f

H2AX, 904b

H2AZ, 904b

$H_{4}$ folate. See tetrahydrofolate

HA protein. See hemagglutinin protein

HACs. See human artificial chromosomes

hair, structure of, 117–118, 117f

hairpins, 273

in DNA, 273–274, 274f

in replication fork, 916, 916f

in RNA, 276–277, 276f

in transcription termination, 967, 967f

Haldane, J. B. S., 56b, 183, 190

half-life, of proteins, 499t, 1049, 1049t

half-reactions, 489

standard reduction potentials of, 491t

hammerhead ribozyme, 996, 998f

Hanson, Richard, 762

haplotypes, 328

human, 329f, 333

haptens, 165

HAR1F locus, 331f

Harden, Arthur, 514

Hartley, B. S., 204

HATs. See histone acetyltransferases

Haworth perspective formulas, 234f, 235

Fischer projection formula conversion to, 235

Hb. See hemoglobin

HbA1c measurements, 238b–239b

HbS. See hemoglobin s

HCR. See hemin-controlled repressor

HDACs. See histone deacetylases

HDL. See high-density lipoprotein

heart

muscle tissue of. See cardiac muscle

NO effects on, 423b

plasmalogens in, 348

heart attack

LDH isozymes as markers of, 540b

liver enzyme assays for, 637b

heat

brown adipose tissue production of, 689–890, 690f, 851f, 852, 853f

mitochondrial production of, 689, 690f

plant production of, 685b

heat of vaporization, of water, 44–45

heat production, shivering, 855

heat shock genes, promoters of, 964, 1056f

heat shock RNA 1 (HSR1), 1086

heavy chains

immunoglobulin, 165–166, 166f, 167f

recombination in, 953–955, 954f

myosin, 169, 169f

helicases, 921

in DNA replication, 921–922, 923f, 923t

in mismatch repair, 934, 936f

helix-turn-helix, 1061, 1062, 1062f

helper T $(T_{H})$ cells, 165

hemagglutinin (HA) protein, 255

heme, 122, 148

biosynthesis of, 818f

of Complex II, 667–668, 667f

in cytochrome P-450 enzymes, 690

in cytochromes, 663f, 664

degradation of, 817–819, 820f

glycine in biosynthesis of, 817–819, 817f, 819b

oxygen binding to, 148–149, 148f, 149f

protein structure influences on, 152–153, 153f

structure of, 148–149, 148f, 149f

heme oxygenase (HO), 817, 819, 820f

hemiacetals, 234

formation of, 234, 234f

hemiketals, 234

formation of, 234, 234f

hemin-controlled repressor (HCR), 1085

hemocytoblasts, 153

hemoglobin (Hb), 82, 82t, 148

carbon monoxide binding by, 158b–159b

${CO}_{2}$ transport by, 160–161, 160f

function of, 149

heme in, 148–149, 148f

hydrogen ion transport by, 160–161, 160f

oxygen binding by

conformational changes upon, 153, 155f, 156f, 157, 160f

cooperative nature of, 155–156, 156f, 160f

Hill plot for, 157, 160f

mechanistic models of, 158–160, 160f

pH effects on, 160–161, 161f

quantitative description of, 156–157, 160f

regulation of, 161–162, 162f

oxygen transport by, 153

in sickle cell anemia, 162–164, 163f

structure of, 127–128, 128f

subunits, 153–155, 153f, 154f

water binding in, 50–51, 50f, 51f

hemoglobin glycation, 239b

hemoglobin S (HbS), 162–164, 162f, 163f

hemophilias, 222–223, 223f

hemoproteins, 83t

Henderson-Hasselbalch equation, 60

Henri, Victor, 189

Henseleit, Kurt, 633

heparan sulfate, 246, 246f, 248, 248f, 249f

thrombin binding and, 249–250, 249f

heparins, 222, 246, 246f

hepatocytes, 849

heptahelical receptors, 413

heptoses, 231

HER2/neu receptor, 452b–453b

Herceptin. See trastuzumab

hereditary paraganglioma, 667–668

herpes simplex virus, DNA polymerase of, 929

Hershey, Alfred D., 270

heterochromatin, 903, 1075

heterogeneous ribonuclear proteins (hnRNPs), 981

heterolytic cleavage, 472, 472f

heteroplasmy, 694

in mitochondrial inheritance, 694, 694f

heteropolysaccharides, 241, 241f

in bacterial and algal cell walls, 244

glycosaminoglycans in ECM, 244–246, 246f

heterotrimeric G proteins, 413

heterotrophs, 4f, 5, 461

carbon, oxygen, and water cycling by, 461–462, 462f

nitrogen cycling by, 462, 462f

heterotropic allosteric enzymes, 214–215, 216f

heterotropic binding, 157

hexacosanoic acid, 617

hexokinase, 29f, 31f, 82t, 515

classification of, 179

in glycolytic pathway, 513f, 515

inhibitors of, for cancer treatment, 527b–528b

mechanism of, 209–210, 210f

in metabolic regulation and control, 503

regulation of, isozyme responses to glucose 6-phosphate, 539–541, 539f, 540b

hexokinase I, 539, 539f

hexokinase II, 539, 539f

hexokinase isozyme responses to glucose 6-phosphate, 539–541

hexokinase IV, 539–540, 539f, 541f, 569, 849

hexose monophosphate pathway, 546. See also pentose phosphate pathway

hexose phosphates, movement of, 738–739, 738f

hexoses, 230f, 231

asymmetric centers of, 232, 232f

in living organisms, 236–237, 236f

hibernation

fatty acid oxidation during, 610b

mitochondrial heat production during, 690

HIF-1. See hypoxia-inducible transcription factor

high blood glucose, insulin counteractions of, 859–860, 859t, 860f

high mobility group (HMG), 1079, 1080f

high-affinity nerve growth factor receptor (TrkA), 438f

high-density lipoprotein (HDL), 603, 780

in atherosclerosis, 784–785, 784f, 786b–787b

cholesterol transport as, 778f, 778t, 779f, 779t, 780–781, 780f, 785, 785f

trans fatty acid effects on, 345

high-energy phosphate compounds, 483f, 484

highly repetitive sequences, 890

high-performance liquid chromatography (HPLC), 86,

high-throughput genetic screening, 324f, 326f

Hill, Archibald, 157

Hill, Robert, 702

Hill coefficient $(n_{H}),$ 157

in metabolic regulation, 500, 500t

Hill equation, 157

Hill plot, 157

for oxygen binding to myoglobin and hemoglobin, 157, 160f

Hill reaction, 702

Hill reagent, 702–703

Hin recombinase, 1073, 1074f, 1074t

HIRA, 904b

his operon, 1068

histamine, 822, 823f

histidine, 74s, 76, 650, 812

biosynthesis of, 812–814, 815f

as buffer, 61, 61f

catabolism of, 640f, 650, 651f

in general acid-base catalysis, 187f

histamine synthesis from, 822, 823f

properties and conventions associated with, 73t

titration curve of, 80, 80f

histone acetyltransferases (HATs), 1076, 1080

histone chaperones, 901, 904b

histone deacetylases (HDACs), 1077

histone demethylases, 2-hydroxyglutarate inhibition of, 595, 595f

histone exchange factors, 902

histone modifications, 899, 904b–905b, 1075–1077, 1076t

histones, 899

in nucleosomes, 899–900, 899f, 900f, 901f

variants, 904b–905b, 1075–1077, 1076t

types and properties of, 899, 900t

Hitchings, George, 836, 838, 929

HIV. See human immunodeficiency virus

HMG. See high mobility group

HMG-CoA. See β-hydroxy-β-methylglutaryl-CoA

HMG-CoA reductase, 773

in cholesterol synthesis, 773, 773f

inhibitors of, 785, 786b–787b

regulation of, 782, 782f, 783f

HMG-CoA synthase, 773

in cholesterol synthesis, 773, 773f

in ketone body formation, 619f, 620

HO. See heme oxygenase

Hoagland, Mahlon, 1006

Hodgkin, Dorothy Crowfoot, 614b–615b

Holley, Robert, 1006, 1018

Holliday intermediate, 942

in homologous genetic recombination, 942, 943f

in meiosis, 945f, 947

resolution of, 950–951, 952f

in site-specific recombination, 950, 951f

Holliday intermediate resolvases, 945f

holoenzyme, 179

homeobox, 1062

homeodomains, 1062, 1062f

homeostasis, 498

homeotic genes, 1088, 1089, 1090f

homing, 991f, 992

homing endonucleases, 325b

Homo neanderthalensis, genome sequencing for, 333–335, 334b–335b, 336f

Homo sapiens, 333

homocysteine, 643, 809f

homocystinuria, 646t

homogentisate dioxygenase, 648f, 650

homologous genetic recombination, 940. See also DNA recombination

functions of, 941–943, 947

during meiosis, 944–948, 944f, 945f

double-strand break initiation for, 947–948

site-specific, 940, 950–951, 951f, 952f

homologous proteins, 99

homologs, 35, 99

homolytic cleavage, 472, 472f

homoplasmy, 694

homopolysaccharides, 241, 241f, 242

folding of, 243–244, 243f, 244f

fuel storage forms of, 241–242, 242f

structural roles of, 243, 243f, 244f

homotropic allosteric enzymes, 214–215, 216f

homotropic binding, 157

Hoogsteen, Karst, 274

Hoogsteen pairing, 274, 275f

Hoogsteen positions, 274

hop diffusion, of membrane lipids, 379, 379f

horizontal gene transfer, 99

hormonal regulation

of body mass

adiponectin effects in, 869, 870f

AMPK role in, 869–871, 870f

diet effects on, 871–872, 871f

endocrine functions of adipose tissue, 867–868, 867f, 868f

ghrelin, ${PYY}_{3 - 36},$ and cannabinoid effects in, 872–874, 874f

gut microbial effects on, 874–875, 875f

insulin effects in, 869

leptin effects in, 869, 869f

mTORC1 pathway in, 871, 871f, 872f

carbohydrate and lipid metabolism integration by, 570

of feeding behavior, 846–847, 847t

of fuel metabolism, 859

cortisol in, 865–866

diabetes mellitus and, 875–877

epinephrine in, 864–865, 866t

during fasting and starvation, 863–864, 864t, 865f, 866f

glucagon effects in, 862–863, 863f, 863t

insulin effects in, 859–860, 859t, 860f

pancreatic β cell insulin secretion in, 860–862, 861f, 862f

of global carbohydrate metabolism, 568–570, 569f, 570f

of glycogenolysis and glycogenesis, 565–567, 565f, 566f

of glycolysis and gluconeogenesis, 545–546, 545t, 546f

tissue-specific metabolism and, 848, 848f

adipose tissues, 851–852, 851f, 853f

blood, 857–859, 858f

brain, 855–857, 855f

liver, 848–851, 849f, 851f

muscle, 852–855, 854f, 855f, 856b–857b

of triacylglycerol synthesis, 760–762, 761f

in type 2 diabetes mellitus

insulin resistance in, 877–878, 878f

management of, 878–879, 879t

hormone cascades, 843, 845–846, 847f

hormone response elements (HREs), 445, 1083, 1083f, 1084, 1084f, 1084t

hormones, 842. See also specific hormones

blood carrying of, 857–859, 858f

bottom-up signaling by, 846–847, 847f

cellular receptors for, 842–843, 843f

chemical diversity of, 843–845

chemically diverse classes of, 843–845, 844t

NO, 843

as cholesterol derivatives, 354

general mechanisms of action, 843f

GPCR signaling by, 411, 411f

${Ca}^{2 +}$ as second messenger of, 425, 425t, 427f, 427t

cAMP as second messenger of, 416b–417b, 420, 420t, 421f. See also β-adrenergic receptors

defects in, 412

diacylglycerol and ${IP}_{3}$ as second messengers of, 425, 425t, 427f

universal features of, 431–432, 431t, 432f

guanylyl cyclase signaling by, 422b–423b

high-affinity cellular receptors, 842–843

lectin recognition of, 254

lipids as, 354

eicosanoids, 355–356, 355f

steroids, 356, 356f

vitamins A and D, 356–358, 357f, 358f

in neuroendocrine system, 842, 842f

nuclear receptor signaling by, 445, 446f

regulation by. See hormonal regulation

release of, 845–846, 846f, 847f

RTK signaling by, 434

INSR, 433–438, 433f, 434f, 436f, 438f

signaling role of, 354

top-down hierarchy of signaling by, 845–846, 846f, 847f

triacylglycerol mobilization by, 603, 604f, 605f

housekeeping genes, 36, 1056

Houssay, Bernardo, 561b

Hox genes, 1089, 1090f, 1093b

HPLC. See high-performance liquid chromatography

HREs. See hormone response elements

Hsp60 family, 132f, 133

Hsp70 family, 132, 132f

HSR1. See heat shock RNA 1

HU protein, 922, 923f, 923t

human artificial chromosomes (HACs), 891

Human Genome Project, 290, 332

human genome, sequencing of

comparisons with closest biological relatives, 329–331, 330f

evolutionary history learned from, 333–335, 334b–335b, 336f

history of, 326–327, 327f

localization of disease genes in, 331–333, 332f

types of sequences seen in, 327–329, 327f

human immunodeficiency virus (HIV), 990, 991f

protease inhibitors for, 208–209, 208f, 209f

reverse transcriptase inhibitors for, 991b

$T_{H}$ cells in, 165

humoral immune system, 164

Hunchback protein, 1088

Huntington disease, protein misfolding in, 133, 135

Hurler syndrome, 251b

hyaluronan, 245, 246f

in proteoglycan aggregates, 250, 250f

structures and roles of, 247t

hyaluronidase, 245

Hycamtin. See topotecan

hydrazine, 799b

hydride ions, electron transfers by, 490

hydrocarbon derivatives, fatty acids as, 341–344, 342t, 343f

hydrocortisone, 866

hydrogen atoms, electron transfers by, 489

hydrogen bonds, 44

in α helix, 112

in β conformation, 114, 114f

in DNA

double helix, 271

triplex DNAs, 274, 275f

homopolysaccharide folding and, 243–244, 244f, 245f

in lectin-carbohydrate interactions, 257, 257f

nucleic acid structure and, 268, 269f

protein stability and, 108–109

of water, 44–45, 44f, 45f, 46f

polar solutes and, 45, 45f, 46f, 50, 50t

hydrogen ions, hemoglobin transport of, 160–161, 160f

hydrogen peroxide, mitochondrial respiratory chain production of, 668

hydrogenation, of cooking oils, 345

hydrolases, 179t

hydrolysis, 81, 237f

of ATP

free-energy of, 479–481, 479f, 480t

hypoxia-induced inhibition of, 687, 687f

cAMP signal termination by, 415f, 417–418

of carbohydrates, 259

free-energy change of

for ATP, 479–481, 479f, 480t

for phosphorylated compounds and thioesters, 481–482, 481f, 481t, 482f

of glucose 6-phosphate, 560f

of GTP, 424f

lipid structure determination using, 363

of polysaccharides and disaccharides, for glycolysis, 522f, 523–525

of RNA, 268f

standard free-energy changes of, 469t

hydronium ions, 54, 54f

hydropathy index, 374

of amino acids, 73t

of membrane protein sequences, 374, 375f

hydropathy plots, 375f

hydrophilic molecules, 46

hydrophobic effect, 48–49, 50, 108

homopolysaccharide folding and, 243–244, 244f

in integral membrane protein attachment, 374, 374f, 375f

in lectin-carbohydrate interactions, 256–257, 257f

in membrane formation, 368f, 369

in protein folding process, 131

protein stability and, 108

hydrophobic interactions, 48, 48f, 50, 50t, 368

hydrophobic molecules, 46

hydrothermal vents, 32f

β-hydroxyacyl-ACP dehydratase (DH), 748, 749f

β-hydroxyacyl-CoA (3-hydroxyacyl-CoA), 607, 607f

β-hydroxyacyl-CoA dehydrogenase, 607, 607f

in regulation of fatty acid oxidation, 613, 616, 616f

d-β-hydroxybutyrate, 619, 619s

in diabetes mellitus, 877

formation and use of, 619–621, 619f, 620f

d-β-hydroxybutyrate dehydrogenase, 619f, 620

2-hydroxyglutarate, 595, 595f

hydroxyl radicals

DNA damage by, 283

mitochondrial respiratory chain production of, 673–674, 674f

hydroxylases, 756b

5-hydroxymethylcytidine, 266s

β-hydroxy-β-methylglutaryl-CoA (HMG-CoA), 620, 773

in cholesterol synthesis, 773, 773f

in ketone body formation, 619f, 620

4-hydroxyproline, 76, 77s

in collagen, 118, 119b

hyperammonemia, 638

hyperinsulinism of infancy, 862

hyperinsulinism-hyperammonemia syndrome, 631

hypertension, G protein defects in, 424

hypertonic solutions, 51f, 52

hyperventilation, 63

hypochromic effect, 279

hypothalamus, 845, 846f

AMPK in, 870, 871

body mass regulation by, 867, 868f

bottom-up signaling to, 846–847, 847f

top-down signaling of, 845–846, 846f, 847f

hypothalamus-pituitary system, 846f

hypotonic solutions, 51f, 52

hypoxanthine, 833, 834f, 835–836, 835f

hypoxanthine-guanine phosphoribosyltransferase, 835

hypoxia, 162, 525

ATP synthase inhibition during, 687, 687f

lactic acid fermentation during, 525

ROS production during, adaptive responses for, 687–688, 688f

hypoxia-inducible transcription factor (HIF-1), 527b, 688, 688f

hypoxic conditions, pyruvate fermentation in, 525

ethanol, 525, 525f, 530, 530f, 531–532

foods and industrial chemicals produced by, 530–532

lactic acid, 525, 525f, 526, 529b

thiamine pyrophosphate in, 530, 531f, 532t

I

I bands, 170, 171f

IAPP. See islet amyloid polypeptide

ibuprofen, prostaglandin synthesis inhibition by, 355–356, 355f, 758, 758f

ice, hydrogen bonding of, 44, 45f

idose, 233s

IF proteins. See intermediate filament proteins

${If}_{1},$ ATP synthase inhibition by, 687, 687f

IFs. See initiation factors

Ig. See immunoglobulins

IgA. See immunoglobulin A

IgD. See immunoglobulin D

IgE. See immunoglobulin E

IgG. See immunoglobulin G

IgM. See immunoglobulin M

imatinib mesylate (Gleevec), 453b, 528b

immune response, 164

cells and proteins involved in, 164–165

Salmonella typhimurium escape from, 1073, 1074f, 1074t

immune system

cellular, 165

humoral, 165

protein-ligand interactions of

analytical procedures based on, 167–168, 168f

antibody binding to antigens, 165–168, 166f, 168f

immune response cells and proteins, 164–165

immunoblot assay, 167, 168f

immunofluorescence, 320

protein localization with, 319–320, 320f

immunoglobulin A (IgA), 166

immunoglobulin D (IgD), 166

immunoglobulin E (IgE), 166, 167

in allergic response, 167

immunoglobulin fold, 165

immunoglobulin G (IgG), 165, 168f

antibody binding by, 165–166, 166f

phagocytosis of, 167, 167f

structure of, 165, 166f

immunoglobulin M (IgM), 166, 167f

immunoglobulins (Ig), 165

antigen-binding sites of, 165–167, 166f

as glycoprotein, 252

heavy chains, 165–166, 166f, 167f

recombination in, 953–955, 954f

light chains, 165–166, 166f, 167f

recombination in, 953–955, 954f

recombination of genes of, 953–955, 954f, 955f

immunoprecipitation, 320, 321f

chromatin, 904b–905b

IMP. See inosinate

importins, 1045f, 1046

in cis regulation, 1071–1073, 1072f

in trans regulation, 1071–1073, 1072f

in vitro studies, of cells, 9, 9f

inclusion bodies, 310

incretins, 846, 847t

indinavir, 209f

indirubin, 453b

induced fit, 147, 186

of hexokinase, 209–210, 210f

inducers, of lac operon, 1059

inducible genes, 1054

induction, 1054

infection, selectin role in, 254–256, 255f, 256f

inflammatory response

eicosanoid role in, 759

selectins in, 255, 255f

trans fatty acid role in, 345

influenza virus

cap-snatching by, 974–975

selectins of, 255, 256f

information pathways, 884–885

informational macromolecules, 14

ATP energy for assembly of, 485–487

inheritance, mitochondrial, 693–694, 694f

inhibition, 197, 197f

by antibiotics, 210–211, 212f, 213f

HIV treatment based on, 208–209, 208f, 209f

irreversible, 200–203, 200f, 201b–202b, 203f

reversible, 197–200, 200t

inhibitory G protein $(G_{i}),$ 420

initial rate (initial velocity, $V_{0}$ ), 189

of enzyme-catalyzed reactions, 188–190, 189f, 191f

allosteric enzymes, 215, 216f

of glucose transport, 387f, 388

initiation, 1028

of protein synthesis, 1016f, 1016t, 1023–1030, 1029f

in eukaryotic cells, 1029–1030, 1031t

three steps of, 1028–1029, 1028f, 1030f

transcription, regulation of. See gene regulation

initiation codons, 1009, 1009f

protein synthesis initiation by, 1023–1030, 1028f, 1029f, 1030f, 1031t

initiation complex, 1028–1029, 1028f, 1030f

initiation factors (IFs)

bacterial, 1028–1029, 1028f, 1031t

eukaryotic, 1029–1030, 1031t

initiator (Inr), 1078, 1079f, 1080f

INO80 family, 1075

inorganic fuels, 33–34

inorganic orthophosphate $(P_{i}),$ 475–476

in ATP hydrolysis, free-energy change for, 479–481, 479f, 480t

inorganic pyrophosphatase, 485, 734

inorganic pyrophosphate $({PP}_{i}),$ 734

inosinate (IMP), 825

in nucleotide biosynthesis, 825–827, 826f

inosine, 266s, 983f

inositol 1,4,5-trisphosphate $({IP}_{3}),$ 425, 425s

as intracellular signal, 354–355, 354f

as second messenger, 425, 425t, 427f

inositol phospholipids, 371f

Inr. See initiator

Inr sequence, 969

insects

gene drives and, 325b

recombinant protein expression in, 311–312, 311f

insertion mutation, 930

insertion sequence, 952

insertion site, 917

Insig. See insulin-induced gene protein

INSR. See insulin receptor

insulation, triacylglycerols providing, 344–345, 344f

insulin, 844

amino acid sequence of, 91, 92f

blood concentrations of relative to meal times, 873f

in body mass regulation, 869

in cholesterol regulation, 782, 782f

defective mitochondria preventing release of, 695–696, 696f

diabetes mellitus arising from defects in, 875–877

discovery of, 876b

epinephrine cross talk with, 438, 438f

feeding behavior regulation by, 847t

fuel metabolism regulation by, 859–860, 859t, 860f

in global regulation of carbohydrate metabolism, 568–570, 569f, 570f

GLUT4 response to, 389, 390b

glycolysis and gluconeogenesis regulation by, 545–546, 545t, 546f

GSK3 mediation of, 567–568, 568f

high blood glucose and, 859–860, 859t, 860f

pancreatic β cell secretion of, 860–862, 861f, 862f

phosphorylations, 437f

sensitivity to, adiponectin effects on, 869, 870f

synthesis of, 845f

triacylglycerol synthesis regulation by, 760, 761f

insulin receptor (INSR), 437f

cross talk in signaling by, 438, 438f

phosphorylation cascade initiated by, 433f, 434–435, 434f

${PIP}_{3}$ role in signaling by, 435–437, 436f, 438f

insulin receptor substrate-1 (IRS-1), 434f, 434–435, 435–437, 436f, 437f

insulin resistance

SCD role in, 754

in type 2 diabetes mellitus, 877, 878f

insulin-dependent diabetes mellitus. See type 1 diabetes mellitus

insulin-induced gene protein (Insig), 782f, 783

integral membrane proteins, 372, 373–375, 373f

caveolins, 381, 381f

hydrophobic regions of, 374, 374f, 375f

surface adhesion, signaling, and other processes of, 383–384

topology of, 374–375, 374f

amino acid sequence prediction of, 374–375, 375f, 376f

integration, 409

in GPCR signaling, 420

in neuronal signaling, 444

in signal transduction, 410f, 411

integrins, 250, 252f, 383

intercellular signals, eukaryotic gene regulation by, 1083–1084, 1083f, 1084f, 1084t

interleukins, 165

intermediary metabolism, 462, 590–591

intermediate filament (IF) proteins, 6, 8f, 117

intermediates, reaction, 181, 181f

internal guide sequence, 996

intervening sequences, 889

intestine, fat absorption in, 602–603, 602f

intracellular signals

eukaryotic gene regulation by, 1083–1084, 1083f, 1084f, 1084t

phosphatidylinositols and sphingosine derivatives as, 354–355

intrinsic factor, 615b

intrinsic pathway, 222

in blood coagulation, 221f, 222

intrinsically disordered proteins, 117, 125, 126f

intrinsically disordered regions (IDRs), 439

introns, 278f, 327, 889, 889f, 973

in bacteria, 975

in chloroplasts, 975

classes of, 975

in human genome, 327, 327f

in mitochondria, 975

retrovirus similarities to, 990f, 991–993, 991f

in RNA processing, 973

self-splicing, 975–976, 975t

spliceosomal, 977

splicing of, 975–976, 976f, 977f, 978f

transcription of, 973

invasive species, 325b

inverted repeats, 273

in DNA, 273–274, 273f

ion channels, 386. See also gated ion channels

CFTR, 396, 397b–398b

defective, 397b–398b

electrical measurement of, 401, 401f

ion movement by, 401

$K^{+} .$ See $K^{+} channels$

structure and mechanism of, 386–387, 387f

toxins targeting, 444–445

ion gradients, secondary active transport using, 398–399, 400f

ion product of water, 55

ion-exchange chromatography, 84

of proteins, 84, 85f, 86

ionic interactions

of charged solutes, 46, 46t, 47f, 50, 50t

homopolysaccharide folding and, 243–244, 244f

in membrane protein attachment, 375–376

protein stability and, 108–109

ionization

of peptides, 81–82, 81f

of water, weak acids, and weak bases

acid dissociation constants and, 57, 57f

equilibrium constants and, 54–55

pH scale and, 55–56, 55t, 56f

pure water, 54, 54f

titration curves and, 58–59, 58f, 59f

ionization constants, 57

ionizing radiation, DNA damage caused by, 281

ionophores, 399

ionotropic receptors, 444, 843, 843f

ion-selective channels, 401–402

${IP}_{3} .$ See inositol 1,4,5-trisphosphate

${IP}_{3} -gated {Ca}^{2 +} channel,$ 425

IPTG. See isopropylthiogalactoside

IREs. See iron response elements

irinotecan (Campto), 906b

irisin, 847, 847t, 879

iron, 584b–585b

in heme, 148–149, 148f, 149f

iron regulatory proteins (IRP1, IRP2), 585b

iron response elements (IREs), 585b

iron-sulfur center, 582

of aconitase, 582, 583f, 584b–585b

iron-sulfur proteins, 664

in mitochondrial respiratory chain, 664, 664f

IRP1. See iron regulatory proteins

IRP2. See iron regulatory proteins

irreversible inhibitors, 200, 200f, 201–203, 201b–202b, 203f

IRS-1. See insulin receptor substrate-1

islets of Langerhans, 860, 861f

isocitrate, 581

citric acid cycle formation of, 579f, 581–582, 583f, 584b–585b, 587f

citric acid cycle oxidation of, 579f, 582, 583f

isocitrate dehydrogenase, 582

in citric acid cycle, 579f, 582, 583f

mutations in, 595, 595f

regulation of, 593f, 594

isocitrate lyase, 735

isoelectric focusing, 88, 89f

isoelectric pH, 79

isoelectric point (pI), 79

of amino acids, 79, 80f

of proteins, determination of, 88, 89f

isolated system, 20

isoleucine, 74, 74s, 647, 650, 810, 1020s

biosynthesis of, 811f, 816f

catabolism of, 640, 640f, 647–648, 647f, 650–651, 652f, 653b, 654f

properties and conventions associated with, 73t

isomerases, 179t, 522

isomerization reactions, 474, 475f

isomers, 15f, 17–18, 17b, 17f

$Δ^{3}$ -isopentenyl pyrophosphate, 774, 787

in cholesterol synthesis, 774, 774f

isoprene, 772

in cholesterol synthesis, 773f, 774, 774f, 775f

as precursor to wide array of biomolecules, 787–788, 788f

isoprenoid compounds, 359f

isoprenylation, posttranslational, 1038

isopropylthiogalactoside (IPTG), 1060, 1060s

isoproterenol, 413s

isotonic solutions, 51f, 52

isozymes, 515

hexokinase, 539–541, 539f, 540b

LDH, 540b

ISWI family, 1075

ivacaftor, for cystic fibrosis, 398b

J

J. See flux

J segments, 954–955, 954f

Jacob, François, 274, 1058

Januvia. See sitagliptin

jasmonate, 356, 759

jaundice, 818–819

Jencks, William P., 183

jumping genes, 940–941

Jun, in cell cycle regulation, 448, 449f

K

k. See Boltzmann constant

$K^{+} channels$

ATP-gated, 861–862, 862f

structure and specificity of, 402–403, 402f

voltage-gated, 402–403

action potentials produced by, 443–444, 444f

Ka. See acid dissociation constants; association constant

Kaiser, Dale, 304

kappa light chains, 953–955, 954f

Karplus, Martin, 138b

$k_{cat},$ 192, 193t

enzyme comparisons using, 192, 193t

$K_{d} .$ See dissociation constant

$K_{eq} .$ See equilibrium constant

${K^{'}}_{eq}$ . See standard equilibrium constant

Keller, Elizabeth, 1005, 1006, 1019

Kendrew, John, 121, 127, 128, 137

Kennedy, Eugene, 580, 603, 660, 765

keratan sulfates, 246,, 246f

in proteoglycan aggregates, 250, 252f

keratin, 71f

α-keratin, structure and function of, 117–118, 117f, 117t

ketals, 234

ketoacidosis, 621, 877

β-ketoacyl-ACP reductase (KR), 748, 749f

β-ketoacyl-ACP synthase (KS), 747, 749f

β-ketoacyl-CoA, 607, 607f

β-ketoacyl-CoA transferase, 620, 620f

ketogenic amino acids, 640

α-ketoglutarate, 582, 588b

amino acid biosynthesis from, 806, 807f

amino acid conversion to, 640f, 650, 651f

as biosynthetic precursor, 590

citric acid cycle formation of, 587f

citric acid cycle oxidation of, 579f, 582–584, 583f

isocitrate oxidation to, 579f, 582, 583f

transfer of α-amino groups to, 628–630, 629f, 630f

α-ketoglutarate dehydrogenase complex, 582

in citric acid cycle, 579f, 582–584, 583f

regulation of, 593f, 594

ketohexoses, 234

ketone bodies, 619, 850, 851f

amino acid conversion to, 640–641, 640f

in diabetes mellitus, 620–621, 620f, 877

fatty acid breakdown to, 619–621, 619f, 620f

in starvation, 620–621, 620f

ketoses, 230–231, 230f

asymmetric centers of, 232, 232f

ketosis, 621, 877

ketotriose, 230

Khorana, H. Gobind, 283, 1008

kidney, aquaporins in, 400

kidney stones, 646

Kilby, B. A., 204

killer T cells. See cytotoxic T cells

kinases, 476, 477b. See also protein kinases

kinetics, 24

enzyme. See enzyme kinetics

of glucose transport, 387f, 388

King, C. G., 119b

Kinosita, Kazuhiko, Jr., 681

Klenow fragment, 920

$K_{m} .$ See Michaelis constant

Kornberg, Arthur, 561b, 916

Koshland, Daniel, 159, 186

KR. See β-ketoacyl-ACP reductase

Krainer, Adrian, 982b

Krebs, Edwin, 562b

Krebs, Hans, 574, 633

Krebs bicycle, 636–637, 636f

Krebs cycle, 574. See also citric acid cycle

KS. See β-ketoacyl-ACP synthase

KSR, 440, 441f

$K_{t} (K_{transport}),$ 388

for glucose, 387f, 388

Ku70 protein, 949, 950f

Ku80 protein, 949, 950f

Kühne, Frederick W., 178

L

l stereoisomers, of amino acids, 72

L-19 IVS, 997f

lac operon

negative regulation of, 1058–1060, 1059f

positive regulation of, 1066–1067, 1066f

Lac promoter, recombinant protein expression using, 310

β-lactam antibiotics, 211, 212f, 213f

β-lactamases, 211, 213f

lactase, 240, 523

lactase persistence, 523

lactate, 526, 874

glucose synthesis from, 533, 534f, 536, 536f

pyruvate reduction to, 526, 529b

lactate dehydrogenase (LDH), 526

isozymes of, 540b

lactic acid fermentation, 525, 525f

pyruvate as terminal electron acceptor in, 526, 529b

Lactobacillus bulgaricus, 530

lactonase, 548

in pentose phosphate pathway, 547f, 548

lactones, 236f, 237

lactose, 240, 240f

digestion of, 523

E. coli metabolism of, regulation of, 1058–1060, 1058f, 1059f, 1066–1067, 1066f

sweet taste of, 231b

lactose intolerance, 523

lactosylceramide, 350f

lacZ gene, as screenable marker, 307, 308f

ladderanes, 799b

lagging strand, 916, 916f

synthesis of, 924, 924f

Lambert-Beer law, 75b

lamin, 449

CDK phosphorylation of, 449–450

Lands cycle, 767, 770f

lanosterol, 774, 776f

Lardy, Henry, 675

large fragment, of DNA polymerase I, 920

lateral diffusion, of membrane lipids, 378f, 379–380, 379f, 380f

lauric acid, structure and properties of, 342t, 343

Lavoisier, Antoine, 465

LCAT. See lecithin-cholesterol acyl transferase

$L_{d}$ state. See liquid-disordered state

LDH. See lactate dehydrogenase

LDL. See low-density lipoprotein

LDL receptors, 780

cholesterol uptake mediated by, 781–782, 781f

leader, 1068, 1069f

leading strand, 916, 916f

synthesis of, 924, 924f

leaving groups, activating, 475–476, 476f

Leber hereditary optic neuropathy (LHON), 695

lecithin-cholesterol acyltransferase (LCAT), 780, 780f

lectins, 254, 255–256, 255f, 256f

carbohydrate interactions with, 256–257, 257f, 258f

Leder, Philip, 1008

leghemoglobin, 801

leguminous plants, nitrogen-fixing bacteria symbionts of, 797, 801, 801f

Lehninger, Albert, 580, 603, 660

Leloir, Luis, 560, 562b

Leopold, Prince, 223

leptin, 846, 867, 868f

anorexigenic peptide hormone stimulation by, 868–869, 869f

feeding behavior regulation by, 847t

gene expression triggered by, 869

leptin receptor, 867–868, 868f

Lesch-Nyhan syndrome, 835

Letsinger, Robert, 283

leu operon, 1068

leucine, 74, 74s, 647, 811

biosynthesis of, 811f

catabolism of, 640, 640f, 647–648, 647f, 651–653, 654f

properties and conventions associated with, 73t

leucine zipper, 1063–1064, 1064f

leukemia

asparagine inhibitors for, 810

protein kinase inhibitors for, 452b–453b

leukemia inhibitory factor (LIF), 1091

leukocytes, 164, 858, 858f

lectin role in movement of, 255, 255f

leukotrienes (LT), 355, 355f, 356, 759

synthesis of, 759, 759f

Levinthal, Cyrus, 131

Levinthal’s paradox, 131

Levitt, Michael, 138b

Lewis, Edward B., 1087

Lewy bodies, 135

LexA repressor, in induction of SOS response, 1068–1070, 1070f

LHCII, 705, 706f

exciton absorption by, 713

state transition and, 713, 714f

LHCs. See light-harvesting complexes

LHON. See Leber hereditary optic neuropathy

libraries, DNA, 315–316, 316f, 320f

licensing, 928

Liddle syndrome, 1049

Li-Fraumeni cancer syndrome, 454

ligand-gated ion channels, 401

ligands, 147, 148

protein interactions with. See protein-ligand interactions

receptor interactions with. See receptor-ligand interactions

ligases, 179t, 477b

light

absorption of, 701, 701f

by accessory pigments, 704f, 705

by chlorophylls, 704–705, 704f

by chloroplasts, 701–704, 702f, 703f

exciton transfer of, 705–707, 706f, 707f

by photopigments, 705f

detection of, GPCR signaling in, 429–431, 429f, 430b, 430f

firefly production of, 486b

visible, 703, 703f

light chains

immunoglobulin, 165–166, 166f, 167f

recombination in, 953–955, 954f

myosin, 169, 169f

light-dependent reactions, 700, 701f

light-harvesting complexes (LHCs), 705

lignins, 820

lignoceric acid, structure and properties of, 342t

limonene, 356

Lind, James, 118b

linear electron transfer, 708, 709f

Lineweaver-Burk equation, 191–192, 191f, 197f, 198f, 199f

linkage analysis, 331

disease gene localization using, 331–333, 332f

linkers, 304, 305f

linking number, 893, 893f

of DNA supercoils, 893–895, 894f

topoisomerases changing, 895–898, 895f, 896f, 897f, 897t, 906b

α-linoleate, 754–755, 754f, 755f

linoleate

β oxidation of, 612, 612f

synthesis of, 754–755, 754f, 755f

linoleic acid, structure and properties of, 342t

α-linolenate, 759

α-linolenic acid (ALA)

omega-3 fatty acids synthesized from, 343

structure and properties of, 342t

lipases, 345

carbohydrate analysis using, 258–259

lipid bilayer, of membranes, 367–369, 369f, 370f, 372–374

catalysis of lipid movements across, 378–379, 378f

covalent attachment of proteins to, 375–377, 376f

curvature and fusion of, 382–383, 383f, 384f

integral membrane proteins spanning, 372, 373f, 375f, 376f

lateral diffusion in, 378f, 379–380, 379f, 380f

lipids in. See membrane lipids

ordering of acyl groups in, 377–378, 377f

proteins in. See membrane proteins

sphingolipid and cholesterol rafts in, 380–382, 380f, 381f

lipid biosynthesis

cholesterol

alternative fates of intermediates in, 787–788, 788f

four stages of, 772–775, 773f, 774f, 775f, 776f

isoprene units in, 773f, 774

regulation of, 782–784, 782f, 783f, 784f, 786b–787b

eicosanoids, 755, 758–759, 758f

fatty acids. See fatty acid synthesis

membrane lipids

attachment of phospholipid head groups, 764–765, 764f

CDP-diacylglycerol in, 765–767, 766f, 768f

eukaryotic pathways to phosphatidylserine, phosphatidylethanolamine, and phosphatidylcholine, 767–768

plasmalogen, 768, 771f

precursors for, 760, 761f

sphingolipids, 770, 772f

transport to cellular membranes after, 770

steroid hormones, 785–787, 788f

triacylglycerols

glyceroneogenesis for, 762–763, 762f, 763f

hormonal regulation of, 760–762, 761f

precursors for, 760, 761f

lipid droplets, 603

LIPID MAPS Lipidomics Gateway, 363

lipid metabolism

biosynthesis. See lipid biosynthesis

carbohydrate metabolism integration with, 570

digestion of fats, 602–603

ketone body formation, 619–621, 619f, 620f

in liver, 850–851, 851f

mobilization of fats, 603, 604f, 605f

oxidation. See fatty acid oxidation

subcellular localization of, 750–751, 751f

transport of fats, 603–606, 605f, 606f

xylulose 5-phosphate as key regulator of, 543–544

lipid toxicity hypothesis, 877, 878f

lipid transfer proteins (LTPs), 370f, 371, 371f

lipidome, 14, 364

lipidomics, 363–364, 364t

lipids, 13–14

activation of, 603–606, 605f, 606f

analysis of, 361–362, 362f

categorization, 363–364, 364t

extraction, 361, 362f

identification, 362f, 363, 363f

separation, 361–362, 362f

as biologically active secondary metabolites, 360, 361f

classification of, 363–364, 364t

as cofactors

dolichols, 359f, 360

lipid quinones, 359–360

vitamins E and K, 359–360

digestion of, 602–603, 602f

fatty acids. See fatty acids

in membranes. See membrane lipids

mobilization of, 603, 604f, 605f

oxidation of. See fatty acid oxidation

as pigments, 360, 360f

as signals

eicosanoids, 355–356, 355f

hormones, 354

phosphatidylinositols and sphingosine derivatives, 354–355, 354f

steroid hormones, 356, 356f

vitamins A and D, 356–358, 357f, 358f

volatile compounds of vascular plants, 356

storage. See storage lipids

structural, 346f, 347f

galactolipids and sulfolipids, 349, 349f

glycerophospholipids, 346–348, 347f, 348f, 349f, 352, 353b

sphingolipids as, 350–351, 350f, 353b

sterols, 352, 352f

transport of, 603–606, 605f, 606f

lipoate, 576, 577f

in PDH complex, 576, 576f, 577f

lipopolysaccharides, 253, 253f

lipoprotein lipase, 602f, 603

lipoprotein particles, 603

lipoproteins, 83, 83t. See also plasma lipoproteins

liposome, 369–370

lipoxins (LX), 355, 355f, 759

liquid chromatography (LC), 95

liquid-disordered $(L_{d})$ state, 378

of lipid bilayers, 377–378, 377f

liquid-ordered $(L_{o})$ state, 377

of lipid bilayers, 377–378, 377f

lithotrophic bacteria, 798b

liver

ammonia transport to, 632–633, 632f

carbohydrate regulation in, 568–570, 569f, 570f

cholesterol delivery to, 778–779, 779f

epinephrine effects on, 864–865, 866t

in fasting state, 862–863, 863f, 863t

glucagon effects on, 862–863, 863f, 863t

glucose transporters of, 389

glutamate release of amino group in, 630–631, 632f

glycogen in, 558

hexokinase isozymes of, 539–541, 539f, 540b

insulin effects on, 859–860, 859t, 860f

ketone body formation in, 618–621, 619f, 620f

metabolic functions of, 848–851, 848f

amino acid metabolism, 850, 850f

lipid metabolism, 850–851, 851f

sugar metabolism, 849–850, 849f

in starvation state, 863–864, 864t, 865f, 866f

in well-fed state, 859–860, 859t, 860f

liver enzymes, tissue-damage assays using, 637b

liver X receptor (LXR), 783, 783f

activation of, 785

living organisms

cells of, 2–3, 2f, 3f

characteristics of, 1–2, 2f

domains of, 3, 4f

dynamic steady state of, 19–20

maintenance of, 497–498

energy and matter transformation by, 20–21, 20f, 21f

energy coupling in, 22–23, 24f

energy from electron flow in, 21

energy sources and biosynthetic precursors of, 3–5, 4f

essential chemical elements of, 10, 10f

evolution of, 30–36

evolution of, amino acid sequence information on, 96–100, 99f, 100f

hexose derivatives in, 236–237, 236f

order creation and maintenance by, 21, 21f, 22b–23b

stereospecific interactions in, 15, 18, 19f

lncRNAs. See long, noncoding RNAs

$L_{o}$ state. See liquid-ordered state

Lobban, Peter, 304

lockjaw, 383

Loeb, Jacques, 511

London forces. See van der Waals interactions

long noncoding RNAs (lncRNAs), 903, 903f, 907b, 1056, 1084, 1086

lonidamine, for cancer treatment, 527b–528b

lopinavir, 209f

lovastatin (Mevacor), 361f, 786b–787b

low blood glucose

cortisol signaling of, 865–866

glucagon counteractions of, 862–863, 863f, 863t

low-density lipoprotein (LDL), 780

in atherosclerosis, 784–785, 784f, 786b–787b

cellular uptake of, 781–782, 781f

cholesterol transport as, 778f, 778t, 779f, 779t, 780

trans fatty acid effects on, 345

LT. See leukotrienes

luciferase, 71f, 486b

luciferin, 486b

lung cancer, protein kinase inhibitors for, 452b–453b

lutein

light absorption by, 704f, 705

structure of, 704f

luteinizing hormone, lectin recognition of, 254

LX. See lipoxins

LXR. See liver X receptor

lyases, 179t

lymphatic system, 848f

lymphocytes, 3f, 164, 858, 858f

recombination in, 954–955

Lynen, Feodor, 775

lysases, 477b

lysine, 74s, 76, 647, 810

biosynthesis of, 811f

catabolism of, 640, 640f, 647–648, 647f

in general acid-base catalysis, 187f

properties and conventions associated with, 73t

lysophosphatidylcholine acyltransferases (LPCATs), 767–768, 770f

lysophospholipase, 352

lysosomal storage diseases, 353b

lysosomes, 6, 7f

phospholipid and sphingolipid degradation by, 352, 353b

protein targeting to, 1043–1044, 1044f

lysozyme, 123t, 244

mechanism of, 210–213

lyxose, 233s

M

M line, 170, 171f

M phase, 446, 447f

M1 RNA, 997

MacLeod, Colin, 270

MacLeod, J. J. R., 876b

macrocytes, 643

macromolecules, 9f, 12–14, 18f

of cells, 8–9, 9f, 12–14, 14t, 15t

in water, structure, and function and, 49–51, 50f, 50t, 51f

macrophages, 164

phagocytosis of bound antibodies by, 167, 167f

mad cow disease. See bovine spongiform encephalopathy

Magellan, Ferdinand, 118b

magnesium ion $({Mg}^{2 +})$

ATP binding by, 479, 480f

in Calvin cycle, 721, 725

in chlorophyll, 704f, 705

hexokinase requirement for, 515

rubisco and, 721, 721f

major groove, 271

malaria, 256

G6PD deficiency and, 548b

hemoglobin S and, 163

malate, 587, 587f

anaplerotic reactions providing, 590, 591f

in citric acid cycle, 596f

fumarate hydration to, 579f, 587

in gluconeogenesis, 535, 535f

oxidation of, 579f, 587

from urea cycle, 634f–635f, 635, 636

malate dehydrogenase, 535

l-malate dehydrogenase, 579f, 587

malate dehydrogenase, 596f

in $C^{4}$ pathway, 729f, 731

in gluconeogenesis, 535, 535f

malate synthase, 735

malate-aspartate shuttle, 636f, 637, 684, 684f

malate–α-ketoglutarate transporter, 751–752

MALDI MS. See matrix-assisted laser desorption/ionization mass spectrometry

malic enzyme, 730, 751

in $C^{4}$ pathway, 729f, 730

NADPH generation by, 751–752, 751f

malonate, succinate dehydrogenase inhibition by, 587

malonyl/acetyl-CoA-ACP transferase (MAT), 747, 749f

malonyl-CoA, 613, 744, 745s

in fatty acid synthesis

formation of, 744–745, 745f

repeating reaction sequence using, 745–747, 746f, 747f, 748–750, 749f, 750f

in regulation of fatty acid oxidation, 613, 616, 616f

maltose, 238–239

in feeder pathways for glycolysis, 523

formation of, 237f

maltotriose, in feeder pathways for glycolysis, 523

mammalian cells, recombinant protein expression in, 312

mannosamine, 236, 236f

mannose, 232, 232f, 233s, 1044f

in feeder pathways for glycolysis, 522f, 524–525

mannose 6-phosphate, lectin interactions with, 257, 257f

mannuronic acid, 237

MAP kinase kinase kinases (MAPKKKs), 435

MAP kinase kinases (MAPKKs), 435

MAPK (mitogen-activated protein kinases), 435, 437f

MAPK cascades, 434f, 435

multivalent adaptor proteins involved in, 440, 441f

MAPKKKs. See MAP kinase kinase kinases

MAPKKs. See MAP kinase kinases

MAPKs. See mitogen-activated protein kinases

maple syrup urine disease, 646t, 652–653, 654f

mapping, denaturation, 916

Maquat, Lynne, 980

MARCKS, membrane attachment of, 375–376

maresins, 759

Margulis, Lynn, 34

mass spectrometry (MS), 93–95

amino acid sequencing with, 93–95, 94f, 95f

carbohydrate analysis using, 259

lipid analysis using, 362f, 363, 363f

protein function and, 317t, 319

mass-action ratio (Q), 24, 470, 501, 687

in metabolic regulation, 502t

mast cells, in allergic response, 167

MAT. See malonyl/acetyl-CoA-ACP transferase

maternal genes, 1087, 1088, 1089f

maternal mRNAs, 1087

matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS), 94

matter, transformation of, by living organisms, 20–21, 20f, 21f

Matthaei, Heinrich, 1007

Maxam, Allan, 286

maximum velocity $(V_{max}),$ 189

of enzyme-catalyzed reactions, 189–191, 189f, 191f

allosteric enzymes, 215, 216f

determination of, 191

interpretation of, 192–193, 192t, 193t

reversible inhibitor effects on, 198–199, 200t

of glucose transport, 387f, 388

MCAD. See medium-chain acyl-CoA dehydrogenase

McCarty, Maclyn, 270

McClintock, Barbara, 328, 940–941

McElroy, George, 653b

McElroy, William, 486b

MCM proteins. See minichromosome maintenance

MDR1. See multidrug transporter

mechanical work, muscle production of, 852–855, 854f, 855f, 856b–857b

mechanism-based inactivators, 200, 201b–202b

meclofenamate, prostaglandin synthesis inhibition by, 355

Mediator, 1079, 1080f

medicine, genomic comparisons in, 36

medium-chain acyl-CoA dehydrogenase (MCAD), 608, 616

genetic defects in, 616–617

megaloblastic anemia, 643

megaloblasts, 643

meiosis, 944

crossing over in, 945f, 946, 946b

fetal, errors in, 946b

homologous genetic recombination during, 944–948, 944f, 945f

double-strand break initiation for, 947–948

process of, 944, 944f

MEK, in INSR signaling, 434f, 435

melanin, 648

α-melanocyte-stimulating hormone (α-MSH), 868, 869f

Mello, Craig, 1085

melting point

of DNA, 278–280, 280f

of fatty acids, 342t, 343, 345f

of water, 44–45

membrane lipids, 346, 347f

characteristic, 367, 369f

galactolipids and sulfolipids, 349, 349f

glycerophospholipids

as derivatives of phosphatidic acid, 346–348, 347f, 348f

ether-linked fatty acids in, 349, 349f

lysosome degradation of, 352, 353b

hop diffusion of, 379, 379f

lateral diffusion of, 378f, 379–380, 379f, 380f

ordered states of, 377–378, 377f

sphingolipids

abnormal accumulations of, 353b

as derivatives of sphingosine, 350–351, 350f

lysosome degradation of, 352, 353b

rafts of, 380–382, 380f, 381f

as sites of biological recognition, 351

transbilayer movement of, 378, 378f

sterols, 352

lipid bilayer fluidity and, 378

rafts of, 380–382, 380f, 381f

transbilayer movement of, 378–379

synthesis of

attachment of phospholipid head groups, 764–765, 764f

CDP-diacylglycerol in, 765–767, 766f, 768f

eukaryotic pathways to phosphatidylserine, phosphatidylethanolamine, and phosphatidylcholine, 767–768

plasmalogen, 768, 771f

precursors for, 760, 761f

sphingolipids, 770, 772f

transport to cellular membranes after, 770

transbilayer movement of, 378–379, 378f

membrane potential $(V_{m}),$ 385

in electrical signaling, 442–443, 443f

in neuronal signaling, 443–444, 444f

solute movement and, 385, 385f

membrane proteins, 117

amphitropic, 372, 373f

reversible associations of, 376

characteristics of, 367, 369f

membrane bilayer of, 372–374

in cholesterol-sphingolipid rafts, 380–382, 380f, 381f

as enzymes, 371–372

integral, 372–375, 373f

amino acid sequences of, 374–375, 375f, 376f

caveolins, 381, 381f

hydrophobic regions of, 374, 374f, 375f

surface adhesion, signaling, and other processes of, 383–384

topology of, 374–375, 374f, 375f, 376f

lateral diffusion of, 380, 380f

orientation of, 369, 369f

peripheral, 372, 373f

covalent attachment of, 375–377, 376f

as receptors, 371–372

as transporters, 371–372

transporters. See transporters

membrane trafficking, 370–371, 370f, 770

membrane-bound electron carriers, in mitochondrial respiratory chain, 662–665, 663f, 664f, 664t, 665f

membranes

of chloroplasts, 702f, 704

composition and architecture of

amphitropic proteins, 372, 373f, 376

characteristic lipids and proteins, 367, 369f

fundamental properties, 369, 369f

integral membrane proteins, 372, 373f, 374f, 375f, 376f

lipid bilayer, 367–368, 369f, 370f

peripheral membrane proteins, 372, 373f, 375–377, 376f

dynamics of

catalysis of transbilayer lipid movements, 378–379, 378f

clustering of sphingolipids and cholesterol in rafts, 380–382, 380f, 381f

lateral diffusion of lipids and proteins in bilayer, 379–380, 379f, 380f

membrane curvature and fusion processes, 382–383, 383f, 384f

ordering of acyl groups in bilayer, 377–378, 377f

surface adhesion, signaling, and other processes of integral proteins, 383–384

functions of, 367

of mitochondria, 660, 661f

rafts in

signaling protein segregation by, 442

sphingolipids and cholesterol in, 380–382, 380f, 381f

solute transport across

by ABC transporters, 395–396, 396f, 396t, 397b–398b

by active transport. See active transport

by aquaporins, 400–401, 400t

by chloride-bicarbonate exchanger, 389–392, 391f

by cotransport, 389–392, 398–399

by GLUT1, 387–389, 387f, 388f, 389f, 389t

by ion channels, 397b–398b, 401–402, 401f, 402f

ion gradients driving, 398–399, 400f

by $K^{+}$ channels, 402–403, 402f

in metabolic regulation, 499f

by passive transport. See passive transport

by P-type ATPases, 392–394, 393f, 394f

by secondary active transport, 398–399

transporter and ion channel structures and mechanisms for, 386–387, 387f

types of, 385–386, 385f

by V-type and F-type ATPases, 394–395, 395f

structural lipids in, 346–354

membranous organelles, of eukaryotic cells, 6, 7f

memory B cells, 166

memory cells, 165

Menten, Maud, 189–190

menthol, 356

Mering, Josef von, 876b

MERRF. See myoclonic epilepsy with ragged-red fiber syndrome

Merrifield, R. Bruce, 96

Meselson, Matthew, 915

Meselson-Stahl experiment, 915–916

mesophyll cells, 729–731, 729f

messenger ribonucleoprotein (mRNP) complex, 973

messenger RNAs (mRNAs), 264, 960

alternative splicing of, 981–983, 983f

artificial templates of, genetic code cracking using, 1007–1009, 1007f, 1008t, 1009f, 1010b–1011b, 1012t

codons in. See codons

degradation rate of, 986–988, 987f

in DNA microarrays, 322f

editing of, 1013, 1013f, 1014f, 1015f

$5'$ cap of, 973, 974f

maternal, 1087

in metabolic regulation, 499f

polypeptide coding of, 274–275, 276f

primary transcript for, 972–973, 973f

processing of, 981f

RNA polymerase II synthesis of, 967–968

Shine-Dalgarno sequence in, 1028–1029, 1028f, 1030f

sRNA regulation of, 1071–1073, 1072f

structure of, 274–275, 276f

$3'$ end of, 980–981, 980f

translational repression of, 1084–1085, 1085f

metabolic acidosis, glutamine metabolism and, 631–632

metabolic control, 501

metabolic control analysis, 731b

metabolic pathways, 26–27, 462, 463–464, 463f. See also specific pathways

AMPK coordination of, 869–871, 870f

flux through. See flux

multidimensional network of, 497f

regulation of, 496–503, 497f

dynamic steady state, 497–498

enzymes and, 498–501

metabolic regulation, 463–464, 496–497, 497f, 501

adenine nucleotides in, 502–503, 503t

of amino acid biosynthesis, 814–816, 816f

AMPK coordination of catabolism and anabolism, 869–871, 870f

carbohydrate and lipid metabolism integration, 570

of cellular respiration pathways, 688–689, 689f

of citric acid cycle

allosteric and covalent regulation of PDH complex, 593–594, 593f

defects in, 594–595, 595f

at exergonic steps, 594

substrate channeling, 595, 595f, 596f

enzyme regulation in, 498–501, 499f, 499t, 500f, 500t, 501f

of fatty acid oxidation, 613, 616, 616f

transcription factors regulating proteins for lipid catabolism, 616

of fatty acid synthesis, 752–753, 753f

of fuel metabolism, 859

cortisol in, 865–866

diabetes mellitus and, 875–877

epinephrine in, 864–865, 866t

during fasting and starvation, 863–864, 864t, 865f, 866f

glucagon effects in, 862–863, 863f, 863t

insulin effects in, 859–860, 859t, 860f

pancreatic β cell insulin secretion in, 860–862, 861f, 862f

global regulation of carbohydrate metabolism, 568–570, 569f, 570f

glycogenolysis and glycogenesis coordination

allosteric and hormonal regulation of glycogen phosphorylase, 565–567, 565f, 566f

allosteric and hormonal signals in global carbohydrate metabolism, 568–570, 569f, 570f

GSK3 mediation of insulin, 567–568, 568f

phosphorylation and dephosphorylation of glycogen synthase, 565–567, 567f, 568f

PP1 role in, 568, 569f

glycolysis and gluconeogenesis coordination, 539

ATP in allosteric inhibition of pyruvate kinase, 544, 544f

conversion of pyruvate to phosphoenolpyruvate, 544–545, 544f

fructose 2,6-bisphosphate in allosteric regulation of PFK-1 and FBPase-1, 542, 543f

hexokinase isozyme responses to glucose 6-phosphate, 539–541, 539f, 540b

reciprocal regulation of phosphofructokinase-1 and fructose 1,6-bisphosphatase, 541–542, 541f, 542f

transcriptional regulation of number of enzyme molecules, 545–546, 545t, 546f

xylulose 5-phosphate as key regulator in, 543–544

hormonal. See hormonal regulation

neuroendocrine system role in, 842, 842f

nucleotide biosynthesis, 826f, 827–829, 829f

of oxidative phosphorylation

adaptive responses reducing ROS production in hypoxia, 687–688, 688f

by cellular energy needs, 687

coordinated regulation of ATP-producing pathways, 688–689, 689f

hypoxia-induced inhibition of ATP hydrolysis, 687, 688f

reaction equilibria and, 501–502, 502t

regulation of, 26

steady state maintenance in cells and organisms, 497–498

studies of. See metabolic control analysis

of urea cycle, 637–638, 638f

metabolic syndrome, 877, 878f

management of, 878–879, 879t

metabolic water, from fatty acid oxidation, 609

metabolism, 27, 462

ATP, role in, 26f

of autotrophs and heterotrophs, 461–462, 462f

as multidimensional network of pathways, 497f

pathways of, 26–27, 461–464, 463f. See also specific pathways

AMPK coordination of, 869–871, 870f

flux through. See flux

multidimensional network of, 497f

regulation of, 27. See also metabolic regulation

tissue-specific, 848, 848f

adipose tissues, 851–852, 851f, 853f

blood, 857–859, 858f

brain, 855–857, 855f

liver, 848–851, 850f, 851f

muscle, 852–855, 854f, 855f, 856b–857b

metabolite pools, 738, 738f, 739

metabolites, 2, 462

blood carrying of, 857–859, 858f

common cellular, 11–12

metabolome, 12, 499, 500f

metabolomics, 12

metabolons, 595

in urea cycle, 636

metabotropic receptors, 444, 843, 843f

metal ion catalysis

enolase, 210, 211f

enzymatic, 187–188

metalloproteases, 208

metalloproteins, 83, 83t

metamerism, 1087

metformin (Glucophage), 879t

methane, oxidation of, 490f, 580

methanogens, 798b, 1025b–1027b

methanol

lipid extraction using, 361, 362f

poisoning by, 198

methionine, 74, 74s, 641–642, 643f, 650, 810

biosynthesis of, 811f

catabolism of, 640f, 650–651, 652f, 653b

properties and conventions associated with, 73t

protein synthesis initiation by, 1023–1030, 1028f, 1029f, 1030f, 1031t

methionine adenosyl transferase, 641, 643f

methionine synthase, 643, 643f

methotrexate, 836, 836f

1-methyladenine, 937–938, 939f

$N^{6} -methyladenosine,$ 266s

ω-N-methylarginine, 77s

methylation, 216, 217f

carbohydrate analysis using, 258–259

of DNA, 283

of guanine, 283

of histones, 1075–1077, 1076t

of messenger RNAs, 984, 984f

in mismatch repair, 932–933, 933f, 934f

of transfer RNAs, 985, 985f

5-methylcytidine, 266s

3-methylcytosine, 937–938, 939f

methylglutamate, 1038f

methylglyoxal, 646, 646s

$N^{2} -methylguanosine,$ 266s

7-methylguanosine, 266s

1-methylguanosine, 983f

6-N-methyllysine, 77s

methyllysine, 1038f

methylmalonic acidemia (MMA), 646t, 650–651, 653b

methylmalonyl-CoA, 612, 613, 613f

methylmalonyl-CoA epimerase, 613, 613f

methylmalonyl-CoA mutase, 613, 613f

$5' -deoxyadenosylcobalamin$ as cofactor of, 614b–615b

Met-tRNA synthetase, 1024

Mevacor. See lovastatin

mevalonate, 773

in cholesterol synthesis, 773–774, 773f

MFP. See multifunctional protein

MFS. See major facilitator superfamily

${Mg}^{2 +} .$ See magnesium ion

MGDGs. See monogalactosyldiacylglycerols

micelles, 48, 48f, 368, 368f

Michaelis, Leonor, 189–190

Michaelis constant $(K_{m}),$ 190–191, 191f

determination of, 191, 194

enzyme comparisons using, 193–194, 193t

interpretation of, 192–194, 192t, 193t

metabolic regulation and, 499f, 500f

reversible inhibitor effects on, 198–199, 200t

Michaelis-Menten equation, 190, 191–192, 191f

in bisubstrate reactions, 194–195, 194f

for competitive inhibitor, 197–198

for mixed inhibitor, 198

for uncompetitive inhibitor, 198

Michaelis-Menten kinetics, 191, 192

microarrays, DNA, 322f

microdomains, 380

cholesterol-sphingolipid, 380, 380f, 381f

Micronase. See glyburide

microorganisms, signaling in, 447f

microRNAs (miRNAs), 985, 986, 986f

gene regulation by, 1085–1086, 1086f

synthesis and processing of, 986f

microtubules, 6, 8f, 169

Miescher, Friedrich, 270

mifepristone (RU486), 445, 445s

mineralocorticoids, 785

synthesis of, 785–787, 788f

minichromosome maintenance (MCM) proteins, 928

Minkowski, Oskar, 876b

minor groove, 271

miRNAs. See microRNAs

mirror repeats, in DNA, 273, 274f

mismatch repair, 931–934, 931t, 933f, 934f, 935f

missense mutations, 1013

Mitchell, Peter, 659, 668, 675

mitochondria, 6, 7f

acetate shuttling out of, 751–752, 752f

acetyl-CoA oxidation in. See citric acid cycle

anatomy of, 660, 661f

apoptosis triggering in, 691, 692f

in cardiac muscle, 855, 855f

chemiosmotic mechanisms in, 702f

damage to, 688, 693–696

diabetes mellitus caused by defects in, 695–696, 696f

in endomembrane system, 370, 370f

evolution of, 34, 35f, 692–693, 693f

fatty acid oxidation in. See fatty acid oxidation

fatty acid transport into, 603–606, 605f, 606f

genes of

mutations in, 693–696, 694f, 695f, 696f

origin of, 692–693, 693f

genome of, 301, 692, 692t, 693f

heat production by, 689–690, 690f

introns in, 975

NADH shuttling into, 636f, 637, 683–684, 684f, 686f

oxidative phosphorylation in. See oxidative phosphorylation

plant, NADH oxidation in, 685b

pyruvate oxidation in, 575, 576f, 577f, 578f

steroid synthesis in, 690–691, 690f

mitochondrial DNA (mtDNA), 887, 889f

genetic code variations in, 1010b

mitochondrial donation, 695

mitochondrial encephalomyopathies, 695

mitochondrial membranes, composition of, 367, 369f

mitochondrial pyruvate carrier (MPC), 575, 594

mitochondrial respiration, 727

mitochondrial respiratory chain, 672f

electron donation via ubiquinone, 671, 672f

electron funneling to universal electron acceptors, 660–662, 662t

electron passage through membrane-bound carriers, 662–665, 663f, 664f, 664t, 665f

genes encoding proteins of, 692, 692t, 693f

mitochondria anatomy and, 660, 661f

multienzyme complexes of electron carriers involved in

Complex I, 665–667, 665t, 666f

Complex II, 665t, 666f, 667–668, 667f

Complex III, 665t, 666f, 668–669, 668f, 669f

Complex IV, 665t, 666f, 669–671, 670f, 688, 688f

NADH oxidation in plant mitochondria, 685b

protein components of, 665t

proton gradient in, 672, 673f

respirasomes in, 671, 671f

ROS generation by, 668, 673–674, 674f

mitophagy, 660

mixed inhibitor, 199, 199f

mixed-function oxidases, 477b, 754, 756b

desaturation of fatty acids by, 754–755, 755f, 756b–757b

mixed-function oxygenases, 649, 756b

MMA. See methylmalonic acidemia

Modrich, Paul, 931

modular proteins, 409

modularity, in signal transduction, 409, 410f

modulators, 157

of allosteric enzymes, 214–215, 214f, 215f

MODY. See maturity-onset diabetes of the young

molecular asymmetry, 16f

molecular biology, 884

molecular function, 317

molecular mass, 13b

molecular motors. See motor proteins

molecular weight, 13

of polysaccharides, 241

of proteins, estimation of, 88, 88f

molecules, interactions among, 9

monensin, 399

monocistronic mRNA, 275, 276f

monoclonal antibodies, 167

protein kinases inhibitors, 452b–453b

Monod, Jacques, 10, 158, 274, 1058

monogalactosyldiacylglycerols (MGDGs), 349f

monomers, 556

monooxygenases, 477b, 756b

P-450, 756b–757b

steroid synthesis by, 690–691, 690f, 756b

monosaccharides, 229

asymmetric centers of, 232, 232f

cyclic structures of, 232f, 233–235, 234f, 236f

hexose derivatives in living organisms, 236–237, 236f

as reducing agents, 237, 238b–239b

symbols and abbreviations for, 240t

two families of, 230–231, 230f

monotopic integral membrane proteins, 372, 373f

monounsaturated fatty acids

β oxidation of, 611, 612f

double bonds in, 342

moonlighting enzymes, 584b

aconitase as, 584b–585b

Moore, Melissa, 980

morphogens, 1087

motifs, 123

classification based on, 125–126, 127f

DNA-binding, 1060–1063, 1060f, 1062f, 1063f

of globular proteins, 123–124, 123f, 124f, 125f

motor proteins, in muscle

interactions of, 170–172, 172f

myosin and actin, 169–170, 169f

proteins organizing thin and thick filaments, 169–172, 171f

movement

ATP energy for, 483, 487

motor proteins effecting

interactions of, 170–172, 172f

myosin and actin, 169–170, 170f

proteins organizing thin and thick filaments, 169–172, 171f

muscle metabolism for, 852–855, 854f, 855f, 856b–857b

MPC. See mitochondrial pyruvate carrier

mRNAs. See messenger RNAs

MS. See mass spectrometry

α-MSH. See α-melanocyte-stimulating hormone

MS/MS. See tandem Ms

mtDNA. See mitochondrial DNA

mTOR, 871

mTORC1, 871

growth regulation by, 871, 871f, 872f

mucins, 251

mucopolysaccharides. See glycosaminoglycans

mucopolysaccharidoses, 251b

Mullis, Kary, 283

multidrug transporter (MDR1), 396

multienzyme complexes. See also specific complexes

in citric acid cycle, 595, 595f, 596f

in mitochondrial respiratory chain

Complex I, 665–667, 665t, 666f

Complex II, 665t, 666f, 667–668, 667f

Complex III, 665t, 666f, 668–669, 668f, 669f

Complex IV, 665t, 666f, 669–671, 670f, 688, 688f

in respirasomes, 671, 671f

in urea cycle, 636

multimer, 127

multiple cloning site (MCS), 304

multiplicity of infection (MOI), 326f

multipotent stem cells, 1091

multisubunit proteins, 82

multivalent adaptor proteins, 439–442, 439f, 441f

muscle

ammonia transport from, 632–633, 632f

carbohydrate regulation in, 568–570, 569f, 570f

glycogen in, 557, 558

hexokinase isozymes of, 539–541, 539f, 540b

insulin effects on, 859–860, 859t, 860f

metabolic functions of, 852–855, 854f, 855f, 856b–857b

muscle contraction

ATP energy for, 483, 487

glycolysis and, 560

lactate production, 526

motor proteins involved in

interactions of, 170–172, 172f

myosin and actin, 169–170, 170f

proteins organizing thin and thick filaments, 169–172, 171f

muscle metabolism for, 852–855, 854f, 855f, 856b–857b

regulation of, 171, 172f, 427

muscle fibers, 170, 171f

mutarotation, 235

mutases, 522

mutations, 30, 31f, 280, 886, 930

cancer-causing, 930, 931f, 932b

deletion, 930, 952f

disease caused by. See genetic disease

in error-prone translesion DNA synthesis, 932b, 938–940, 939f

evolution through, 30, 31f

genetic code resistance to, 1012–1013

of HIV, 990

insertion, 930

mechanism of, 939f

in mitochondrial genes, 693–696, 694f, 695f, 696f

nonenzymatic transformations, 280–283, 281f, 282f

with nonhomologous end joining, 948–950, 950f

in oncogenes, 451, 452b–453b, 454

in promoters, 963

silent, 930

SNPs, 328

in human genome, 328

substitution, 930

in tumor suppressor genes, 454f, 455

MutH protein, in mismatch repair, 932, 934, 934f

MutL protein, in mismatch repair, 932, 934, 934f

MutS protein, in mismatch repair, 933–934, 934f

MWC model, 158, 160f

mycoplasma, 3

myelin sheath, composition of, 367

myocardial infarction

LDH isozymes as markers of, 540b

liver enzyme assays for, 637b

myoclonic epilepsy with ragged-red fiber syndrome (MERRF), 695, 695f

myocytes, 852

glucose uptake by, 390b

myofibrils, 170, 171f

myoglobin, 82t

function of, 149

heme in, 148–149, 148f

hemoglobin subunit similarities to, 153–155, 153f, 154f

oxygen binding by, 149, 149f

Hill plot for, 157, 160f

quantification of, 150f, 152

residues, 123t

structure of, 121–123, 122f, 137

binding effects of, 152–153, 153f

x-ray crystallography of, 137

myosin, 169

actin thin filament interactions with, 170–172, 172f

CDK phosphorylation of, 450

in muscle contraction, 487

structure of, 169, 169f

myristic acid, structure and properties of, 342t

myristoylation, 217f

myxothiazol, 667t

N

${Na}^{+} channels$

in neuronal function, 402

structure and specificity of, 402

voltage-gated, action potentials produced by, 443–444, 444f

${Na}^{+} -glucose$ symporter, 398, 399, 399f

${Na}^{+} K^{+}$ ATPase, 394

ATP energy for, 487

in electrical signaling, 442–443, 443f

structure and mechanism of, 392–394, 393f, 394f

${Na}^{+} {-K}^{+} - 2 {Cl}^{-}$ cotransporter 1 (NKCC1), 633

NAD. See nicotinamide adenine dinucleotide

NADH dehydrogenase, 607, 607f, 608f, 609, 665t, 666, 666f, 667

NADH:ubiquinone oxidoreductase, 665, 665t, 666–667, 666f

NADP. See nicotinamide adenine dinucleotide phosphate

nalidixic acid, 906b

nanos gene, 1088

naproxen, 758f

native conformation, 29, 107

natural selection, 30

NBD. See nucleotide-binding domain

ncRNAs. See noncoding RNAs

Neanderthals, genome sequencing for, 333–335, 334b–335b, 336f

negative regulation, 1057, 1058f

of galactose metabolism genes in yeast, 1081, 1081f, 1082t

of lac operon, 1058–1060, 1059f

negative supercoiling, 894, 894f

negatively charged R groups, 74f, 76

nelfinavir, 209f

neonatal diabetes mellitus, 862

nephron, aquaporins in, 400

Nernst equation, 491

nervous system, signaling in, 443–444, 444f

Neu5Ac. See N-acetylneuraminic acid

neuroendocrine system, 842, 842f. See also hormones

bottom-up signaling in, 846–847, 847f

major glands of, 845, 846f

top-down signaling in, 845–846, 846f, 847f

neuroglobin, function of, 149

neurons

energy supply to, 855–857, 855f

gated ion channels in

action potentials produced by, 443–444, 444f

toxins targeting, 444–445

neurotransmitters in, 443–444, 444f

neuropeptide Y (NPY), 847, 847t, 868, 869f

neurotransmitters

biosynthesis of, 821–822, 823f

in neuronal signaling, 443–444, 444f

neutral fats. See triacylglycerols

neutral glycolipids, 350f, 351

neutral pH, 55

neutrophil elastase, 220

Nexavar. See sorafenib

next-generation sequencing, 290–293, 292f, 293f

NF1 gene, in cancer, 423

N-glycosyl bond, 251

$n_{H} .$ See Hill coefficient

NHEJ. See nonhomologous end joining

niacin (nicotinic acid), 495s

deficiency of, 494, 495f

niche, 1091

nick translation, 920, 920f

nicotinamide adenine dinucleotide (NAD, ${NAD}^{+},$ NADH), 295f, 295s

deficiency of, 494, 495f

as enzyme substrate, 494

in gluconeogenesis, conversion of pyruvate to phosphoenolpyruvate, 534–537, 535f, 536f

glycerol 3-phosphate shuttle for, 684, 686f

in glycolytic pathway, 512f, 513, 513f, 518–521, 520f, 525f

coupling of, 513–514

malate-aspartate shuttle for, 636f, 637, 684, 684f

in mitochondrial respiratory chain, 660–662, 662t, 664t

in PDH complex, 576

plant oxidation of, 685b

regeneration of, by fermentation, 525

as soluble electron carrier, 493–494, 493f

nicotinamide adenine dinucleotide phosphate (NADP, ${NADP}^{+},$ NADPH)

in Calvin cycle, 720f, 721

requirements of, 722–724, 724f

source of, 719, 726f

deficiency of, 494, 495f

in fatty acid synthesis, 745, 746f, 749f, 750–751, 751f

in mitochondrial respiratory chain, 660–662, 662t, 664t

in pentose phosphate pathway, 547–548, 547f, 548b

glucose 6-phosphate partitioning between glycolysis and, 551, 551f

in photosynthesis, 709

Z scheme, 709

as soluble electron carrier, 493–494, 493f

nicotinamide nucleotide-linked dehydrogenases, 661

nicotinic acid. See niacin

Niemann-Pick disease, 353b

Niemann-Pick type-C (NPC) disease, 782

night blindness, G protein defects in, 424

NIH shift, 649f

Nirenberg, Marshall, 1007, 1008

nitrate assimilation, 796, 796f

nitrate reductase, 796, 796f

nitric oxide (NO), 423b

arginine in biosynthesis of, 822, 824f

hormone functions of, 843

nitrification, 795, 795f

nitrite reductase, 796, 796f

nitrogen, 626

nitrogen cycle, 462, 462f

biologically available nitrogen in, 795–796, 795f, 796f, 798b–799b

nitrogen excretion, urea cycle and, 633

citric acid cycle links to, 636–637, 636f

defects in, 638–639, 638t, 639f

enzymatic steps of, 633–636, 634f–635f

pathway interconnections reducing energetic cost of, 638

reactions feeding amino groups into, 634f–635f

regulation of, 637–638, 638f

nitrogen fixation, 795–802, 795f, 797f, 800f, 801f

nitrogen metabolism, 795

amino acid biosynthesis. See amino acid biosynthesis

amino acid catabolism. See amino acid catabolism

amino acid derivatives

biological amines, 821–822, 823f, 824f

creatine and glutathione, 819–820, 821f

NO, 822, 824f

plant substances, 820–821, 822f

porphyrins, 817–821, 817f, 819b, 820f

ammonia assimilation into glutamate and glutamine, 802–803

glutamine synthetase in regulation of, 803–804, 803f, 804f

nitrogen cycle and, 462, 462f

biologically available nitrogen in, 795–796, 795f, 796f, 798b–799b

nitrogen fixation, 795–802, 795f, 797f, 800f, 801f

nucleotide biosynthesis. See nucleotide biosynthesis

nucleotide catabolism

salvage pathways, 835

urea produced by, 833–835, 834f, 835f

uric acid produced by, 833–836, 834f, 835f

nitrogenase complex, 797

nitrogen fixation by, 797–802, 797f, 800f, 801f

nitrogenous bases, 264–267, 264f, 265t

alkylated, 938, 939f

biosynthesis of

purines, 825–827, 825f, 826f, 835

pyrimidines, 828f, 829, 829f, 835

conformations of, in DNA, 272–273, 272f, 273f

degradation of

purines, 833–836, 834f, 835f

pyrimidines, 833–835, 834f, 835f

methylation of, 283

nonenzymatic transformations of, 280–283, 281f, 282f

nucleic acid structure and, 268, 269f

origin of, 999f

pairing of, 267, 269f

in codon and anticodon recognition, 1010–1012, 1012f, 1012t

in DNA replication, 918f, 919f

DNA stability and, 280

DNA structure determination and, 270–271, 271f

Hoogsteen, 274, 275f

in transcription, 963

in replication, 918f

nitroglycerin, for angina pectoris, 423b

nitrous acid, DNA damage caused by, 282, 282f

nitrovasodilators, for angina pectoris, 423b

NKCC1. See ${Na}^{+} {-K}^{+} {-2Cl}^{-}$ cotransporter 1

NLS. See nuclear localization sequence

NMR spectroscopy. See nuclear magnetic resonance spectroscopy

NO. See nitric oxide

NO synthase, 423b

Nogales, Eva, 141, 142

Noller, Harry, 1006, 1017

Nomura, Masayasu, 1015

noncoding DNA, in human genome, 328

noncoding RNAs (ncRNAs), 264, 331f, 960, 985, 1056

noncompetitive inhibition, 199

noncyclic electron flow, 713

nonessential amino acids, 805

nonhomologous end joining (NHEJ), 322, 941, 948, 949, 950f

non-insulin-dependent diabetes mellitus. See type 2 diabetes mellitus

nonketotic hyperglycinemia, 646

nonpolar, aliphatic R groups, 74–75, 74f

nonpolar solutes

examples of, 46t

gases, 47, 47t

water structure effects of, 47–49, 48f, 49f, 50t

nonsense codons. See termination codons

non-small-cell lung cancer (NSCLC), 453b

nonsteroidal anti-inflammatory drugs (NSAIDs), prostaglandin synthesis inhibition by, 355–356, 355f, 758, 758f

non-stop complex, 1033b

nontemplate strand, 962, 962f

noradrenaline. See norepinephrine

norepinephrine, 428f, 821, 823f, 842, 864

novobiocin, 906b

NPC disease. See Niemann-Pick type-C disease

NPY. See neuropeptide Y

NSAIDs. See nonsteroidal anti-inflammatory drugs

N-terminal residue. See amino-terminal residue

nuclear localization sequence (NLS), 1045, 1045f

nuclear magnetic resonance (NMR) spectroscopy, 137

carbohydrate analysis using, 259

protein structure determination using, 137–139, 140f

nuclear pores, 1045, 1045f

nuclear receptors, 411, 411f, 843f

for hormones, 842–843, 843f

nucleases, 916

nucleic acids, 13

bases of, 264–267, 264f, 265t, 266f

pairing of. See base pairs

biological information in, 263

chemistry of

denaturation, 278–280, 279f, 280f

DNA amplification, 283–286, 285f, 288b–289b

DNA chemical synthesis, 283, 284f

DNA methylation, 283

DNA sequencing, 287–293, 287f, 290f, 292f, 293f

nonenzymatic transformations, 280–283, 281f, 282f

nomenclature for, 265, 265t

pentoses in, 230f, 264–267, 264f, 265t

phosphodiester linkages in, 267–268, 267f

three-dimensional structure of, 269–277

DNA double helix, 270–272, 271f, 272f

DNA variation in, 272–273, 272f, 273f

mRNAs, 274–275, 276f

nucleotide base effects on, 268, 269f

rRNAs, 276–277, 278f, 1018–1020, 1018f

tRNAs, 276–277, 276f, 278f, 1018–1020, 1019f

unusual structures adopted by DNA sequences, 273–274, 273f, 274f, 275f

types of, 263

nucleoid, 909, 909f

nucleoids, 2, 2f, 5f, 910f

nucleophiles, 207f, 473

biological, 473, 473f

nucleophilic displacement, 475–476, 475f

in ATP reactions, 484–485, 485f, 486b

lysozyme use of, 210–213

nucleoside diphosphate kinase, 487, 586

mechanism of, 487–488, 487f

nucleoside diphosphate kinases, 829

nucleoside monophosphate kinases, 829

nucleoside monophosphates, nucleoside triphosphate synthesis from, 829

nucleoside triphosphates

in cellular metabolism, 263

as chemical energy carriers, 294, 294f

nucleoside monophosphate conversion to, 829

nucleosides, 264

nucleosomes, 899

as fundamental units of chromatin, 900–902, 900f, 901f, 904b–905b

histones in, 899–900, 899f, 900f, 901f

variants, 904b–905b, 1075–1077, 1076f, 1076t

packing of, 902–905, 902f

$5' -nucleotidase,$ 833, 834f

nucleotide adapters, 1006f

nucleotide biosynthesis, 823–824

chemotherapeutic agents targeting, 836–838, 836f

conversion of nucleoside monophosphates to nucleoside triphosphates, 829

deoxyribonucleotide synthesis from ribonucleotides, 829–832, 830f, 831f, 832f

purine synthesis

de novo pathways, 825–827, 825f, 826f

regulation of, 826f, 827

salvage pathways, 835

pyrimidine synthesis

de novo pathways, 827, 828f, 829f

regulation of, 829, 829f

salvage pathways, 835

special classes of reactions in, 804–805, 804f

thymidylate synthesis, 833, 833f

nucleotide sequences

amino acid sequence relationship to, 263

amino acid sequences correlating with, 886, 886f

nucleotide sugar, 733

nucleotide-binding domain (NBD), of ABC transporters, 395, 396f, 397b

nucleotide-binding fold, 295

nucleotide-exchange factor (NEF), 132f

nucleotide-excision repair, 931t, 932b

in bacteria, 931t, 935–937, 936f

nucleotides, 264, 264s. See also specific nucleotides

bases of. See nitrogenous bases

as chemical energy carriers, 294, 294f

codon triplets of, 886, 886f, 1007, 1007f

determination of, 1007–1009, 1007f, 1008t, 1009f, 1010b–1011b, 1012t

degradation of

salvage pathways, 835

urea produced by, 833–835, 834f, 835f

uric acid produced by, 833–836, 834f, 835f

in enzyme cofactors, 294–295, 295f

flavin, 495–496, 495f

nomenclature for, 265, 265t

nonenzymatic transformations of, 280–283, 281f, 282f

in nucleic acids. See nucleic acids

pentoses of, 264–267, 264f, 265t

pyridine, 494

NAD. See nicotinamide adenine dinucleotide

NADP. See nicotinamide adenine dinucleotide phosphate

as regulatory molecules and signals, 296, 296f

structure of, 264f

sugar, in glycogenesis, 560–563, 563f

transphosphorylations between, ATP energy for, 487–488, 487f

UV light absorption by, 268, 269f, 279

nucleus, 2

in endomembrane system, 370

protein targeting to, 1045, 1045f

NusA protein, 964

NusG protein, 967

nusinersen, 982b

Nüsslein-Volhard, Christiane, 1087

O

$O_{2} .$ See oxygen

$O^{6} -methylguanine-DNA$ methyltransferase in, 938f, 939f

obesity, 867

hormonal regulation of. See body mass regulation

leptin and, 869

management of, 878–879, 879t

SCD role in, 754

type 2 diabetes associated with, 877, 878f

obligate anaerobes, 3

Ochoa, Severo, 561b, 1007–1008

odors, detection of, GPCR signaling in, 431

O-glycosidic bond, 237

Ogston, Alexander, 588b

OGT. See O-GlcNAc transferase

Okazaki fragments, 916

in DNA replication, 916, 916f

synthesis of, 924–925, 924f, 926f

oleate, β oxidation of, 611, 612f

oleic acid, structure and properties of, 342t

olfaction, GPCR signaling in, 431

oligo $(α 1 \to 6)$ to $(α 1 \to 4)$ glucantransferase, 559, 559f

oligomer, 12, 127

oligomeric proteins, 82

oligomycin, 667t

oxidative phosphorylation inhibition by, 676, 676f

oligonucleotide, 268

self-splicing introns with, 996, 996f, 997f

oligonucleotide-directed mutagenesis, 312f, 313

oligopeptide, 81

oligosaccharides, 229

analysis of, 258–260, 259f

in feeder pathways for glycolysis, 522f, 523–525

in glycoproteins, 251–253, 252f

glycosidic bond in, 240, 240t

information carried by, 247, 254

lectin reading of, 254–256, 255f, 256f

lectin-carbohydrate interactions, 256–257, 257f, 258f

nomenclature of, 240, 240t

synthesis of, 1043f

olive oil, fatty acid composition, 345f

omega-3 (ω-3) fatty acids, 343

in cardiovascular disease, 343

eicosanoid synthesis from, 755, 758–759, 758f

synthesis of, 754–755, 754f, 755f

omega-6 (ω-6) fatty acids, 343

in cardiovascular disease, 343

eicosanoid synthesis from, 755, 758–759, 758f

synthesis of, 754–755, 754f, 755f

oncogenes, 451, 452b–453b, 454

viral sources of, 451, 990, 990f

oncometabolites, 594

one gene-one enzyme hypothesis, 886

one gene-one polypeptide hypothesis, 886

open complex, 964

open reading frame (ORF), 1009

open system, 20

operators, 1057, 1058f

operons, 1058, 1058f

his, 1068

lac

negative regulation of, 1058–1060, 1059f

positive regulation of, 1066–1067, 1066f

leu, 1068

phe, 1068

r-protein, 1070–1071, 1070f, 1071f

trp, 1067–1068, 1067f, 1069f

opioid drugs, G-protein signaling actions of, 419

opsins, 429

in vision signaling, 429–431, 429f, 430b, 430f

optical activity, 16, 17b, 71

of amino acids, 71

oranelles, 6

Orbitrap, 94

ORC. See origin recognition complex

orexigenic neurons, 868, 869f

ORF. See open reading frame

organelles

in endomembrane system, 370, 370f

of eukaryotic cells, 6, 7f

membranes of, composition of, 367, 369f

movement of, 169

osmotic strength of, 53

organic compounds, 14f

Orgel, Leslie, 998

ori. See origin of replication

origin of replication (ori), 306, 916, 922f

in bacteria, 916, 916f

in eukaryotes, 928

origin recognition complex (ORC), 928, 929f

origin-independent restart of replication, 943

ornithine, 76, 77s

proline synthesis from, 806, 807f

in urea cycle, 634f–635f, 635, 636

ornithine d-aminotransferase, 807f

ornithine decarboxylase, 822

inhibition of, 201b–202b, 822

ornithine transcarbamoylase, 634

in urea cycle, 634f–635f, 635

ornithine δ-aminotransferase, 806, 808f

orotate, 824

pyrimidine ring synthesis as, 824, 828, 828f

orthologs, 99, 317

oseltamivir (Tamiflu), 255, 256f

osmolarity, 51f, 52–53, 52f

osmosis, 51–53, 51f, 52

osmotic pressure, 51–53, 51f

osteogenesis imperfecta, 120

outgroups, 330

ovarian cancer, 948b

oxaloacetate, 581, 587f

amino acid biosynthesis from, 809–811, 811f

amino acid degradation to, 640f, 653–654, 654f

in $C_{4}$ pathway, 729f, 730

in citric acid cycle, 580

acetyl-CoA condensation with, 579f, 581, 581f, 582f

anaplerotic reactions providing, 590, 591f

as biosynthetic precursor, 590

malate oxidation to, 579f, 587

in gluconeogenesis, 533f, 534–537, 535f, 536f, 544

in glyoxylate cycle, 736, 736f

oxidases, 477b, 756b

oxidation

of acetyl-CoA. See citric acid cycle

of amino acids, 630–631, 632f

of fatty acids. See fatty acid oxidation

of glucose

ATP yielded from, 589t, 686–687, 686t

electron carriers for, 492

by glycolysis. See glycolysis

by pentose phosphate pathway. See pentose phosphate pathway

of glyceraldehyde 3-phosphate, as sixth step in glycolytic pathway, 513f, 518, 525f

of methane, 580

of pyruvate, in mitochondria, 575, 576f, 577f, 578f

standard free-energy changes of, 469t

oxidation-reduction (redox) reactions, 20, 490f

biological, 476–478, 477f, 488

carbon and, 476f

dehydrogenases involved in, 493–494, 493f

dehydrogenation, 477f, 489–490

electron carriers in, 493–494, 493f

flavin nucleotides in, 495–496, 495f

free-energy change of, 491t, 492

half-reactions describing, 489

${NAD}^{+}$ functions outside of, 494–495

NADH and NADPH in, 493–495, 493f, 495f

niacin deficiency and, 494, 495f

oxidation of glucose to ${CO}_{2}$ , 492

reduction potentials for, 490–492, 491f, 491t

work provided by electron flow in, 488–489

with chlorophyll molecules, 707, 707f

lipid cofactors involved in, 359–360

oxidative deamination, 631

of glutamate, 630–631, 632f

oxidative decarboxylation, 575

conserved enzymatic mechanism for, 582, 583f

of pyruvate in PDH complex, 575, 576f

oxidative pentose phosphate pathway, 547–548, 549

oxidative phosphorylation

agents interfering with, 667t

ATP synthesis in, 659–660, 660f, 674–675

active transport energized by proton-motive force in, 683, 683f

ATP stabilization in, 677–678, 678f

ATP synthase $f_{o}$ and $f_{1}$ domains in, 677, 678f

conformations of ATP synthase β unit in, 678–680, 679f

NADH shuttle systems for, 683–684, 684f, 686f

nonintegral stoichiometries of $O_{2}$ consumption and ATP synthesis in, 682–683

oxidation and phosphorylation coupling in, 675–677, 675f, 676f, 677f

proton flow producing rotary motion in, 681–683, 681f

proton gradient driving ATP release in, 678, 678f

rotational catalysis in, 680–682, 680f, 681f

ATP yield in, 686–687, 686t

mechanism of, 659–660, 660f

mitochondrial respiratory chain in

Complex I, 665–667, 665t, 666f

Complex II, 665t, 666f, 667–668, 667f

Complex III, 665t, 666f, 668–669, 668f, 669f

Complex IV, 665t, 666f, 669–671, 670f, 688, 688f

electron donation via ubiquinone, 671, 672f

electron funneling to universal electron acceptors, 661–662, 662t

electron passage through membrane-bound carriers, 662–665, 663f, 664f, 664t, 665f

genes encoding proteins of, 692, 692t, 693f

mitochondria anatomy and, 660, 661f

NADH oxidation in plant mitochondria, 685b

proton gradient in, 672, 673f

respirasomes in, 671, 671f

ROS generation by, 668, 673–674, 674f

regulation of

adaptive responses reducing ROS production in hypoxia, 687–688, 688f

by cellular energy needs, 687

coordinated regulation of ATP-producing pathways, 688–689, 689f

hypoxia-induced inhibition of ATP hydrolysis, 687, 688f

uncoupling of, 667t, 676, 676f

oxidative stress

DNA damage by, 283

in G6PD deficiency, 548b

hypoxia leading to, adaptive responses for, 687–688, 688f

mitochondrial damage caused by, 688, 693–696

oxidative phosphorylation generation of, 668, 673–674, 674f

oxidoreductases, 179t, 494

oxygen $(O_{2})$

blood carrying of, 857–859, 858f

in chloroplasts, 701

Z scheme, 709

combination with, electron transfers by, 489

in mitochondrial respiratory chain, Complex IV, electron transfer to, 665t, 666f, 669, 670–671, 670f, 688, 688f

oxygen autotroph and heterotroph cycling of, 461–462, 462f

oxygen cycle, 461–462, 462f

oxygen esters, 483f

oxygenases, 477b, 756b

oxygen-binding proteins

cooperative binding by, 155–156, 156f, 160f, 161f

globin family, 149

heme binding of oxygen, 148–149, 148f, 149f

hemoglobin binding of carbon monoxide, 158b–159b

hemoglobin binding of oxygen, 155–156, 155f, 156f, 160f, 161–162, 162f

hemoglobin in sickle cell anemia, 162–164, 163f

hemoglobin subunit structure, 153–155, 153f, 154f

hemoglobin transport of ${CO}_{2},$ 160–161, 161f

hemoglobin transport of hydrogen ions, 160–161, 161f

hemoglobin transport of oxygen, 153

mechanistic models for, 158–160, 161f

myoglobin binding of oxygen, 149, 149f

quantitative description of binding by, 150–152, 150f, 151t, 156–157, 160f

regulation of, 161–162, 162f

structural influences on binding by, 152–153, 153f

oxygen-evolving complex, 715

structure of, 715, 715f

water-splitting activity of, 714–715, 715f

oxygenic photosynthesis, 714

oxypurinol, 835f, 836

oxythiamine, for cancer treatment, 528b

P

P cluster, 797, 797f, 800

P loop, 421, 421f, 424f

of G proteins, 423

P site. See peptidyl site

$P / 2 e^{-}$ ratio, 682

p21 protein

cell cycle regulation by, 450, 450f

mutations in, 451

p27 protein, 125

p53 protein, 125, 126f

cell cycle regulation by, 450, 450f

in tumors, 454, 455, 527b

P680 reaction center

discovery of, 709

in electron flow, 710, 712

oxygen-evolving complex and, 714–715, 715f

in photosystem II, 709f, 710

P700 reaction center

cyclic electron flow with, 713

discovery of, 709

in electron flow, 711, 712f

in photosystem I, 709f, 711

P870 reaction center

discovery of, 707–708

in Fe-S reaction center, 708, 708f

internal conversion and, 708

in pheophytin-quinone reaction center, 708, 708f

Pace, Norman, 997

Paganini, Niccolò, 120

pain treatments, 758

pair-rule genes, 1088

Palade, George, 6, 1041

palindrome, 273

DNA, 273–274, 274f

palmitate

long-chain fatty acid synthesis from, 753, 754f

synthesis of, 747f, 748–750, 750f

palmitic acid, structure and properties of, 342t

palmitoleic acid, structure and properties of, 342t

palmitoyl-CoA

β oxidation of, 607–611, 607f, 608f, 610b, 611t

in regulation of fatty acid synthesis, 752–753, 753f

pancreas, 848f

pancreatic α cells, 860, 861f

pancreatic β cells

defective mitochondria in, 695–696, 696f

insulin secretion by, 860–862, 861f, 862f

pancreatic δ cells, 860, 861f

pancreatic trypsin inhibitor, 220, 628

pancreatitis, acute, 628

paracrine hormones, 843

paraganglioma, 667–668

parallel strands, 271, 271f, 275f

paralogs, 99, 317

parasites, lectins of, 256

Parkinson disease, protein misfolding in, 133, 135

parkinsonism, protein misfolding in, 135

partial digest, 309

partial hydrogenation, of cooking oils, 345

partial pressure, 62

passive transport, 385, 385f

passive transporters, 385

chloride-bicarbonate exchanger, 389–392, 391f

GLUT1, 387–389, 387f, 388f, 389f, 389t

Pasteur, Louis, 16, 17b, 178, 525

patch-clamping, 401

of ion channels, 401–402, 401f

pathways, 26

metabolic, 26–27

Pauling, Linus, 98, 109, 111–116, 117, 183, 202

Paulze, Marie Anne, 465

Pax6 gene, 1093b

payoff phase, of glycolysis, 512f, 513, 518–521

conversion of 3-phosphoglycerate to 2-phosphoglycerate, 513f, 520, 520f

dehydration of 2-phosphoglycerate to phosphoenolpyruvate, 513f, 520–521

oxidation of glyceraldehyde 3-phosphate to 1,3-bisphosphoglycerate, 513f, 518, 525f

phosphoryl transfer from 1,3-bisphosphoglycerate to ADP, 513f, 521

transfer of phosphoryl group from phosphoenol pyruvate to ADP, 513f, 514–515

pBR322, 306, 306f, 307f

PCNA. See proliferating cell nuclear antigen

PCR. See polymerase chain reaction

PCr. See phosphocreatine

PDB. See Protein Data Bank

PDE. See phosphodiesterase

PDGFR. See platelet-derived growth factor receptor

PDH. See pyruvate dehydrogenase

PDH kinase, 594, 594f

PDH phosphatase, 594, 594f

PDI. See protein disulfide isomerase

pellagra, 494–495, 495f

penicillin, 210–211, 212f, 213f

pentose phosphate pathway, 510–511, 510f, 546, 547f

defects in, 548b, 551

glucose 6-phosphate partitioning between glycolysis and, 551, 551f

in liver, 849

nonoxidative phase of, 549–551, 549f, 550f, 719

oxidative phase of, 547–548, 547f, 551, 726

reductive, 722

pentose phosphates, movement of, 738–739, 738f

pentoses, 230f, 231

in nucleotides and nucleic acids, 264–267, 264f, 265t

PEP. See phosphoenolpyruvate

pepsin, 627–628, 628f

pepsinogen, 627, 628f

peptide bond, 81

formation of, 81, 81f, 884

$Δ G$ of, 1036

during elongation, 1031–1032, 1032f

protease cleavage of, chymotrypsin, 204–208, 204f, 205f, 206f–207f

rigid and planar nature of, 109–110, 110f

peptide group, 109, 110f

peptide hormones, 843f, 844. See also specific hormones

feeding behavior regulation by, 847t

lectin recognition of, 254

peptide prolyl cis-trans isomerase (PPI), 133

peptide translocation complex, 1042, 1042f

peptide YY $({PYY}_{3 - 36}),$ 847, 847t, 873

body mass regulation by, 872–874, 874f

peptides, 80

amino acids in, 81, 81f

chemical synthesis of, 95–96, 97f

ionization behavior of, 81–82, 81f

sizes and compositions of, 82–83, 82t, 83t

peptidoglycan

lysozyme reaction with, 210–213

penicillin interference with, 211

structure of, 244

structures and roles of, 247t

peptidyl (P) site, 1028, 1028f

peptidyl transferase, 1032, 1032f

perilipins, 603

peripheral membrane proteins, 372, 373f

covalent attachment of, 375–377, 376f

permeability, of membranes, 369, 369f

permeability transition pore complex (PTPC), 691, 692f

pernicious anemia, 615b, 643

peroxisome proliferator-activated receptors (PPARs), 871

body mass regulation by, 871–872, 871f, 872f, 873f

peroxisomes, 6, 7f, 617, 768

α oxidation in, 618, 618f

β oxidation in, 617–618, 617f, 618f

perspective diagram, 15, 15f

Perutz, Max, 127, 128, 155

PET. See positron emission tomography

PFK-1. See phosphofructokinase-1

PFK-2. See phosphofructokinase-2

PG. See prostaglandins

2-PGA. See 2-phosphoglycerate

${PGE}_{2} .$ See prostaglandin $E_{2}$

pH, 55, 60

of blood, 56b

buffering of, 59

in cells and tissues, 60f, 61–63, 62f, 63f

conjugate acid-base pair, 59–63, 60f, 62f

Henderson-Hasselbalch equation for, 60

chymotrypsin response to, 205, 205f

enzyme kinetics and, 195–196, 196f

fermentation lowering of, 532

isoelectric, 79

neutral, 55

oxygen binding effects of, 160–161, 161f

PH domain. See pleckstrin homology domain

pH optimum, 63, 63f

pH scale, 55–56, 55, 55t, 56f

phagocytosis, of bound antibodies, 167, 167f

phase variation, 1073

in Salmonella typhimurium, 1073, 1074f, 1074t

phe operon, 1068

phenotype, 886

phenotypic function, 317

phenylalanine, 74s, 75, 75f, 647, 812

biosynthesis of, 811–812, 814f

catabolism of, 640, 640f, 647–648, 647f, 648f, 649f

defects in, 646t, 647–648, 649f

plant substances derived from, 820–821, 822f

properties and conventions associated with, 73t

phenylalanine ammonia lyase, 650

phenylalanine hydroxylase, 649, 649f, 812

phenylbutyrate, for urea cycle defects, 638, 639f

phenylketonuria (PKU), 646t, 649–650, 649f

phenylpyruvate, 649, 649f

pheophytin, 708

pheophytin-quinone reaction center, 708–710

electron transfers in, 708, 708f

functional model of, 708f, 709

structure of, 708f

phosphagens, 488

phosphate, $P_{i} -triose$ phosphate antiport system and, 724–725, 724f

phosphate buffer system, 61–62

phosphate esters, 294f

phosphate translocase, 683, 683f

phosphatidic acid, 760

glycerophospholipids as derivatives of, 346–348, 347f, 348f

synthesis of, 760, 761f, 764–765, 764f

phosphatidic acid phosphatase, 760, 761f

phosphatidylcholine, 348f, 351f, 369f, 370, 765

membrane curvature and, 382

synthesis of, 767–768, 767f, 770f

transbilayer movement of, 378

phosphatidylethanolamine, 348f, 371f, 765

synthesis of, 766f, 767–768

transbilayer movement of, 378

phosphatidylglycerol, 348f, 370f, 765

synthesis of, 765, 766f, 767, 768f, 769f

phosphatidylinositol, synthesis of, 765, 768f

phosphatidylinositol 3,4,5-trisphosphate $({PIP}_{3}),$ 370f, 421f

in INSR signaling, 435–437, 436f

signaling role of, 354–355

phosphatidylinositol 4,5-bisphosphate $({PIP}_{2}),$ 348f

as intracellular signal, 354, 354f

on membranes, protein binding to, 375

phosphatidylinositol kinases, 765, 768f

phosphatidylinositol transfer proteins, 378, 379

phosphatidylinositols, as intracellular signals, 354–355, 354f

phosphatidylserine, 348f, 370f, 371f, 765

synthesis of, 765, 766f, 767–768, 767f, 769f

transbilayer movement of, 378

phosphoanhydride bonds, 294f

phosphocreatine (PCr), 487, 819

biosynthesis of, 819, 821f

free energy of hydrolysis of, 481, 481t, 482f

in muscle, 854, 854f, 856b–857b

phosphodiester bond hydrolysis, 995

phosphodiester bonds, 765f, 998

phosphodiester linkages, 267

in nucleic acids, 267–268, 267f

phosphodiesterase (PDE), 423b

in vision signaling, 429f, 430–431, 430b, 430f

phosphoenolpyruvate (PEP), 520

amino acid biosynthesis from, 811, 811f, 814f

free energy of hydrolysis of, 481, 481f, 481t

in gluconeogenesis, 534–537, 535f, 536f

in glycolysis, 512f, 513f, 520–521

in glyoxylate cycle, 736, 736f

hydrolysis of, 481f

pyruvate conversion to, 534–537, 535f, 536f

regulation of, 544–545

phosphoenolpyruvate (PEP) carboxylase, 535, 730

in $C_{4}$ pathway, 729f, 730

in gluconeogenesis, 535, 535f

in glyceroneogenesis, 762, 762f, 763f

oxaloacetate produced by, 590, 591f

phosphofructokinase-1 (PFK-1), 516

in glycolytic pathway, 513f, 516

regulation of

by citrate, 689

by fructose 2,6-bisphosphate, 542, 543f

reciprocal, 541–542, 541f, 542f

phosphofructokinase-2 (PFK-2), 542, 543f, 734, 734f

phosphoglucomutase, 522, 559, 559f

6-phosphogluconate dehydrogenase, 548

in pentose phosphate pathway, 547f, 548

phosphogluconate pathway, 546. See also pentose phosphate pathway

phosphoglucose isomerase, 515

in glycolytic pathway, 513f, 515–516, 515f

2-phosphoglycerate (2-PGA)

enolase dehydration of, 210, 211f

in glycolytic pathway, 513f, 520–521, 520f

3-phosphoglycerate, 519, 719

amino acid biosynthesis from, 806–809, 807f, 808f

in Calvin cycle, 720f, 721–722

${CO}_{2}$ fixation into, 720–721, 724f, 728f

conversion to glyceraldehyde 3-phosphate, 720f, 721–722

in glycolate pathway, 727–729, 728f

in glycolytic pathway, 513f, 520, 520f

$P_{i} -triose$ phosphate antiport system and, 724–725, 725f, 726f

in starch synthesis, 734, 735f

in sucrose synthesis, 734f

3-phosphoglycerate kinase, 721

phosphoglycerate kinase, 518–519, 726f

in glycolytic pathway, 513f, 521

phosphoglycerate mutase, 520

in glycolytic pathway, 513f, 520, 520f

phosphoglycerides. See glycerophospholipids

2-phosphoglycolate, 727

in glycolate pathway, 727–729, 728f

phosphoglycolohydroxamate, 203f

phosphohexose isomerase, 515

in gluconeogenesis, 515f

in glycolytic pathway, 513f, 515–516, 515f

phosphoinositide 3-kinase (PI3K), 435, 436f, 437f

phospholipase C (PLC), 425

in GPCR signaling, 425, 427f

membrane analysis using, 373f

phospholipases, 352, 352f

phospholipids, 346, 347f

biosynthesis of, 764–770

glycerophospholipids. See glycerophospholipids

lysosome degradation of, 352, 353b

membrane bilayer of, 367–368, 369f, 370f

of membrane proteins, 374, 375f

phosphodiester bonds of, 765f

sphingolipids. See sphingolipids

synthesis of

attachment of phospholipid head groups, 764–765, 764f

CDP-diacylglycerol in, 765–767, 766f, 768f

eukaryotic pathways to phosphatidylserine, phosphatidylethanolamine, and phosphatidylcholine, 767–768

plasmalogen, 768, 771f

precursors for, 760, 761f

sphingolipids, 770, 772f

transport to cellular membranes after, 770

transbilayer movement of, 378–379, 378f

phosphomannose isomerase, 522f

$4' -phosphopantetheine,$ 747

phosphopentose isomerase, 548

in pentose phosphate pathway, 547f, 549

phosphoprotein phosphatase 1 (PP1), 418, 567

as central regulator in glycogen metabolism, 568, 569f

glycogen phosphorylase regulation by, 217–218, 218f

glycogen synthase regulation by, 567, 567f, 568f

phosphoprotein phosphatase 2A (PP2A), 545, 546

phosphoprotein phosphatases, 217, 220

in β-adrenergic signaling termination, 417–418

phosphoproteins, 83t

phosphoramidite method, DNA synthesis using, 283, 284f

5-phosphoribosyl-1-pyrophosphate (PRPP), 806, 806s

histidine biosynthesis from, 814, 815f

purine biosynthesis from, 825–827, 825f, 826f

pyrimidine biosynthesis from, 827–829, 828f

5-phosphoribosylamine, 825, 826f

phosphorolysis, 558–559, 586f

of glycogen and starch, for glycolysis, 520, 522, 522f

phosphoryl group, 475–476, 476f, 484–485, 484f

glycolysis role of, 514

phosphoryl group transfers, 475–476, 476f

from 1,3-bisphosphoglycerate to ADP, 513f, 518–520

ATP and

in assembly of informational macromolecules, 485–487

energy provided by, 482–484, 483f

free-energy change for ATP hydrolysis, 479–481, 479f, 480t

in muscle contraction, 483, 487

phosphorylated compounds and thioesters with large free energies of hydrolysis, 481–482, 481f, 481t, 482f

reactions involved in, 484–485, 484f, 486b

in transphosphorylations between nucleotides, 487–488, 487f

from phosphoenolpyruvate to ADP, as last step in glycolysis, 513f, 521

phosphorylase b kinase, 427, 566

glycogen phosphorylase activation by, 565, 565f, 566f

phosphorylase kinase, glycogen phosphorylase regulation by, 218, 218f

phosphorylases, 477b

phosphorylated compounds

free-energy of hydrolysis of, 481–482, 481f, 481t, 482f

high-energy, 483f, 484

phosphorylation, 586f. See also photophosphorylation

of acetyl-CoA carboxylase, 753, 753f

β-adrenergic receptor desensitization by, 418–419, 419f

in bacteria signaling, 447f

CDK regulation by, 447, 448f, 449f

by CDKs, 449–450, 450f

in cyanobacteria, 718, 718f

in DNA replication, 918f

electron flow and, 716, 716f

of fructose 6-phosphate, 516

of glucose, 513f, 514–515

of glycogen synthase, 565–567, 567f, 568f

of HMG-CoA reductase, 782, 782f

of mannose residues, 1044f

in metabolic regulation, 501, 501f

of monosaccharides, 237

of nuclear transcription factors, 1084

nucleoside triphosphate synthesis via, 829

oxidation coupling to. See oxidative phosphorylation

of PDH complex, 593–594, 593f

by PKA

in β-adrenergic signaling, 413–416, 415f, 418f

in other GPCR signaling, 416b–417b, 420, 420t, 421f

by PKC, 425, 427f

by PKG, 422b–423b

posttranslational, 1036–1039, 1038f

of P-type ATPases, 392–394

of regulatory enzymes, 216–220, 217f, 218f

multiple, 218, 219f, 219t

respiration-linked, 520

RTK initiation of, 433f, 434–435, 434f

substrate-level, 520

in sucrose synthesis, 733f, 734

uncoupling of, 667t

phosphorylation potential $(Δ G_{p}),$ 479

calculation of, 480

phosphoserine, 77s, 1038f

phosphothreonine, 77s, 1038f

phosphotyrosine, 77s, 1038f

phosphotyrosine phosphatases, 442

phosphotyrosine-binding domains (PTB domains), 439, 439f

photochemical reaction center, 705, 706f

cyclic electron flow in, 713

cytochrome $b_{6} f$ complex, 712–713, 712f

determination of, 708

Fe-S, 708f, 711

oxygen-evolving complex in, 714–715, 715f

pheophytin-quinone, 708–710, 708f

photosystem I, 710–712, 711f

photosystem II, 710, 710f, 712f

in plants, 708–712, 709f

state transitions and distribution of, 713, 714f

types of, 707–708

photolithography, 322f

photolyases, DNA, 931t, 937–938, 937f

photon, 703

absorption of, 703

energy in, 703

photophosphorylation, 701

adenosine triphosphate synthesis by, 716, 716f

in cyanobacteria, 718, 718f

cyclic, 713

stoichiometry of, 716–717

photopigments, 704f, 705f

photorespiration, 727

in $C_{4}$ plants, 729–732, 729f

in CAM plants, 732

rubisco’s oxygenase activity in, 727

photosynthesis, 700–701

ATP synthesis by photophosphorylation, 716, 716f

$C_{2}$ cycle in, 721–722

in $C_{4}$ plants, 729–732, 729f

in CAM plants, 732

in chloroplasts, 701–704

${CO}_{2}$ assimilation in, 719, 720f

${CO}_{2}$ fixation, 720–721, 724f, 728f

light activation in, 720f, 725–726, 727f

NADPH and ATP requirements for, 722–724, 724f

3-phosphoglycerate conversion to glyceraldehyde 3-phosphate, 720f, 721–722

ribulose 1,5-bisphosphate regeneration, 720f, 722, 724f, 728f

stages of, 719–722, 720f

transport system for, 720f, 724–725, 725f

dark reactions of, 724

evolution of, 34, 717–718, 718f

in genetically engineered organisms, 729, 730b–731b

glycolate pathway in, 721–722, 725f, 727–729, 728f

light absorption, 701, 701f

by accessory pigments, 704f, 705

by chlorophylls, 704–705, 704f

by chloroplasts, 701–704, 702f, 703f

exciton transfer of, 705–707, 706f, 707f

oxygenic, 714

photochemical reaction center. See photochemical reaction center

photorespiration in. See photorespiration

products of, 719f

starch synthesis in, 733, 735f

sucrose synthesis in, 733–734, 733f

photosynthetic carbon-reduction cycle, 720f. See also Calvin cycle

photosynthetic processes, 34

photosystem I (PSI), 708, 709, 709f. See also Fe-S photochemical reaction center

in cyanobacteria, 717

cytochrome $b_{6} f$ complex and, 712–713, 712f

cyclic electron flow between, 713

excitation energy for, 713

LHCII and, 713, 714f

localization of, 714f

mechanism of, 710–712, 711f

state transition and, 713, 714f

structure of, 710–712, 711f

thylakoid membrane location of, 713

Z scheme of, 709f, 710

photosystem II (PSII), 707, 709, 709f. See also pheophytin-quinone reaction center

in cyanobacteria, 717

cytochrome $b_{6} f$ complex and, 712–713, 712f

excitation energy for, 713

LHCII and, 713, 714f

localization of, 714f

mechanism of, 710, 710f

oxygen-evolving complex and, 714–715, 715f

state transition and, 713, 714f

structure of, 710, 710f

thylakoid membrane location of, 713

Z scheme of, 709

photosystems, 705, 706f

phototrophs, 4f, 5

phycobilins

light absorption by, 704f

structure of, 704f

phycoerythrobilin, 704f

phylloquinone (QK), 711, 711f

phylogenetic tree, human, 329, 330f

phytanic acid, 617, 618f

α oxidation of, 618, 618f

$P_{i} .$ See inorganic orthophosphate

pI. See isoelectric point

PI3K. See phosphoinositide 3-kinase

PIC. See preinitiation complex

piericidin A, 666–667, 667t

pigments, lipids as, 360, 360f

pili, 5f

β-pinene, 356

Ping-Pong mechanism, 194–195, 194f, 195f

pioglitazone (Actos), 879t

${PIP}_{2} .$ See phosphatidylinositol 4,5-bisphosphate

${PIP}_{3} .$ See phosphatidylinositol 3

$P_{i} -triose$ phosphate antiport system, 724–725, 725f, 726f

PKA. See protein kinase A

$p K_{a},$ 57, 57f

of amino acids, 73t, 78–79, 78f, 79f, 80f

in Henderson-Hasselbalch equation, 60

of weak acids, 58–59, 58f, 59f

PKB. See protein kinase b

PKC. See protein kinase C

PKG. See protein kinase G

PKU. See phenylketonuria

Planck’s constant, 182

Planctomycetes, 798b–799b

plant cells

mitochondria of, NADH oxidation in, 685b

structure of, 6, 7f

plants

amino acid derivatives in, 820–821, 822f

$C_{3},$ 720, 732t

$C_{4},$ 729–732, 732t

CAM, 732, 732t

cellulose synthesis in, 736–738, 737f

${CO}_{2}$ assimilation in, 719, 720f

${CO}_{2}$ fixation, 720–721, 724f, 728f

light activation in, 720f, 725–726, 727f

NADPH and ATP requirements for, 722–724, 724f

3-phosphoglycerate conversion to glyceraldehyde 3-phosphate, 720f, 721–722

ribulose 1,5-bisphosphate regeneration, 720f, 722, 724f, 728f

stages of, 719–722, 720f

transport system for, 720f, 724–725, 725f

desaturases in, 754, 755f

eicosanoid synthesis in, 759

fatty acid synthesis in, 745, 750–751, 751f, 754–755, 755f

genetically engineered, 729, 730b–731b

gluconeogenesis in, 733f, 735–736, 736f

glycolate pathway in, 721–722, 725f, 727–729, 728f

metabolite pools in, 738–739, 738f

mitochondrial respiration in, 727

nitrogen-fixing bacteria symbionts of, 797, 801, 801f

osmotic pressure in, 52

photochemical reaction center in, 708–712, 709f

photorespiration in. See photorespiration

photosynthesis in. See photosynthesis

photosystem I, 710–712, 712f

photosystem II, 710, 710f, 712f

signaling in, 447f

plaques, atherosclerotic, 784, 784f

reverse cholesterol transport by HDL countering, 785, 785f

statin drugs and, 785, 786b–787b

plasma lipoproteins, 777

cholesterol transport as, 777–780, 778f, 778t, 779f, 779t

plasma membranes, 2, 2f

carbohydrate layer on, 247

composition and architecture of, 370f, 371f

amphitropic proteins, 372, 373f, 376

characteristic lipids and proteins, 367, 369f

fundamental properties, 369, 369f

integral membrane proteins, 372, 373f, 374f, 375f, 376f

lipid bilayer, 367–368, 369f, 370f

peripheral membrane proteins, 372, 373f, 375–377, 376f

dynamics of

catalysis of transbilayer lipid movements, 378–379, 378f

clustering of sphingolipids and cholesterol in rafts, 380–382, 380f, 381f

lateral diffusion of lipids and proteins in bilayer, 379–380, 379f, 380f

membrane curvature and fusion processes, 382–383, 383f, 384f

ordering of acyl groups in bilayer, 377–378, 377f

surface adhesion, signaling, and other processes of integral proteins, 383–384

fluid mosaic model of, 369, 369f

functions of, 367

glycolipids in, 253, 253f

glycophorin in, 374, 375f

glycoproteins on, 253

lectins on, 254–256, 255f, 256f

lipids in. See membrane lipids

lipopolysaccharides in, 253, 253f

proteins in. See membrane proteins

proteoglycans in, 247f, 248–251, 248f, 249f, 252f

rafts in

signaling protein segregation by, 440

sphingolipids and cholesterol in, 380–382, 380f, 381f

solute transport across

by ABC transporters, 395–396, 396f, 396t, 397b–398b

by active transport. See active transport

by aquaporins, 400–401, 400t

by chloride-bicarbonate exchanger, 389–392, 391f

by cotransport, 389–392, 391f, 398–399

by GLUT1, 387–389, 387f, 388f, 389f, 389t

by ion channels, 397b–398b, 401–402, 401f, 402f

ion gradients driving, 398–399, 400f

by $K^{+} channels,$ 402–403, 402f

in metabolic regulation, 499f

by passive transport. See passive transport

by P-type ATPases, 392–394, 393f, 394f

by secondary active transport, 398–399

transporter and ion channel structures and mechanisms for, 386–387, 387f

types of, 385–386, 385f

by V-type and F-type ATPases, 394–395, 395f

water movement across, 51f, 52–53, 52f

plasma proteins, 858, 858f

plasmalogens, 348, 349f, 768

synthesis of, 768, 771f

plasmids, 6, 305, 887, 888f

as cloning vectors, 305–306, 306f, 307f

plasmodesma, 7f

plasmodesmata, 729f, 730

Plasmodium falciparum, 256

plastocyanin, 709, 711

cyclic electron flow with, 713

plastoquinone $({PQ}_{A}),$ 359f, 360, 709f, 710

platelet-activating factor, 349, 349f, 768

synthesis of, 768, 771f

platelet-derived growth factor receptor (PDGFR), 437, 438f

platelets, 221, 858, 858f

in blood coagulation, 220f, 221

Plavix. See clopidogrel

PLC. See phospholipase C

pleckstrin homology (PH) domain, 440

plectonemic supercoiling, 897, 898f

PLP. See pyridoxal phosphate

pluripotent stem cells, 1090f, 1091, 1092

P/O ratio, 682

poisoning

botulinum toxin, 383

carbon monoxide, 158b–159b

cholera toxin, 424, 494

diphtheria toxin, 1040

methanol, 198

ricin, 1040

tetanus toxin, 383

by toxins acting on ion channels, 444–445

pol gene, 989, 989f

Pol I. See RNA polymerase I

Pol II. See RNA polymerase II

Pol III. See RNA polymerase III

Polanyi, Michael, 183

polar, uncharged R groups, 74f, 76, 76f

polar solutes

examples of, 46t

hydrogen bonding of, 45, 45f, 46f, 50, 50t

polarity, 73–74, 1087

of amino acids, 73–74

poly(A) site choice, 982, 983f

poly(A) tail, 980, 980f

polyacrylamide gel, 87–88, 87f, 88f, 89f

polyadenylate polymerase, 980

poly-ADP ribose polymerase 1 (PARP1), 948b–949b

polycistronic mRNA, 275, 276f

polyclonal antibodies, 167

polyketides, 360, 361f

polylinkers, 305f

polymerase chain reaction (PCR), 283

cloning adaptations of, 314–315, 315f

DNA amplification using, 283–286, 285f, 288b–289b

polymorphic proteins, 91

polynucleotide, 268

polynucleotide kinase, 303t

polynucleotide phosphorylase, 987, 1007

polynucleotides, 12–14

polyP. See inorganic polyphosphate

polypeptides, 81

folding process of, 131–132, 131f, 132f

mRNA coding for, 274–275, 276f

sequencing of, 91, 92f

classical-based methods for, 92–93, 92f, 92t, 93f

mass spectrometry methods for, 93–95, 94f, 95f

sizes and compositions of, 82–83, 82t, 83t

polysaccharides, 13, 229, 241–246

analysis of, 258–260, 259f

in feeder pathways for glycolysis

hydrolysis of, 522f, 523–525

phosphorolysis of, 522, 522f

hetero-, 241, 241f

in bacterial and algal cell walls, 244

glycosaminoglycans in ECM, 244–246, 246f

homo-, 241, 241f, 242

folding of, 243–244, 244f

fuel storage roles of, 242, 242f

structural roles of, 243, 243f, 244f

information carried by, 247, 254

lectin reading of, 254–256, 255f, 256f

lectin-carbohydrate interactions, 256–257, 257f, 258f

molecular weights of, 241

nomenclature of, 240, 240t

structures and roles of, 247t

polysomes, 1036, 1036f

polytopic integral membrane proteins, 372, 373f

polyunsaturated fatty acids (PUFAs), 343

β oxidation of, 611–612, 612f

in cardiovascular disease, 343

double bonds in, 342–343

eicosanoid synthesis from, 755, 758–759, 758f

nomenclature for, 343

synthesis of, 754, 754f, 755, 755f, 756b–757b, 758–759

polyuria, 400

POMC. See pro-opiomelanocortin

Popják, George, 775

porins, 374

porphobilinogen, 817, 818f

porphyrias, 817, 819b

porphyrin ring, 148, 148f, 149f

porphyrins, 817

degradation of, 817–819, 820f

glycine in biosynthesis of, 817–819, 817f, 819b

portal vein, 848f

Porter, Rodney, 165

positive regulation, 1057, 1058f

of eukaryotic promoters, 1077, 1078f

of galactose metabolism genes in yeast, 1081, 1081f, 1082t

of lac operon, 1066–1067, 1066f

positive supercoiling, 894, 894f

positive-inside rule, 375

positively charged R groups, 74f, 76

positron emission tomography (PET), tumor diagnosis using, 528b

posterior pituitary, 846f, 847f

postinsertion site, 917

posttranscriptional gene silencing, by RNA interference, 1085–1086, 1086f

posttranslational modifications

in protein targeting, 1041–1042, 1041f, 1042f

of proteins, 1015, 1016f, 1016t, 1036–1039

posttranslational modifications, 1037

of proteins, 1038f

PP1. See phosphoprotein phosphatase 1

PP2A. See phosphoprotein phosphatase 2A

PPAR (peroxisome proliferator-activated receptors), 616

in regulation of fatty acid oxidation, 616

PPARα, 616, 872, 872f, 873f

PPARβ, 872f, 873f

PPARδ, 872, 872f, 873f

PPARγ, 871–872, 872f, 873f

PPARs. See peroxisome proliferator-activated receptors

ppGpp, as regulatory molecule, 296

${PP}_{i} .$ See inorganic pyrophosphate

PPI. See peptide prolyl cis-trans isomerase

PPK-1. See polyphosphate kinase-1

PPK-2. See polyphosphate kinase-2

${PQ}_{A},$ 710

${PQ}_{b},$ 710

${PQ}_{b} H_{2},$ 710

Prader-Willi syndrome, 873

Pravachol. See pravastatin

pravastatin (Pravachol), 786b–787b

pRb. See retinoblastoma protein

prebiotic chemical reactions, 998–999, 999f

prebiotics, 874

precursor transcript, 972

prednisone, as steroid drug, 356, 356f

preinitiation complex (PIC), 969, 1080, 1080f

prenylation, 788

preparatory phase, of glycolysis, 511–513, 512f

cleavage of fructose 1,6-bisphosphate, 513f, 516, 517f

conversion of glucose 6-phosphate to fructose 6-phosphate, 513f, 515–516, 515f

interconversion of triose phosphates, 513f, 516–518, 518f

phosphorylation of fructose 6-phosphate to fructose 1,6-bisphosphate, 513f, 516

phosphorylation of glucose, 513f, 514–515

prephenate, in amino acid biosynthesis, 812

preproinsulin, 845f

pre-RCs. See pre-replicative complexes

pre-replicative complexes (pre-RCs), 928

preribosomal RNAs (pre-RNAs), 981

processing of, 983–984, 983f, 984f

pre-ribosomal RNAs (pre-rRNAs), 983

pre-RNAs. See preribosomal RNAs

presenilin-1, gene encoding, 331–333, 332f

pre-steady state, 188

pre-steady state kinetics, 188f, 196–197, 196f, 197f

of chymotrypsin, 204, 204f

PriA protein, 943

PriB protein, 943

PriC protein, 943

primaquine, 548b

primary active transport, 391, 391f

primary active transporters, 386

primary photopigments, 704f

primary structure, 90

of proteins, 90–91, 91f

amino acid sequence role in protein function, 91–92

biochemical information from amino acid sequences, 96, 98b

chemical synthesis of proteins, 95–96, 97f

classical-based methods for amino acid sequencing, 92–93, 92f, 92t, 93f

historical information from amino acid sequences, 96–100, 99f, 100f

mass spectrometry for amino acid sequencing, 93–95, 94f, 95f

proteins with determined amino acid sequences, 91–92, 92f

primary transcript, 972

formation and processing of, 972–973, 973f

of miRNAs, 986f

poly(A) tail addition to, 980, 980f

primase, 922, 923t, 924, 924f, 926t

primates, human genome comparisons with, 329–331, 330f

primer terminus, 917

primers, 283, 917

in DNA replication, 917, 918f, 922

in PCR, 285f, 286

priming, 567, 568f

pri-miRNA, 986f

primosome, replication restart, 943

prion diseases, protein misfolding in, 134b–135b

prion protein (PrP), 134b

Prism of Sennacherib, 28f

pristanic acid, 617

probiotics, 874

procarboxypeptidases A and B, 628

processivity, of DNA polymerases, 917

prochiral molecules, 588b

products, concentration of, determining actual free-energy changes from, 470–471

proenzymes, 220

profiling, DNA, 288b–289b

progesterone, 786, 786s

synthesis of, 785–787, 788f

programmed cell death, 455, 691. See also apoptosis

proinsulin, 845f

prokaryotes, 3

cells of, 5–6, 5f

proliferating cell nuclear antigen (PCNA), 929

proline, 74, 74s, 650, 806

biosynthesis of, 806, 807f, 808f

catabolism of, 640f, 650, 651f

properties and conventions associated with, 73t

proline-rich activation domain, 1082, 1082f

prolyl 4-hydroxylase, 119b

promoters, 963, 1056f

of Escherichia coli, 963–964, 966f, 969t

of Pol II, 1077–1080, 1079f, 1080f

positive regulation of eukaryotic, 1077, 1078f

RNA polymerase binding to DNA at, 1055–1056, 1055f

RNA polymerase II and, 968, 968f

transcription with, 970f, 971

RNA polymerase III and, 968

in transcription, 963–964, 964f, 966f

proofreading, 919

by aminoacyl-tRNA synthetases, 1020–1022

on ribosomes, 1034–1035

pro-opiomelanocortin (POMC), 845, 845f

prophase I in meiosis, 944f, 945f

propionate, 612, 874

β oxidation of, 612–613

Propionibacterium freudenreichii, 531

propionyl-CoA, 612

β oxidation of, 612–613, 613f

propionyl-CoA carboxylase, 612, 613, 613f

propranolol, 413s

proproteins, 220

prostaglandin $E_{2} ({PGE}_{2}),$ cAMP signaling by, 420

prostaglandin $H_{2}$ synthase, 755

inhibition of, 355, 355f, 758

in prostaglandin and thromboxane synthesis, 755, 758–759, 758f

prostaglandins (PG), 355, 355f, 755

synthesis of, 755, 758–759, 758f

prosthetic groups, 83, 83t, 179

posttranslational addition of, 1038

protease inhibitors, for HIV, 208–209, 208f, 209f

proteases, 92t, 93, 204

mechanisms of

chymotrypsin, 204–208, 204f, 205f, 206f–207f

treatments based on, 208–209, 208f, 209f

zymogens of, 220, 220f

proteasomes, 2, 448

in cyclin degradation, 448, 449f

in protein degradation, 1048–1049, 1049f, 1049t

protectins, 759

protein C, 222

protein circuits, 442

Protein Data Bank (PDB), 122b, 125, 127f, 363

protein disulfide isomerase (PDI), 133

protein factors

for DNA replication, 921–922

for RNA polymerase II, 968–971, 969t, 970f

protein families, 125

protein function, 71, 71f

catalysis. See enzymes

cellular, 317

DNA-based methods for studying, 317t

cellular proteomes, 319

CRISPR/Cas systems, 317t, 322–324, 323f

DNA libraries, 315–316, 316f, 320f

DNA microarrays, 322f

fusion proteins and immunofluorescence, 319–320, 319f, 320f

mass spectrometry, 319

protein-protein interaction studies, 320–322, 321f

RNA-Seq, 318–319, 318f

sequence or structural relationship studies, 316f, 317–318

transcriptomics, 318–319

ligand binding. See protein-ligand interactions

molecular, 317

movement, 169–172, 170f, 171f, 172f

phenotypic, 317

principles of, 147–148

protein kinase A (PKA), 413

FRET studies of, 416b–417b

in GPCR signaling

β-adrenergic system, 413–416, 415f, 418f

other regulatory molecules using, 416b–417b, 420, 420t, 421f

in triacylglycerol mobilization, 603, 604f

protein kinase B (PKB), 435, 436f

protein kinase C (PKC), 425, 437f

in GPCR signaling, 425, 427f

protein kinase G (PKG), 422b, 440

protein kinases, 217, 219f, 219t

allosteric activation of, 413, 415f

cell cycle regulation by, 446–447

oscillating CDK levels in, 447, 447f, 448f, 449f, 450f

protein phosphorylation in, 449–450, 450f

stages of, 446–447

consensus sequences for, 219, 219t

inhibition of, for cancer treatment, 452b–453b

oncogenes encoding, 451, 452b–453b

in plants, 446–447

Tyr. See receptor tyrosine kinases

protein phosphatases, 217

protein S, 222

protein synthesis, 1005, 1006f

fidelity in, 1036

five stages of

activation of amino acids, 1015, 1016f, 1016t, 1020–1023, 1020t, 1021f, 1023f, 1025b–1027b, 1029f

elongation, 1015, 1016f, 1016t, 1030–1035, 1031f, 1032f, 1034f

folding and posttranslational processing, 1015, 1016f, 1016t, 1036–1039, 1038f

initiation, 1015, 1016f, 1016t, 1028–1030, 1028f, 1029f, 1030f, 1031t

termination and ribosome recycling, 1015, 1016f, 1016t, 1035–1036, 1035f, 1036f

genetic code for

cracking of, 1007–1009, 1007f, 1008t, 1009f, 1010b–1011b, 1012t

expansion of, 1025b–1027b

mutation resistance of, 1012–1013

natural variations in, 1010b–1011b

reading of, 1013, 1013f, 1014f, 1015f

second, 1022–1023, 1029f

wobble in, 1010–1012, 1012f, 1012t

inhibition of, 1039–1040, 1039f

in liver, 850, 850f

by polysomes, 1036, 1036f

ribosome structure and function in, 1015–1018, 1018f

transcription coupling with, 1036, 1036f

translation, 1033b

tRNA structure and function in, 1018–1020, 1019f

protein targeting

in bacteria, 1045–1046, 1046f

endoplasmic reticulum posttranslational modification in, 1041–1042, 1041f, 1042f

glycosylation in, 1042–1045, 1043f, 1044f

of nuclear proteins, 1045, 1045f

receptor-mediated endocytosis in, 1046–1048, 1047f

protein tyrosine phosphatases (PTPs), 440, 442

protein-ligand interactions

chemical energy-modulated

myosin and actin, 170–171, 170f

sliding of filaments, 170–172, 172f

thin and thick filament organization, 169–172, 171f

complementary

analytical procedures based on, 167–168, 168f

antibody binding to antigens, 165–168, 166f, 168f

immune response cells and proteins, 164–165

graphical representation of, 150, 150f

induced fit and, 147

principles of, 147

reversible

cooperative, 155–160, 156f, 160f

globin family of oxygen-binding proteins, 149

heme binding of oxygen, 148–149, 148f, 149f

hemoglobin binding of carbon monoxide, 158b–159b

hemoglobin binding of oxygen, 155–156, 155f, 156f, 160f, 161–162, 162f

hemoglobin in sickle cell anemia, 162–164, 163f

hemoglobin subunit structure, 153–155, 153f, 154f

hemoglobin transport of carbon dioxide, 160–161, 160f

hemoglobin transport of hydrogen ions, 160–161, 160f

hemoglobin transport of oxygen, 153

mechanistic models for, 158–160, 160f

myoglobin binding of oxygen, 149, 149f

protein structure influence on, 152–153, 153f

quantitative description of, 150–152, 150f, 151t, 156–157, 160f

regulation of, 161–162, 162f

sites of, 147

protein-protein interaction domains, of regulatory proteins, 1063–1065, 1064f

proteins, 9f, 13, 18, 80

adaptor, 420

multivalent, 439–442, 439f, 441f

allosteric, 157

altered, 312–313, 312f

alternative splicing and, 981–983, 983f

amino acids in, 9f, 13, 72, 80–83, 82t, 83t

amplified production of

altered, 312–313, 312f

bacteria systems used for, 310, 310f

expression vectors for, 309, 310f

insect and insect virus systems used for, 311–312, 311f

mammalian cell systems used for, 312

tags for purification of, 313–314, 313t, 314f

yeast systems used for, 310–311

cellular concentration of, 1054, 1055f

characterization of, 87–89, 87f, 88f, 89f

chemical groups in, 83, 83t

chemical synthesis of, 95–96, 97f

degradation of

in liver, 850–851, 850f

in metabolic regulation, 499f, 499t

oxidation and urea production. See amino acid catabolism

specialized systems mediating, 1048–1049, 1048f, 1049t

denaturation of, 128–136, 129f

loss of function with, 129–130, 129f

renaturation after, 130, 130f

digestion of, 627–628, 628f

DNA encoding of, 29–30, 29f

as electron carriers, 492–494

enzymes as, 178–179. See also enzymes

folding of, 128–136, 129f

amino acid sequence role in, 130, 130f

assisted, 132–133, 132f

computational chemistry and, 138b–139b

defects in, 133–135, 133f, 134b–135b

as final step of synthesis, 1015, 1016f, 1016t, 1036–1039, 1037f

stepwise process of, 131–132, 131f, 132f

fusion, 313

for immunoprecipitation, 320–321, 321f

protein localization with, 319–320, 319f, 320f

for yeast two-hybrid analysis, 321–322, 322f

glycosylation of, 252–253, 252f

half-life of, 499t, 1049, 1049t

homologous, 99

in immune response, 164–165

localization of, 318–320, 318f, 319f, 320f

in membranes. See membrane proteins

modular, 409

molecular weight estimation of, 88, 88f

motor. See motor proteins

mRNA coding for, 274–275, 276f

naming conventions of, 914–915

oxygen-binding. See oxygen-binding proteins

pI of, determination of, 88, 89f

purification of, 84–87, 84f, 85f, 87t

immunoprecipitation, 320–321, 321f

tags for, 313–314, 313t, 314f

quantification of, 89–90, 90f

regulatory, 214

in development, 1087–1089, 1087f, 1088f, 1089f, 1090f

DNA-binding domains of, 1060–1063, 1060f, 1061f, 1062f, 1063f

protein-protein interaction domains of, 1063–1065, 1064f

ribosomal, 1070–1071, 1070f, 1071f

scaffold, 409, 439–442, 439f, 440f, 441f

separation of

column chromatography, 84–87, 84f, 85f, 87t

dialysis, 84

electrophoresis, 87–89, 87f, 88f, 89f

sequencing of, 91, 92f

classical-based methods for, 92–93, 92f, 92t, 93f

mass spectrometry methods for, 93–95, 94f, 95f

signaling

GPCRs. See G protein–coupled receptors

guanylyl cyclases, 422b–423b

multivalent adaptor, 439–442, 439f, 441f

nomenclature of, 411–412

RTKs. See receptor tyrosine kinases

segregation of, 442

types of, 411, 411f

sizes and compositions of, 82–83, 82t, 83t

structure of

comparisons of, 316f, 317–318

determination of, 136–137

layers of, 90–91, 91f

ligand binding and, 152–153, 153f

peptide bond effects on, 109–110, 110f

primary. See primary structure

quaternary. See quaternary structure

secondary. See secondary structure

tertiary. See tertiary structure

three-dimensional, 29–30, 29f, 107–111, 107f, 136–142

weak interactions stabilizing, 107–108

transcription initiation regulation by, 1056–1057, 1057f, 1058f

transcription regulation by, 966–967

undiscovered, 324–325

proteoglycan aggregates, 250, 252f

proteoglycans, 248

human diseases involving, 251b

structure and function of, 247–253, 247f, 248f, 249f, 252f

proteolytic cleavage, 214

of regulatory enzyme precursors, 220, 220f

in blood coagulation, 220–223, 220f

proteolytic processing, posttranslational, 1038

proteolytic systems, protein degradation by, 1048–1049, 1048f, 1049t

proteome, 13, 94, 317, 499

proteomics, 13, 317

proteostasis, 129, 129f, 1005

prothrombin, 359

protomers, 82, 127

proton gradient, 709f

ATP synthase, orientation of, 717f

in cytochrome $b_{6} f$ complex, 712f, 713

in electron flow and phosphorylation, 716, 716f

in oxidative phosphorylation, 659–660, 660f

active transport energized by, 683, 683f

ATP release driven by, 678, 678f

ATP synthesis driven by, 675–677, 675f, 676f, 677f

mitochondrial respiratory chain creation of, 672, 673f

rotary motion produced by, 681–683, 681f

proton hopping, in water, 54, 54f

proton pumps

oxygen-evolving complex as, 714–715, 715f

V-type and F-type ATPases, 394–395, 395f

proton-driven cotransporters, ABC transporter and, 396

proton-motive force, 673, 673f, 674

active transport energized by, 683, 683f

ATP synthesis driven by, 675–677, 675f, 676f, 677f

rotation of bacterial flagella by, 693, 693f

protons, transfer of, enzymatic catalysis of, 186, 187f

proto-oncogenes, 451

protoporphyrin, 148, 148f, 817, 818f

proximal His, 149

PrP. See prion protein

PRPP. See 5-phosphoribosyl-1-pyrophosphate

Prusiner, Stanley, 134b–135b

PS1 gene, localization of, 331–333, 332f

pseudouridine, 266s, 983f

PSI. See photosystem I

psicose, 233s

PSII. See photosystem II

PTB domains, 439, 439f. See also phosphotyrosine-binding domains

pTEFb protein, 969, 969t, 970f

PTEN, 437

PTPC. See permeability transition pore complex

PTPs. See protein tyrosine phosphatases

P-type ATPases, 392

phosphorylation of, 392–394, 393f, 394f

PUFAs. See polyunsaturated fatty acids

pulsed field gel electrophoresis, 309

Pumilio protein, 1088

pumps. See active transporters

purification

of proteins, 84–87, 84f, 85f, 87t

immunoprecipitation, 320–321, 321f

tags for, 313–314, 313t, 314f

purine bases, 264, 264f, 264s, 265t, 266f

biosynthesis of

de novo pathways, 825–827, 825f, 826f

regulation of, 826f, 827

salvage pathways, 835

conformations of, in DNA, 272–273, 272f, 273f

degradation of, uric acid produced by, 833–836, 834f, 835f

functional groups of, 268

Hoogsteen pairing of, 274, 275f

methylation of, 283

nonenzymatic transformations of, 280–283, 281f, 282f

nucleic acid structure and, 268, 269f

origin of, 998, 999f

puromycin, 1039, 1039f

purple bacteria, pheophytin-quinone reaction center of, 708–709, 708f

pyranoses, 234, 234f, 235

conformations of, 235, 236f

pyridine nucleotides, 493. See also nicotinamide adenine dinucleotide; nicotinamide adenine dinucleotide phosphate

pyridoxal phosphate (PLP), 629

in glycogen phosphorylase reaction, 558f

in serine and glycine metabolism, 644, 645f

in transfer of α-amino groups to α-ketoglutarate, 628–630, 629f, 630f

pyridoxine. See ${vitamin B}_{6}$

pyrimidine bases, 264, 264f, 264s, 265t, 266f

biosynthesis of

de novo pathways, 827–829, 828f

regulation of, 829, 829f

salvage pathways, 835

conformations of, in DNA, 272–273, 272f, 273f

degradation of, urea produced by, 833–835, 834f, 835f

functional groups of, 268

Hoogsteen pairing of, 274, 275f

methylation of, 283

nonenzymatic transformations of, 280–283, 281f, 282f

nucleic acid structure and, 268, 269f

origin of, 998, 999f

pyrimidine dimers, 281, 282f

photolyase repair of, 937–938, 937f

pyrophosphoryl groups, ATP donation of, 484–485, 484f

pyrosequencing, 292f

pyrrolysine, 76, 77s

in genetic code, 1025b

pyruvate, 521

acetyl-CoA from oxidation of, 574

allosteric and covalent regulation of, 593–594, 593f

oxidative decarboxylation reaction, 575, 576f

PDH complex coenzymes, 576, 576f, 577f

PDH complex enzymes, 576–577, 577f

PDH complex substrate channeling, 577–578, 578f

amino acid biosynthesis from, 809–811, 811f

amino acid degradation to, 640f, 644–647, 644f, 645f, 646t

fermentation of, 525

ethanol, 514, 525f, 529b, 530f, 532

foods and industrial chemicals produced by, 530–532

lactic acid, 514, 525f, 526, 529b

thiamine pyrophosphate in, 530, 531f, 532t

in gluconeogenesis, 545f

glucose synthesis from, 533, 534–537, 534f, 535f, 536f

from glycolysis, 510–511, 510f, 512f

energy remaining in, 514

fates of, 525–533, 525f

by phosphoryl group transfer from phosphoenolpyruvate to ADP, 513f, 521

oxidation of, 545f

PEP produced from, 481f, 534–537, 535f, 536f

regulation of, 544–545

pyruvate carboxylase, 534, 590

biotin in, 590–591, 592f

in gluconeogenesis, 534–537, 535f, 536f

in glyceroneogenesis, 762, 762f

oxaloacetate produced by, 590, 591f

pyruvate decarboxylase, 530

thiamine pyrophosphate in reactions of, 530, 531f, 532t

pyruvate dehydrogenase (PDH), 576, 577f

in hypoxic conditions, 687–688, 688f

in liver, 849, 850f

substrate channeling of, 577–578, 578f

pyruvate dehydrogenase (PDH) complex, 575

allosteric and covalent regulation of, 593–594, 593f

coenzymes of, 576, 576f, 577f

enzymes of, 576–577, 577f

oxidative decarboxylation reaction of, 575, 576f

substrate channeling in, 577–578, 578f

pyruvate dehydrogenase kinase, 593–594

pyruvate kinase, 521

ATP inhibition of, 544, 544f

in glycolytic pathway, 513f, 521

pyruvate phosphate dikinase, 729f, 730–731

Pythagoras, 548b

${PYY}_{3 - 36} .$ See peptide YY

Q

Q. See ubiquinone

Q. See mass-action ratio

Q cycle, 668, 669f, 712

QK. See phylloquinone

qPCR. See quantitative PCR

Q-SNAREs, 383, 384f

quantification, of proteins, 89–90, 91f

quantitative PCR (qPCR), 314–315, 315f

quantum, 703

quaternary structure, 90, 116

of hemoglobin, 153–155, 154f

of proteins, 90, 91f

range of, 126–128, 128f

quinolone antibiotics, 906b

quinones

lipid, as oxidation-reduction cofactors, 359–360

in reaction center, 708f, 709

R

R. See response coefficient

R groups, 71

amino acid, 71, 71f, 72, 73t

aromatic, 74f, 75–76, 75f

negatively charged, 74f, 76

nonpolar, aliphatic, 74–75, 74f

polar, uncharged, 74f, 76, 76f

positively charged, 74f, 76

R state, 155, 155f, 156f, 157

BPG effects on, 161–162, 162f

mechanistic models of, 158–160, 160f

RA. See retinoic acid

racemic mixture, 17

Racker, Efraim, 677

radicals, 472, 472f. See also free-radical reactions

DNA damage by, 283

in pheophytin-quinone reaction center, 708f, 710

Raf-1, in INSR signaling, 434f, 435

rafts, 380

membrane

signaling protein segregation by, 442

sphingolipids and cholesterol in, 380–382, 380f, 381f

RAG1 protein, 955

RAG2 protein, 955

Ramachandran, G. N., 115

Ramachandran plot, 110f, 115

of protein secondary structures, 115, 115f

Ramakrishnan, Venkatraman, 1017

Ran, 986f

Ran-GDP, 986f, 1046

Ran-GEF, 1045f, 1046

Ran-GTP, 1045f

Ransome, Joseph, 430b

Ras, 421, 423

in cancer, 423

as G-protein prototype, 421f

GTP hydrolysis and, 424f

in INSR signaling, 434–435, 434f

oncogenes encoding, 451, 452b–453b, 455

posttranslational isoprenylation of, 1038

rate constants, 182

activation energy relationship to, 182

denotation of, 150

$k_{cat} .$ See $k_{cat}$

rate equation, 182, 190

Michaelis-Menten, 191

rate of reaction. See reaction rates

rate-limiting step, 181

rational drug design, suicide inactivators in, 200, 201b–202b

RBP1, 968

RBP2, 968

RBP3, 968

RBP11, 968

reactants, concentration of, determining actual free-energy changes from, 470–471

reaction centers

in photosynthetic bacteria, 707–708

in vascular plants, 708–712, 709f

reaction coordinate diagram, 24, 180, 180f, 181f

for ATP synthase, 678–680, 678f

reaction intermediates, 181, 181f

reaction rates

entropy reduction and, 185–186, 186f

enzyme effects on

equilibria effects compared with, 180–182, 180f, 181f

study of. See enzyme kinetics

rate constants for, 182

activation energy relationship to, 182

denotation of, 150

thermodynamic definition of, 182, 182t

reactions. See chemical reactions

reactive oxygen species (ROS), 667f, 668

DNA damage by, 283

hypoxia leading to, adaptive responses for, 687–688, 688f

mitochondrial damage caused by, 688, 693–696

oxidative phosphorylation generation of, 668, 673–674, 674f

reading frames, 1007, 1007f

setting of, 1009

shifts in, 1013, 1013f, 1014f, 1015f

real-time PCR, 314–315, 315f

rearrangements, 474, 475f

standard free-energy changes of, 469t

RecA protein, 942–943, 942f, 943f

in induction of SOS response, 1068–1070, 1070f

RecBCD enzyme, 942–943, 942f, 943f

receptor enzymes, 411, 411f

receptor guanylyl cyclases, 422b–423b

receptor histidine kinase, in bacterial signaling, 447f

receptor potential, 431

receptor tyrosine kinases (RTKs), 433

inhibition of, for cancer treatment, 452b–453b

INSR

cross talk in signaling by, 438, 438f

phosphorylation cascade initiated by, 433f, 434–435, 434f

${PIP}_{3}$ role in signaling by, 435–437, 436f

receptor-ligand interactions

in cell cycle regulation, 446–447

apoptosis, 455–456, 456f

oncogenes in, 451, 452b–453b, 454

oscillating CDK levels in, 447, 447f, 448f, 449f, 450f

protein phosphorylation in, 449–450, 450f

tumor suppressor genes in, 454f, 455

of gated ion channels, 411, 411f

electrical signaling by, 442–443, 443f

neuronal action potentials produced by, 443–444, 444f

neurotransmitters interacting with, 444

toxins targeting, 444–445

GPCR. See G protein–coupled receptors

guanylyl cyclase, 422b–423b

hormonal. See hormones

membrane rafts involved in, 442

in microorganisms and plants, 447f

multivalent adaptor proteins involved in, 439–442, 439f, 441f

of nuclear receptors, 411, 411f

for hormones, 842–843, 843f

transcription regulation by, 445, 446f

RTK. See receptor tyrosine kinases

sensitivity of, 409, 410f

specificity of, 409, 410f

types of receptors involved in, 411, 411f

types of signals involved in, 410t, 411, 411t

receptor-mediated endocytosis, 781

of cholesteryl esters, 781–782, 781f

of proteins, 1046–1048, 1047f

recombinant DNA, 302

cloning vectors for

BACs, 307, 308f

expression, 309, 310f

plasmids, 305–306, 306f, 307f

YACs, 307–309

PCR adaptations for, 314–315, 315f

protein production using

altered genes and proteins, 312–313, 312f

bacteria systems used for, 310, 310f

expression vectors for, 309, 310f

insect and insect virus systems used for, 311–312, 311f

mammalian cell systems used for, 312

tags for purification of, 313–314, 313t, 314f

yeast systems used for, 310–311

restriction endonucleases and DNA ligases yielding, 302–304, 303f, 303t, 304t, 305f

recombinant DNA technology, 302. See also DNA cloning

recombinase, 950

recombination, gene regulation by, 1073, 1074f, 1074t

recombination signal sequences (RSSs), 954–955, 955f

recombinational DNA repair, 941, 941f, 942, 952f

red blood cells. See erythrocytes

${red}^{-}$ dichromats, 430b

red-anomalous trichromats, 430b

redox reactions. See oxidation-reduction reactions

reducing agents

disaccharides as, 240

monosaccharides as, 237, 238b–239b

reducing end, 237

reducing equivalent, 490, 662

reducing sugars, 237–241, 238b–239b

reduction, of double bonds for fatty acid synthesis, 748, 749f

reduction potential (E), 490–492, 491f

of biologically important half-reactions, 491t

of electron carriers in mitochondrial respiratory chain, 664–665, 664t

free-energy change calculation from, 491t, 492

reductive pentose phosphate pathway, 549–551, 549f, 550, 550f, 719, 722

Refsum disease, 618

regulated gene expression, 1054

regulators of G protein signaling (RGSs), 422

regulatory cascade, 220

in blood coagulation, 220–223, 220f

regulatory enzymes, 213

allosteric, 213

conformational changes of, 214–215, 214f, 215f

kinetic properties of, 215, 216f

covalent modification of, 216–217, 217f

in metabolic regulation, 500, 501f

multiple mechanisms used by, 223

phosphorylation of, 216–220, 217f, 218f, 219f, 219t

zymogens, 220, 220f

in blood coagulation, 220–223, 220f

regulatory nucleotides, 296, 296f

regulatory proteins, 214

in development, 1087–1089, 1087f, 1088f, 1089f, 1090f

DNA-binding domains of, 1060–1063, 1060f, 1061f, 1062f, 1063f

protein-protein interaction domains of, 1063–1065, 1064f

regulatory sequences, 886

regulon, 1067

relaxed DNA, 891, 893f

release factors, 1035, 1035f, 1036

Relenza. See zanamivir

renal cell carcinoma, 453b

renaturation, 130

DNA, 278–280, 279f, 280f

proteins, 130–131, 130f

repair, DNA, 29, 29f

replication, 884

DNA, 28–29, 29f

DNA supercoiling and, 891, 892f

replication factor C (RFC), 929

replication fork, 916, 916f, 924, 939f

in bacteria, 916, 916f, 924, 924f

in eukaryotes, 928–929

repair of, 941–943, 941f

replication protein A (RPA), 929

replication restart primosome, 943

replicative forms, 887

replicative transposition, 953, 953f

replicators, 928

replisome, 921, 926t

repolarization, of neurons, 443–444, 444f

reporter gene, 322

repressible genes, 1054

repression, 1054

catabolite, 1066–1067, 1066f

translational, 1084–1085, 1085f

repressors, 966, 1056, 1057, 1058f

in induction of SOS response, 1068–1070, 1070f

of lac operon, 1058

translational, 1070, 1070f

Reshef, Lea, 762

resolvins, 759

respirasomes, 671, 671f

respiration, 575f. See also cellular respiration

early views of, 465

respiration-linked phosphorylation, 520

respiratory chain, 661. See also mitochondrial respiratory chain

response elements, 498

in metabolic regulation, 498, 499f

response localization, 409

in signal transduction, 410f, 411

response regulator, in bacterial signaling, 447f

restriction endonucleases, 302–303

recombinant DNA from, 302–304, 303f, 303t, 304t, 305f

type II, 303t, 304t

restriction-modification system, 303

Retin-A. See tretinoin

retinal, 357, 358f

retinoblastoma protein (pRb), 450

cell cycle regulation by, 450, 450f

mutations in, 454

retinoic acid (RA), 357, 358f

retinoid hormones, nuclear receptor signaling by, 445, 446f

retinoid X receptors (RXRs), 783, 783f

retrohoming, 991f, 992, 995f

retrotransposons, 328, 990f, 991–993, 999

retroviruses, 208, 988, 999

cancer and AIDS caused by, 990–991, 990f, 991b

reverse transcriptases in, 988–990, 989f

transposon and intron similarities to, 990f, 991–993, 991f

reverse cholesterol transport, 781

by HDL, 780–781, 780f, 785, 785f

reverse transcriptase inhibitors, 991b

reverse transcriptase PCR (RT-PCR), 314

reverse transcriptases, 988, 989f

of HIV, 990, 991b

in recombinant DNA technology, 303t

telomerases as, 993, 994

reversible binding, protein-ligand interactions

cooperative, 155–160, 156f, 160f

globin family of oxygen-binding proteins, 149

heme binding of oxygen, 148–149, 148f, 149f

hemoglobin binding of carbon monoxide, 158b–159b

hemoglobin binding of oxygen, 155–156, 155f, 156f, 160f, 161–162, 162f

hemoglobin in sickle cell anemia, 162–164, 162f, 163f

hemoglobin subunit structure, 153–155, 153f, 154f

hemoglobin transport of carbon dioxide, 160–161, 160f

hemoglobin transport of hydrogen ions, 160–161, 160f

hemoglobin transport of oxygen, 153

mechanistic models for, 158–160, 160f

myoglobin binding of oxygen, 149, 149f

protein structure influence on, 152–153, 153f

quantitative description of, 150–152, 150f, 151t, 156–157, 160f

regulation of, 161–162, 162f

reversible inhibition, 197, 198–200, 200t

reversible terminator sequencing, 290, 291, 293f

Rezulin. See troglitazone

RFC. See replication factor C

RGSs. See regulators of G protein signaling

rhamnose, 236f, 237

Rheb, 871, 872f

rheumatoid arthritis, 356

rho utilization (rut), 967

Rhodobacter sphaeroides, 737f, 738

rhodopsin, 357, 429

in vision signaling, 429–431, 429f, 430b, 430f

rhodopsin kinase (RK), 429f, 431

Rhodospirillum rubrum, 721f

ρ-dependent terminators, 967, 967f

ρ-independent terminators, 967, 967f

RIA. See radioimmunoassay

ribofuranose, 265f

ribonuclease A, denaturation and renaturation of, 130–131, 130f

ribonucleases

$5'$ cap and, 973, 974f

messenger RNA degradation by, 986–988, 987f

residues, 123t

in ribosomal RNA processing, 984, 984f, 985f

ribonucleic acid (RNA), 13, 29f, 263

degradation of, 974

denaturation of, 278–280, 279f, 280f

elongation of, 969–971

in evolution, 31–33, 33f

gene regulation by, 1084–1086, 1086f

hydrolysis of, 267, 267f, 268f

intron splicing by, 975–976, 976f, 977f, 978f

lncRNAs, 1056, 1084, 1086

messenger. See messenger RNAs

miRNAs, 1085–1086, 1086f

nitrogenous bases. See nitrogenous bases

noncoding, 1086

phosphodiester linkages in, 267–268, 267f

processing of. See RNA processing

rate of turnover of, 974

ribosomal. See ribosomal RNAs

siRNAs, 1086, 1086f

small nuclear, 977

source of, 960–961

special function, 961

sRNAs, 1071–1073, 1072f

structure of

mRNAs, 274–275, 276f, 278f

nucleotide base effects on, 268, 269f

rRNAs, 276–277, 278f, 1015–1018, 1018f

single-stranded, 276, 276f

tRNAs, 276–277, 276f, 278f, 1018–1020, 1019f

synthesis of. See transcription

transcription initiation regulation by, 1056–1057, 1057f, 1058f

transfer. See transfer RNAs

types of, 263

ribonucleoproteins (RNPs), 960

ribonucleoside $2', 3' -cyclic monophosphates,$ 265, 268s

ribonucleoside 3′-monophosphates, 265, 268s

ribonucleotide reductase, 829, 830–832, 830f, 831f, 832f

ribonucleotides, 265, 265t, 266s

deoxyribonucleotide synthesis from, 829–832, 830f, 831f, 832f

ribose, 230s, 231, 233s

conformations of, 265f

in RNA, 264–265, 265f

ribose 5-phosphate

in Calvin cycle, 719, 724f

histidine biosynthesis from, 812–814, 815f

from pentose phosphate pathway, 547–548, 547f, 548b

ribose phosphate pyrophosphokinase, 806

ribosomal proteins (r-proteins), synthesis of, coordination of rRNA synthesis with, 1070–1071, 1070f, 1071f

ribosomal RNAs (rRNAs), 264, 960

processing of, 983–984, 983f, 984f, 985f

in bacteria, 983–984, 983f

in eukaryotes, 983–984, 984f, 985f

secondary structure, 996f

structure of, 276–277, 278f

synthesis of, 983, 983f

ribosome recycling, 1035f

ribosome recycling factor (RRF), 1036

ribosome rescue, 1033b, 1036f

ribosomes, 2, 5f, 7f

catalysis by, 999, 1017

discovery of, 1006, 1007f

mitochondrial, 692

pausing, arrest, and rescue, 1033b

proofreading on, 1034–1035

protein synthesis by. See protein synthesis

RNA and protein components, 1017t

structure of, 276–277, 276f, 278f, 999, 1015–1018, 1017f, 1018f

synthesis of, coordination of ribosomal protein synthesis with, 1070–1071, 1070f, 1072f

tRNA binding sites on, 1028–1029, 1028f

riboswitches, 1072, 1072f, 1074f

ribothymidine, 983f

ribozymes, 276, 277, 278f, 960, 972, 1000b. See also self-splicing introns

discovery of, 972, 995

hammerhead, 996, 998f

properties of, 996–997

ribosomes as, 999, 1017

self-sustained replication of, 999–1001, 1001f

ribulose, 233s

ribulose 1,5-bisphosphate, 719, 720

in Calvin cycle, 719–722, 721f, 724f

oxygen incorporation in, 724f, 727

regeneration from triose phosphates, 722, 723f, 724, 724f, 728f

ribulose 1,5-bisphosphate carboxylase/oxygenase (rubisco), 720. See also rubisco

activation of, 720, 723f

in $C_{3}$ plants, 720

in $C_{4}$ plants, 729–732, 729f

in CAM plants, 732

carboxylase activity of, 722f, 727

catalysis by

with ${CO}_{2}$ substrate, 720, 724f

with $O_{2}$ substrate, 724f, 727

evolution of, 720–721

genetically engineered, 729, 731b

magnesium in, 721, 724f

oxygenase activity of, 728f

in photorespiration, 724f, 727

structure of, 720, 721f

ribulose 5-phosphate

in Calvin cycle, 719, 723f, 728f

in pentose phosphate pathway, 547f, 548

ribulose 5-phosphate kinase, 723f

light activation of, 725, 727f

rice, β-carotene enrichment in, 358, 358f

Richardson, Jane, 123

ricin, 1040

rickets, 357, 357f

Rieske iron-sulfur proteins, 664

rifampicin, 971

Rinaldo, Piero, 653b

RISC protein complex, 986f

RK. See rhodopsin kinase

RNA. See ribonucleic acid

RNA (ribonucleic acid), 31

RNA editing, 1013

before translation, 1013–1015, 1013f, 1014f, 1015f

RNA interference (RNAi), 1086

posttranscriptional gene silencing by, 1085–1086, 1086f

RNA metabolism, RNA-dependent synthesis. See RNA-dependent synthesis

RNA polymerase, 82t

DNA-dependent, 961, 962f

as drug targets, 971–972

footprinting of, 965b

holoenzyme, 963, 963f

promoters and, 963

proofreading by, 963

regulation of, 966–967, 966f

by promoters, 1055–1056, 1055f

by proteins and RNAs, 1056–1057, 1057f, 1058f

structure of, 963, 963f

in transcription

in bacteria, 961–963, 962f, 963f, 966f

in eukaryotes, 967–968, 967f

initiation of, 961–962, 966f

RNA polymerase I (Pol I), 967–968

RNA polymerase II (Pol II), 967–968, 971f

$5'$ cap and, 973

function of, 968

promoters and, 968, 968f

promoters of, 1077–1080, 1079f, 1080f

protein factors for, 968–971, 969t, 970f

regulation of, 971

spliceosomal introns and, 978f, 980

subunits of, 968

transcription by, 968–971, 970f

RNA polymerase III (Pol III), 967–968

RNA processing, 972–973, 973f

alternative splicing, 981–983, 983f

exon transcription, 973

intron splicing, 975–976, 976f, 977f, 978f

mechanisms of, 975t

intron transcription, 973

of messenger RNAs

degradation rate of, 986–988, 987f

$5'$ cap of, 973, 974f

$3'$ end of, 980–981, 980f

polynucleotide phosphorylase, 987

primary transcripts, 972–973, 973f

of ribosomal RNA

in bacteria, 983–984, 983f

in eukaryotes, 983–984, 984f, 985f

ribozymes, 996f, 997–998, 998f

of special-function RNAs, 985–986, 986f

of transfer RNA, 985, 985f

RNA recognition motifs (RRMs), 1062, 1063f

RNA replicase. See RNA-dependent RNA polymerases

RNA splicing, 973

RNA synthesis, RNA-dependent, 990, 993–995, 995f, 1090f

RNA tumor viruses, 990, 990f

RNA world hypothesis, 31–33, 33f, 998

riboswitches as vestige of, 1073

RNA-dependent synthesis as clue to, 998–1001, 999f, 1000b, 1001f

RNA-coding genes, in human evolution, 331, 331f

RNA-dependent DNA polymerases. See reverse transcriptases

RNA-dependent RNA polymerases (RNA replicase), 994

RNA-dependent synthesis

as clue to RNA world, 998–1001, 999f, 1000b, 1001f

DNA, 990, 1090f

retroviruses in cancer and AIDS, 990–991, 990f, 991b

by reverse transcriptases, 988–990, 989f

similarity of transposons and introns to retroviruses, 990f, 991–993, 991f

telomerase as specialized reverse transcriptase, 993, 994

RNA, 990, 993–995, 995f, 1090f

RNA-DNA double helix, 961, 962f

RNAi. See RNA interference

RNase D, 985, 985f

RNase E, 987f

RNase P, 277f, 985, 985f

RNase Y, 987f

RNA-Seq, 318–319, 318f

Roberts, Richard, 975

rod cells, GPCR signaling in, 429, 429f

rofecoxib (Vioxx), 758

root nodules, nitrogen-fixing bacteria in, 797, 801, 801f

ROS. See reactive oxygen species

roscovatine, 453b

rosettes, in cellulose, 737f, 738

rosiglitazone (Avandia), 879t

Ross, Inman, 916

rotational catalysis, 680

of ATP synthesis, 680–682, 680f, 681f

proton flow driving, 681–683, 681f

rotenone, 666–667, 667t

Rous, F. Peyton, 990

Rous sarcoma virus, 990, 990f

Roux, César, 879

Roux-en-Y gastric bypass (RYGBP), 879

RPA. See replication protein A

rpoS gene, 1071–1073, 1071f

r-proteins. See ribosomal proteins

RRMs. See RNA recognition motifs

rRNAs. See ribosomal RNAs

RS system, 72

R-SNAREs, 383, 384f

RSSs. See recombination signal sequences

RTKs. See receptor tyrosine kinases

RT-PCR. See reverse transcriptase PCR

RTT106, 901

RU486. See mifepristone

rubisco, 720, 721f. See also ribulose 1,5-bisphosphate carboxylase/oxygenase

rubisco activase, 721, 723f

rut. See rho utilization

RuvAB, 943, 943f

RuvC, 943, 943f

RXRs. See retinoid X receptors

RYGBP. See Roux-en-Y gastric bypass

S

σ. See superhelical density

S. See entropy

S phase, 446, 447f

SAA. See serum amyloid A

Saccharomyces cerevisiae, 307

ethanol fermentation by, 530, 530f

introns in, 975

recombinant protein expression in, 310–311

Sagan, Dorion, 34

Salmonella typhimurium

lipopolysaccharides of, 253, 253f

regulation by genetic recombination in, 1073, 1074f, 1074t

salt bridge, protein structure and, 109

salvage pathways, 823

purine and pyrimidine base recycling via, 835

Sancar, Aziz, 937

Sanger, Frederick, 91, 92f, 286

Sanger sequencing, 286, 287–290, 287f, 290f

saquinavir, 209f

sarcomere, 170, 171f

sarcoplasmic reticulum, 170, 171f

sarcoplasmic/endoplasmic reticulum ${Ca}^{2 +}$ ATPase (SERCA pump), 393

structure and mechanism of, 393, 393f, 394f

satellite DNA, 890

saturated fatty acids

β oxidation of

acetyl-CoA oxidation in citric acid cycle, 609–611, 611t

four basic steps of, 607–608, 607f, 608f

hibernation fueled by, 610b

repetition of steps to yield acetyl-CoA and ATP, 608–609, 610b

structure and properties of, 342t, 343, 343f, 345f

synthesis of

acetyl group shuttling for, 751–752, 752f

in chloroplasts, 750–751, 751f

in cytosol, 750–751, 751f

desaturation after, 754–755, 755f, 756b–757b

fatty acid synthase active sites for, 747, 747f

fatty acid synthase reactions in, 745–747, 746f, 747f, 748–750, 749f, 750f

long-chain, 753, 754f

malonyl-CoA formation for, 744–745, 745f

palmitate, 747f, 748–750, 750f

regulation of, 752–753, 753f

repeating reaction sequence used in, 745–747, 746f, 747f, 748–750, 749f, 750f

SCAD. See short-chain acyl-CoA dehydrogenase

scaffold proteins, 409, 439–442, 439f, 440f, 441f

SCAP. See SREBP cleavage-activating protein

SCD. See stearoyl-ACP desaturase

Scheie syndrome, 251b

Schultz, Peter, 1025b

SCK test, 637b

SCOP2. See Structural Classification of Proteins database

scramblases, 378, 378f, 379

screenable marker, 306, 307, 308f

scRNA-Seq, 318

scurvy, 118b–119b

SDS. See sodium dodecyl sulfate

SecA, 1046, 1047f

SecB, 1045–1046, 1047f

second law of thermodynamics, 21, 22b

bioenergetics and, 466–467, 467t

second messengers, 296, 412

${Ca}^{2 +}$ , 425, 425t, 427f

space and time localization of, 425–428, 427f, 427t

cAMP

for β-adrenergic receptors, 412–413, 414f, 415f, 418f, 421

${Ca}^{2 +}$ crosstalk with, 428

other regulatory molecules using, 416b–417b, 420, 420t, 421f

removal of, 415f, 417

in triacylglycerol mobilization, 603, 604f

diacylglycerol, 425, 425t, 427f

${IP}_{3},$ 425, 425t, 427f

in metabolic regulation, 498

nucleotides as, 296

secondary active transport, 391, 391f

ion gradients providing energy for, 398–399, 400f

secondary active transporters, 386

secondary metabolites, 12, 360

biologically active lipids, 360, 361f

secondary photopigments, 704f

secondary structure, 90, 111–116

of proteins, 90, 91f, 108

α helix, 111–114, 112f, 112t, 113b, 374–375

β conformation, 112t, 114, 114f

β turns, 112t, 114, 115f

CD spectroscopy of, 116, 116f

dihedral angles of, 114–116, 115f

integral membrane, 374–375

second-order reaction, 150, 182

secretin, 628

SecYEG, 1046, 1047f

sedoheptulose 1,7-bisphosphatase, 723f, 725, 727f, 731b

sedoheptulose 7-phosphate

in Calvin cycle, 723f

in pentose phosphate pathway, 549, 549f, 550f

seed germination, gluconeogenesis in, 735–736, 736f

segment polarity genes, 1088

segmentation genes, 1088

selectable marker, 306, 307–309, 307f, 308f

selectins, 255, 255f, 256, 256f, 384

selenocysteine, 76, 77s

in genetic code, 1025b

SELEX. See systematic evolution of ligands by exponential enrichment

self-assembly, by living organisms, 1

self-experimentation, 56b

self-replication, by living organisms, 1

self-splicing introns, 975–976, 975t

enzymatic properties of, 996f, 997–998

secondary structure of, 996, 996f

semiconservative DNA replication, 915

senescence, telomere role in, 993

sensitivity, 409

separation

of lipids

adsorption chromatography, 361–362, 362f

gas chromatography, 362, 362f

of proteins

column chromatography, 84–87, 84f, 85f, 87t

dialysis, 84

electrophoresis, 87–89, 87f, 88f, 89f

septins, 382

sequence logos, 98b, 98f

sequence polymorphisms, 288b

in DNA genotyping, 288b–289b

sequencing

completed genomes, 35, 326–327, 327f

DNA

Sanger method for, 287–290, 287f, 290f

technologies for, 290–293, 292f, 293f

human genome

comparisons with closest biological relatives, 329–331, 330f

history of, 326–327, 327f

localization of disease genes in, 331–333, 332f

types of sequences seen in, 327–329, 327f

of human genome, evolutionary history learned from, 333–335, 334b–335b, 336f

protein, 91, 92f

classical-based methods for, 92–93, 92f, 92t, 93f

mass spectrometry methods for, 93–95, 94f, 95f

sequencing depth, 291

sequential feedback inhibition, 816, 827

sequential model, 159, 160, 160f

SERCA pump. See sarcoplasmic/endoplasmic reticulum ${Ca}^{2 +}$ ATPase

serine, 74s, 76, 644, 806

biosynthesis of, 806–809, 807f

catabolism of, 640f, 644–647, 644f, 645f, 646t

chymotrypsin acylation and deacylation of, 204–208, 204f, 205f, 206f–207f

in general acid-base catalysis, 187f

in glycolate pathway, 727–728, 728f

properties and conventions associated with, 73t

serine hydroxymethyltransferase, 644, 644f, 645f, 808

serine proteases, 205

serotonin, 822

biosynthesis of, 822, 823f

as neurotransmitter, 444

receptors for, 444

serum albumin, 603, 604f

serylglycyltyrosylalanylleucine, 81s

set point, body mass, 867, 867f

seven-transmembrane (7mt), 413

sex hormones

as cholesterol derivatives, 356, 356f

synthesis of, 785–787, 788f

sex lethal (Sxl) transcript, 981

SGOT test, 637b

SGPT test, 637b

sgRNA. See single guide RNA

SH2 domain, 435. See also Src homology domain

SH3 domain, 440

Shafrir, Eleazar, 762

Shaker family, voltage-gated $K^{+}$ channels of, 402–403

Sharp, Phillip, 975

shikimate, in amino acid biosynthesis, 811, 811f

Shimomura, Osamu, 319–320

Shine-Dalgarno sequence, 1028, 1028f, 1029, 1029f, 1030f

shivering thermogenesis, 856

Shoemaker, James, 653b

short interspersed elements (SINEs), 1014

short tandem repeat (STR), 288b, 328

in DNA genotyping, 288b–289b

in human genome, 328

short-chain acyl-CoA dehydrogenase (SCAD), 608

shuttle vectors, 309

sialic acids, 236f, 237. See also N-acetylneuraminic acid

sickle cell anemia, hemoglobin in, 162–164, 163f

sigmoid binding curve, for oxygen, 156f, 157

sigmoid saturation curve, of allosteric enzymes, 215, 216f

signal amplification, 843

signal recognition particle (SRP), 1042, 1042f

signal sequences, 1037, 1041, 1041f, 1042, 1042f

bacterial, 1045–1046, 1046f

for nuclear transport, 1045–1046, 1045f

removal of, 1037

signal transducers and activators of transcription (STATs), 869

signal transduction, 408

features of, 409–410, 410f

types of receptors involved in, 411, 411f

types of signals involved in, 410t, 411, 411t

signaling

in cell cycle regulation, 446

apoptosis, 455–456, 456f

oncogenes in, 451, 452b–453b, 454

oscillating CDK levels in, 447, 447f, 448f, 449f, 450f

protein phosphorylation in, 449–450, 450f

tumor suppressor genes in, 454f, 455

CO role in, 818

eukaryotic gene regulation by, 1083–1084, 1083f, 1084f, 1084t

gated ion channels involved in, 411, 411f

electrical signaling by, 442–443, 443f

neuronal action potentials produced by, 443–444, 444f

neurotransmitters interacting with, 444

toxins targeting, 444–445

GPCR. See G protein–coupled receptors

guanylyl cyclase, 422b–423b

hormonal. See hormones

integral membrane proteins involved in, 383–384

lipids involved in

eicosanoids, 355–356, 355f

hormones, 354

phosphatidylinositols and sphingosine derivatives, 354–355, 354f

steroid hormones, 356, 356f

vitamins A and D, 356–358, 357f, 358f

volatile compounds of vascular plants, 356

membrane rafts involved in, 442

in metabolic regulation, 498, 499f

in microorganisms and plants, 447f

multivalent adaptor proteins involved in, 439–442, 439f, 441f

by nuclear receptors, 411, 411f

for hormones, 842–843, 843f

transcription regulation by, 445, 446f

nucleotide roles in, 296

RTK. See receptor tyrosine kinases

signal transduction

features of, 409–410, 410f

types of receptors involved in, 411, 411f

types of signals involved in, 410t, 411, 411t

signature sequences, 100, 100f

SII protein, 969t, 970f

SIII protein, 969t, 970f

sildenafil (Viagra), 423b, 423s

silent mutations, 930, 1013

silk fibroin, structure and function of, 120, 121f

simple diffusion, 385, 385f

simple sequence repeats (SSRs), 328, 890

in human genome, 328

simple sugars. See monosaccharides

simple transposition, 952, 953f

simple-sequence DNA, 890

simvastatin (Zocor), 786b–787b

SINEs. See short interspersed elements

single cell RNA-Seq, 318

single guide RNA (sgRNA), 323, 323f, 324–325

single nucleotide polymorphisms (SNPs), 328

in human genome, 328, 329f

single particle tracking, lipid diffusion studies using, 379, 379f

single-molecule real-time (SMRT) sequencing, 290, 291, 293f

single-stranded DNA-binding protein (SSB), 923, 923t, 926t

siRNAs. See small interfering RNAs

sirtuins, 494

sister chromatids, 944–946, 945f, 947f

sitagliptin (Januvia), 879t

site-directed mutagenesis, 312, 312f

site-specific recombination, 940, 950–951, 951f, 952f. See also DNA recombination

size-exclusion chromatography, 86

of proteins, 84, 85f

skeletal muscle

ammonia transport from, 632–633, 632f

carbohydrate regulation in, 568–570, 569f, 570f

glucose uptake by, 389, 390b

hexokinase isozymes of, 539–541, 539f, 540b

metabolic functions of, 848f, 852–855, 854f, 855f, 856b–857b

motor proteins in

interactions of, 170–172, 172f

myosin and actin, 169, 171f

proteins organizing thin and thick filaments, 169–172, 171f

skin cancer, 932b

slow-twitch muscle, 853

Sly, William, 653b

small G proteins, 435

small interfering RNAs (siRNAs), 1086, 1086f

small intestine, fat absorption in, 602–603, 602f, 848f

small nuclear ribonucleoproteins (snRNPs), 977

small nuclear RNAs (snRNAs), 977, 985, 986

small nucleolar RNAs (snoRNAs), 984, 985, 985f, 986

small protein B (SmpB), 1033b, 1036f

small RNAs (sRNAs), mRNA regulation by, 1071–1073, 1072f

small temporal RNAs (stRNAs), 1085

SMC proteins, 908, 908f, 909f

SMN genes, 981b–982b

SmpB. See small protein B

SMRT sequencing. See single-molecule real-time sequencing

$S_{N} 2$ nucleophilic displacements, 475–476, 475f

in ATP reactions, 484–485, 486b

SNAP25, in vesicle fusion, 383, 384f

SNAREs, in vesicle fusion, 383, 384f

snoRNA-protein complexes (snoRNPs), 984, 985f

snoRNAs. See small nucleolar RNAs

snoRNPs, 984. See also snoRNA-protein complexes

SNPs. See single nucleotide polymorphisms

snRNAs. See small nuclear RNAs

snRNPs. See small nuclear ribonucleoproteins

sodium dodecyl sulfate (SDS), 87f, 88, 88f, 89f

solar energy, 700, 701f

solenoidal supercoiling, 898, 898f

solubility, of fatty acids, 342t, 343

solute transport across

by active transport. See active transport

by passive transport. See passive transport

solutes

amphipathic

examples of, 46t

water structure effects of, 48, 48f

charged, electrostatic interactions of, 46, 46t, 47f, 50t

colligative properties and, 51–53, 51f

membrane transport of

by ABC transporters, 395–396, 396f, 396t, 397b–398b

by active transport. See active transport

by aquaporins, 400–401, 400t

by chloride-bicarbonate exchanger, 389–392, 391f

by cotransport, 389–392, 391f, 398–399

by GLUT1, 387–389, 387f, 388f, 389f, 389t

by ion channels, 397b–398b, 401–402, 401f, 402f

ion gradients driving, 398–399, 400f

by $K^{+}$ channels, 402–403, 402f

in metabolic regulation, 499f

by passive transport. See passive transport

by P-type ATPases, 392–394, 393f, 394f

by secondary active transport, 398–399

transporter and ion channel structures and mechanisms for, 386–387, 387f

types of, 385–386, 385f

by V-type and F-type ATPases, 394–395, 395f

nonpolar

examples of, 46t

gases, 47, 47t

water structure effects of, 47–49, 48f, 49f, 50t

osmolarity of, 51–53, 51f

polar

examples of, 46t

hydrogen bonding in, 45, 45f, 46f, 50, 50t

solutions

aqueous. See aqueous solutions

osmolarity of, 51–53, 51f

solvation layer, 108

protein stability and, 108

solvent, water as. See aqueous solutions

solvents

colligative properties of, 51–53, 51f

for lipid extraction, 361, 362f

somatostatin

cAMP signaling by, 420

pancreatic secretion of, 860, 861f

sorafenib (Nexavar), 453b

sorbose, 233s

Sos, 434f, 435, 437f

SOS response, 939

induction of, 1068–1070, 1070f

Sp1, 1081–1083, 1082f

space-filling models, 15, 15f

specialized pro-resolving mediators (SPMs), 759

specific acid-base catalysis, 187

specific activity, 90

of enzymes, 89–90, 90f

specific hydrolysis, of lipids, 363

specific linking difference, 894

specificity, 185, 409

of enzymes, 182–183

binding energy contribution to, 185–186, 186f

of ion channels, 402–403, 402f

of lectin-carbohydrate interactions, 256–257, 257f, 258f

of signal transduction, 409, 410f

specificity constant, 193, 193t

specificity factors, 1056

spectrin, 380

spermidine, 822, 824f

spermine, 822, 824f

sphinganine, 768, 772f

sphingolipids, 350

as intracellular signal, 355

as membrane lipids, 371f

abnormal accumulations of, 353b

as derivatives of sphingosine, 350–351, 350f

lysosome degradation of, 35, 353b

rafts of, 380–382, 380f, 381f

as sites of biological recognition, 351

transbilayer movement of, 378, 378f

synthesis of, 768–770, 772f

sphingomyelin, 351f, 770

as intracellular signal, 355

synthesis of, 770, 772f

sphingomyelinase, defects in, 353b

sphingomyelins, 350, 350f

sphingosine, sphingolipids as derivatives of, 350–351, 350f

sphingosine derivatives, as intracellular signals, 354–355

spinal muscular atrophy (SMA), 981b–982b

spliceosomal introns, 977, 979f

mechanisms of, 975t, 977, 978f

requirements of, 977

spliceosome, 977, 978–980, 979f

mechanism of, 977, 978f

SPMs. See specialized pro-resolving mediators

spongiform encephalopathies, 134b–135b

sprinting, lactic acid fermentation during, 526, 529b

squalene, 774

four-ring steroid nucleus from, 774–775, 776f

isoprene condensation in formation of, 774, 775f

squalene 2,3-epoxide, 774, 776f

squalene monooxygenase, 774, 776f

SRA. See steroid receptor RNA activator

Src, autoinhibition of, 440, 440f

Src homology (SH2) domain, 433, 440

on Grb2, 434f, 435

on PI3K, 435, 436f

SREBP cleavage-activating protein (SCAP), 783, 783f

SREBPs. See sterol regulatory element-binding proteins

sRNAs. See small RNAs

SRP. See signal recognition particle

SSB. See single-stranded DNA-binding protein

SSRs. See simple sequence repeats

stability, 107

of α helix, 113–114

of proteins, 107–108

stability genes, mutations in, 454

Stahl, Franklin, 915

Stallings, Patricia, 653b

standard equilibrium constant $({K^{'}}_{eq})$ , 468

multiplicative nature of, 471

standard free-energy change relationship to, 182, 182t, 468–470, 468t, 469t

standard free-energy change $(Δ G^{\circ}),$ 24–25, 180, 468

additive nature of, 471

of ATP synthesis on surface of ATP synthase, 677–678, 678f

of electron transfer in mitochondrial respiratory chain, 672

in enzymatic reactions, 180, 180f

of fatty acyl-CoA formation, 485

of gluconeogenesis and glycolysis, 534, 535t

hydrolysis

ATP, 479–481, 479f, 480t

phosphorylated compounds and thioesters, 481–482, 481f, 481t, 482f

of metabolic enzymes, 502t

of oxidation-reduction reactions, 491t, 492

standard equilibrium constant relationship to, 182, 182t, 468–470, 468t, 469t

standard reduction potential $(E °),$ 490, 491f, 492, 709f

of biologically important half-reactions, 491t

of electron carriers in mitochondrial respiratory chain, 664–665, 664t

free-energy change calculation from, 491t, 492

standard transformed constants, 468

starch, 242

in amyloplasts, 701f

biosynthesis of, 733, 735f

chloroplast production of, 722

in feeder pathways for glycolysis

hydrolysis of, 522f, 523–525

phosphorolysis of, 522, 522f

folding of, 243–244, 244f

fuel storage in, 242, 242f

structures and roles of, 247t

starch granule, 7f

starch phosphorylase, 522, 522f

starch synthase, 733

starvation

fuel metabolism during, 863–864, 864t, 865f, 866f

ketone body production during, 620–621, 620f

triacylglycerol recycling during, 760, 761f, 762

state transition, 713

statins, 785, 786b–787b

STATs. See signal transducers and activators of transcription

steady state, 188, 188f

of bisubstrate reactions, 195f

of living organisms, 19–20, 497–498

maintenance of, 497–498

steady-state assumption, 190

steady-state kinetics, 188

stearate, 604f

synthesis of, 753, 754f

stearic acid, structure and properties of, 342t

stearoyl-ACP desaturase (SCD), 754, 755f, 756b

Steitz, Joan, 977

Steitz, Thomas A., 1017

stem cells, 1090, 1090f

control of, 1091f

stercobilin, 818, 820f

stereochemistry, 17, 18

stereoisomers, 14–18, 15, 17b, 17f, 19f

amino acids as, 71, 72–73, 72f

sugars as, 232, 232f

stereospecificity, 15, 18

of biomolecule interactions, 18, 19f

steric effects, homopolysaccharide folding and, 243–244, 244f

steroid drugs, 356, 356f

steroid hormones, 843f. See also specific hormones

as cholesterol derivatives, 356, 356f, 776, 777f, 785, 788f

cytochrome P-450 synthesis of, 690–691, 690f, 756b–757b

eukaryotic gene regulation by, 1083–1084, 1083f, 1084f, 1084t

nuclear receptor signaling by, 445, 446f

phosphoenolpyruvate carboxykinase regulation by, 763, 763f

signaling role of, 356, 356f

synthesis of, 785–787, 788f

steroid nucleus

of sterols, 352, 352f

synthesis of, 774–775, 776f

steroid receptor RNA activator (SRA), 1084

sterol regulatory element-binding proteins (SREBPs), 782–783, 783f

sterols, 346, 352. See also cholesterol

as membrane lipids, 368

fused carbon rings of, 352, 352f

lipid bilayer fluidity and, 378

rafts of, 380–382, 380f, 381f

transbilayer movement of, 378–379

stevioside, 231b

sticky ends, 304, 305f

stigmasterol, 352

synthesis of, 775, 776f

stimulatory G protein $(G_{s}),$ 413

in β-adrenergic signaling, 413, 415f, 416, 421

termination of, 417

other regulatory signals using, 420

stop codons. See termination codons

storage

of energy

in homopolysaccharides, 241–242, 242f

in triacylglycerols, 344–345, 344f

in waxes, 345–346, 346f

of genetic information, in DNA double helix, 270–272, 271f, 272f

storage lipids, fatty acids as, 347f

as hydrocarbon derivatives, 341–344, 342t, 343f

triacylglycerols, 344–345, 344f

waxes, 345–346, 346f

STR. See short tandem repeat

Streptomyces lividans, $K^{+} channels$ of, 402, 402f

streptomycin, 1040, 1040s

stress

AMPK metabolic coordination during, 870f, 871

cortisol signaling of, 865–866

stringent factor, 1071, 1071f

stringent response, 1071, 1071f

stRNAs. See small temporal RNAs

stroma, 701

stromal thylakoids, 702

Strong, Frank, 494

Structural Classification of Proteins database (SCOP2), 125–126, 127f

structural lipids, 346, 347f

galactolipids and sulfolipids, 349, 349f

glycerophospholipids

as derivatives of phosphatidic acid, 346–348, 347f, 348f

ether-linked fatty acids in, 349, 349f

lysosome degradation of, 352, 353b

sphingolipids as

abnormal accumulations of, 353b

as derivatives of sphingosine, 350–351, 350f

lysosome degradation of, 352, 353b

as sites of biological recognition, 351

sterols, 352, 352f

substitution mutation, 930

substrate channeling, 577

in citric acid cycle, 595, 595f, 596f

in PDH complex, 577–578, 578f

in urea cycle, 636

substrate specificity, 831

substrate-level phosphorylation, 520

substrates, 180

of enzymes, 180. See also enzyme-substrate complex

concentration effects of, 188–190, 189f, 191f, 215, 216f, 499f, 500f, 500t

reactions with two or more, 194–195, 194f, 195f

succinate, 584

in glyoxylate cycle, 736, 736f

as oncometabolite, 595

oxidation of, 579f, 586

succinyl-CoA conversion to, 579f, 584–586, 586f

succinate dehydrogenase, 586, 667

in citric acid cycle, 579f, 586

in mitochondrial respiratory chain, 665t, 666f, 667–668, 667f

mutations in, 595

succinic thiokinase, 584

in citric acid cycle, 579f, 584–586, 586f

succinyl-CoA, 582

amino acid conversion to, 640f, 650–651, 652f, 653b

as biosynthetic precursor, 590

conversion to succinate, 579f, 584–586, 586f

α-ketoglutarate oxidation to, 579f, 582–584, 583f, 587f

porphyrin biosynthesis from, 817f

succinyl-CoA synthetase, 584

in citric acid cycle, 579f, 584–586, 586f

sucrose, 229, 240, 240f, 733s

Calvin cycle and, 722

in germinating seeds, 735–736, 736f

movement of, 739f

in photosynthesis, 733–734, 733f

sweet taste of, 231b

synthesis of, 725, 733–734, 733f, 734f, 735f

sucrose 6-phosphate, 733, 733f

sucrose 6-phosphate phosphatase, 733, 733f

sucrose 6-phosphate synthase, 733, 733f, 734, 735f

sugar code, 254–257

lectin reading of, 254–256, 255f, 256f

lectin-carbohydrate interactions in, 256–257, 257f, 258f

sugar nucleotides, 560, 733

in glycogenesis, 560–563, 563f

sugars, 9f, 18, 229

disaccharides. See disaccharides

glucose. See glucose

liver metabolism of, 849–850, 849f

monosaccharides. See monoclonal antibodies

nucleotide, 733

reducing, 237–241

stereoisomerism of, 232, 232f

sweet taste of, 231b

suicide inactivators, 200, 201b–202b

sulfa antibiotics, 548b

sulfolipids, 349, 349f

sulfonylurea drugs, 861–862, 879t

Sumner, James, 178

sunitinib (Sutent), 453b

supercoiling, 891

DNA, 891, 891f, 892f

linking numbers describing, 893–895, 894f

plectonemic and solenoidal, 898, 898f

replication and transcription and, 891, 892f

topoisomerases changing, 895–898, 895f, 896f, 897f, 897t, 906b

underwinding of, 892–895, 893f, 894f, 895f

superfamilies, 126

superhelical density (σ), 894

superoxide dismutase, 283, 674

superoxide radical, 668

mitochondrial respiratory chain production of, 668, 673–674, 674f

supersecondary structure, of globular proteins, 123f

supramolecular structures, 8–9

of cells, 8–9, 9f

ribosomes as, 1015–1018, 1018f

surface adhesion, integral membrane proteins involved in, 383–384

Sutent. See sunitinib

Sutherland, Jr., Earl W., 562b, 565–566

sweetness, of sugars, 231b

SWI/SNF family, 1075, 1076f

switch I, 421, 424f

of G proteins, 421

switch II, 421, 424f

of G proteins, 421

symbionts, 797

gut microbials on, 874–875, 875f

nitrogen-fixing bacteria, 797, 801, 801f

symport, 391, 391f

ion gradients providing energy for, 398–399, 400f

synapses, membrane fusion at, 383, 384f

syndecans, 248, 248f, 249

Synechococcus elongatus, 710f, 711f

synteny, 318, 318f

synthases, 477b

synthesis, chemical. See chemical synthesis

synthetases, 477b

α-synuclein, 135

system, 20

systematic evolution of ligands by exponential enrichment (SELEX), 999, 1000b

systems biology, 27, 301

Szent-Györgyi, Albert, 119b

T

T. See thymine

T cells, 165

T loops, 993

in telomeres, 993, 994

T lymphocytes, 165

T state, 155, 155f, 156f, 157

BPG effects on, 161–162, 162f

mechanistic models of, 158–160, 160f

T1 transporter, 560, 560f

$T_{3} .$ See triiodothyronine

$T_{4} .$ See thyroxine

T7 promoter, recombinant protein expression using, 310, 310f

tadalafil (Cialis), 423b, 423s

Tagamet. See cimetidine

tagatose, 233s

tags, 313

epitope, 320

for immunoprecipitation, 320–321, 321f

terminal, 313, 313t, 314f

talose, 233s

Tamiflu. See oseltamivir

tamoxifen, 445, 445s

tandem affinity purification (TAP) tags, 321, 321f

tandem MS (MS/MS), 94, 95, 95f

Tangier disease, 785, 785f

TAP tags. See tandem affinity purification tags

Taq polymerase, 285, 285f

Tarceva. See erlotinib

targeting, protein

in bacteria, 1045–1046, 1047f

endoplasmic reticulum posttranslational modification in, 1041–1042, 1041f, 1042f

glycosylation in, 1042–1045, 1043f, 1044f

of nuclear proteins, 1045–1046, 1045f

receptor-mediated endocytosis in, 1046–1048, 1047f

tastes

detection of, GPCR signaling in, 431

sweet, 231b

TATA box, 968, 968f, 1078, 1079f, 1080f

TATAAT sequence, 963, 964f

TATA-binding protein (TBP), 968–969, 970f, 1080, 1080f

Tatum, Edward, 886

tau protein, 135

taurocholic acid, 352s

tautomerization, 481f

tautomers, 268

Tay-Sachs disease, 353b

TBP. See TATA-binding protein

TBP protein, 969, 969t, 970f

$T_{C}$ cells. See cytotoxic T cells

TCA cycle. See tricarboxylic acid cycle

T-cell receptors, 165

telomerase, 993

as specialized reverse transcriptase, 993, 994

telomeres, 890, 890f, 890t, 891, 993, 994

Temin, Howard, 988, 989

temperature

lipid bilayer composition variation with, 377f, 378

units of, 467t

template, 915

template strand, 915, 962

for DNA replication, 915, 917, 918f

for transcription, 962, 962f

Ter sequence, 927, 927f

terminal sequences, 967, 967f

terminal tags, for protein purification, 313–314, 313t, 314f

terminal transferase, 303t

termination, 1035

of β-adrenergic receptor signaling, 416–418

of DNA replication, 926–927, 927f

of DNA-dependent transcription, 967, 967f

of protein synthesis, 1015, 1016f, 1016t, 1035–1036, 1035f

ribosome rescue and, 1033b, 1036f

termination codons, 1009, 1009f

protein synthesis termination by, 1035–1036, 1035f

variations in, 1010b–1011b

termination factors, 1035, 1035f

terminators, of E. coli, 967, 967f

ternary complex, 194–195, 194f, 195f

teromerase, 141f

territories, chromosome, 908f

tertiary structure, 90, 116

amino acid sequence and, 130–131, 130f

of proteins, 90, 91f, 108, 136–142

classification based on, 125–126, 127f

fibrous, 116–120, 117f, 117t, 119b, 119f, 120f, 121f

globular, 120–124, 121f, 122f, 123f, 124f, 125f

intrinsically disordered, 125, 126f

tertrahydrobiopterin, 649f

testosterone, as cholesterol derivative, 356f

tetanus toxin, 383

tetany, 56b

tetracyclines, 1040, 1040s

tetrahydrobiopterin, 644

in phenylalanine catabolism, 649f, 650

tetrahydrocannabinol (THC), 874f

tetrahydrofolate $(H_{4} folate),$ 641

in amino acid degradation, 641–644, 641f, 642f

in serine and glycine metabolism, 644, 645f

in thymidylate synthesis, 833, 833f

Tetrahymena thermophila, 976, 996, 996f, 997f

tetrasaccharide bridge, of proteoglycans, 248, 248f

tetrodotoxin, 444

tetrose erythrose 4-phosphate, 549

tetroses, 231

tezacaftor, 398b

TF. See tissue factor

TFIIA protein, 969, 969t, 970f

TFIIB protein, 969, 969t, 970f

TFIID protein, 969, 969t, 970f

TFIIE protein, 969, 969t, 970f

TFIIF protein, 969, 969t, 970f

TFIIH protein, 969, 969t, 970f

TFIIS protein, 969t, 970f

TFP. See trifunctional protein

TFPI. See tissue factor protein inhibitor

TH cells. See helper T cells

THC. See tetrahydrocannabinol

theozymes, 138b

thermodynamic constants, 24

thermodynamic effect, of ATP concentrations, 503

thermodynamics, 19–27, 20f, 22b–23b

bioenergetics and

additive nature of free-energy changes, 471

first and second law of thermodynamics, 466–467, 467t

free energy sources of cells, 467

reactant and product concentration effects on actual free-energy changes, 470–471

relationship between standard free-energy change and equilibrium constant, 182, 182t, 468–470, 468t, 469t

of enzymes catalysis, 181–182, 470–471

first law of, 20

physical constants and units used in, 467t

of protein folding, 131–132, 132f

second law of, 21, 22b

thermogenesis, 852

in brown adipose tissue, 690, 690f, 851f, 852, 853f

mitochondrial, 689, 690f

plant, 685b

shivering, 855

thermogenin. See uncoupling protein 1

Thermosynechococcus vulcanus, 710f

thiamine. See ${vitamin B}_{1}$

thiamine pyrophosphate (TPP), 530

in fermentation reactions, 530, 531f, 532t

in PDH complex, 576

in transketolase reaction, 549, 550f

thiazolidinediones, 763–764, 879t

glyceroneogenesis effects of, 763–764

thick filaments, 169, 170–172, 170f

actin thin filament interactions with, 170–172, 172f

organization of, 169–172, 171f

thin filaments, 169, 170–172, 170f

myosin thick filament interactions with, 170–172, 172f

organization of, 169–172, 171f

thin-layer chromatography (TLC), of lipids, 362, 362f

thioesterase, 750

thioesters, 482, 575

free-energy of hydrolysis of, 481–482, 481f, 481t, 482f, 483f

thiolase, 608

in fatty acid oxidation, 607f, 608

in ketone body formation, 619–620, 619f

thiols, as activating leaving groups, 476

thiolysis, 607f, 608

thiophorase. See β-ketoacyl-CoA transferase

thioredoxin, 723f, 725, 727f, 829

in deoxyribonucleotide synthesis, 830, 830f

thioredoxin reductase, 830, 830f

4-thiouridine, 266s, 983f

Thomson, James, 1091

$3'$ end, 267, 267f

of messenger RNAs, 980–981, 980f

$3'\to 5'$ exonuclease activity, in DNA polymerases, 917–919

three-dimensional structure

of biomolecules, 14–18, 15f, 16f, 18f, 19f

of integral membrane proteins, 374

of nucleic acids

DNA double helix, 270–272, 271f, 272f

DNA variation in, 272–273, 272f, 273f

mRNAs, 274–275, 276f, 278f

nucleotide base effects on, 268, 269f

rRNAs, 276–277, 278f, 1018–1020, 1018f

tRNAs, 276–277, 276f, 278f, 1018–1020, 1019f

unusual structures adopted by DNA sequences, 273–274, 273f, 274f, 275f

of proteins, 29–30, 29f, 107, 107f

determination of, 136–142

threonine, 74s, 76, 646, 647, 650–651, 810

biosynthesis of, 811f

catabolism of, 640, 640f, 644–647, 644f, 646t, 647f, 650–651, 652f, 653b

properties and conventions associated with, 73t

threose, 233s

thrombin, 221

in blood coagulation, 221

heparan sulfate and, 249–250, 249f

thrombomodulin, 222

thromboxane synthase, 758, 758f

thromboxanes (TX), 221, 355, 355f, 356, 758

synthesis of, 755, 758–759, 758f

Thudichum, Johann, 351

thylakoid membranes, 709

galactolipids in, 349, 349f

light-induced transport across, 720f, 725

photosystems in, 706f, 709f, 714f

PSI and PSII localization in, 713, 714f

thylakoids, 7f, 701

thymidylate (TMP), 265t, 837f

biosynthesis of, 833, 833f

degradation of, 833–835, 834f, 835f

thymidylate synthase, 833, 833f, 837f

inhibition of, 836, 836f

thymine (T), 264, 264s, 265t

base pairing of, 269f

degradation of, 833–835, 834f, 835f

in DNA, evolutionary reasons for, 280

methylation of, 283

thyroid hormones, 843f

nuclear receptor signaling by, 445, 446f

thyrotropin, lectin recognition of, 254

thyrotropin-releasing hormone (TRH), 844s

cells responding to, 409

structure of, 844f

time of flight (TOF), 94

tissue factor (TF), 222

tissue factor protein inhibitor (TFPI), 222

tissues

buffers in, 60f, 61–63, 62f, 63f

damage to, liver enzyme assays for, 637b

fractionation of, 8f

specific metabolic functions of, 848, 848f

adipose tissues, 851–852, 851f, 853f

blood, 857–859, 858f

brain, 855–857, 855f

liver, 848–851, 849f, 850f, 851f

muscle, 852–855, 854f, 855f, 856b–857b

titin, 82, 82t

titration curves, 58, 58f, 59f

of amino acids, 78–79, 78f, 79f, 80f

TLC. See thin-layer chromatography

TLS polymerases, 940

TMP. See thymidylate

tmRNA. See transfer-messenger RNA

TNF. See tumor necrosis factor

tocopherols, 359

as oxidation-reduction cofactor, 359–360

tolbutamide, 862f

top-down signaling, hormonal, 845–846, 846f, 847f

topoisomerases, 895, 922

in chromatin, 901

DNA, 895–898, 895f, 896f, 897f, 897t, 906b

in DNA replication, 922–923, 923t

inhibition of, 906b

in replication termination, 928f

topoisomers, 894

topologically associating domains (TADs), 903, 903f

topology, 891

of GLUT1, 388f

of integral membrane proteins, 374–375, 374f

amino acid sequence prediction of, 374, 375f, 376f

of supercoiled DNA, 891

topology diagram, 125, 127f

topotecan (Hycamtin), 906b

torpor, 610b

totipotent stem cells, 1090, 1090f

toxic shock syndrome, 253

toxins

ammonia, 633

botulinum, 383

cholera, 424, 494

ion channels targeted by, 444–445

protein synthesis inhibition by, 1039–1040, 1039f

tetanus, 383

TPP. See thiamine pyrophosphate

tracrRNA, 323, 323f

TRADD, in apoptosis, 455, 456f

trans fatty acids, 342

harmful health effects of, 345

trans-activating CRISPR RNA, 323, 323f

transaldolase, 549

in pentose phosphate pathway, 549–551, 549f, 550f, 551f

transaminases, 628

in transfer of α-amino groups to α-ketoglutarate, 628–630, 629f, 630f

transamination reactions, 628

in amino acid metabolism, 628–630, 629f, 630f

transcription, 275, 884, 960

DNA replication compared with, 961

DNA supercoiling and, 891, 892f

DNA-dependent

nuclear RNA polymerases in, 967–968, 968t

promoters in, 963–964, 964f, 966f

protein factors for, 968–971, 969t, 970f

regulation of, 966–967, 966f

RNA polymerases in, 961–963, 962f, 963f

selective inhibition in, 971f

termination of, 967, 967f

elongation of, 964, 966f

error rate of, 963

initiation of, 963–964, 966f

primary transcript, 972

regulation of. See gene regulation

regulatory sequences for, 962, 962f

by RNA polymerase II, 968–971, 970f

template strand for, 962, 962f

translation coupling with, 1036, 1036f

transcription activators, 1078

DNA-binding, in transcription factor assembly, 1078–1079, 1079f, 1080f

modular structure of, 1081–1083, 1082f

transcription attenuation, 1068

of genes for amino acid biosynthetic enzymes, 1067–1068, 1067f, 1069f

transcription factors, 498, 968

DNA-binding activators and coactivators in assembly of, 1077–1080, 1079f, 1080f

in glycolysis and gluconeogenesis regulation, 545–546, 545t, 546f

in metabolic regulation, 498, 499f

phosphorylation of, 1084

in RNA polymerase II transcription, 970f, 971f

transcriptional activation, 1080, 1080f

transcriptional regulation

of fatty acid oxidation, 616

of glycolysis and gluconeogenesis, overall changes in, 545–546, 545t, 546f

of HMG-CoA reductase, 782f, 783, 783f

transcriptome, 317, 499, 960

transcriptomics, 317, 318–319

transdeamination, 631

transducin, in vision signaling, 429f, 430–431, 430b, 430f

transduction, signals. See signal transduction

transesterification reaction, 975, 976f, 997, 997f

transfection, 312

transfer RNAs (tRNAs), 264, 960

amino acid activation by, 1015

amino acid attachment to, 1020–1023, 1020t, 1021f, 1023f, 1025b–1027b

aminoacyl-tRNA synthetase interactions with, 1022–1023, 1023f, 1029f

anticodons on. See anticodons

codon binding to, 1008, 1008t

codon recognition by, 1010–1012, 1012f, 1012t

discovery of, 1006, 1007f

genetic code expansion and, 1025b–1027b

primary transcript for, 973

processing of, 985, 985f

ribosomal binding sites for, 1028–1029, 1028f

RNA polymerase III synthesis of, 968

structure of, 276–277, 276f, 278f, 1018–1020, 1019f

synthesis of, 983–985, 983f

transferases, 179t

transfer-messenger RNA (tmRNA), 1033b, 1036f

transferrin, 584b

transferrin receptor, 584b

transformation, 306

transformylase, 1024

transition mutation, 1013

transition state, 25, 26, 26f, 180, 180f

in enzymatic reactions, 180, 181f

weak interaction optimization in, 183–186, 183f, 184f, 185f

transition-state analogs, 200, 202, 203f

protease inhibitors as, 209, 209f

vanadate as, 392

transketolase, 549

in Calvin cycle, 723f

defects in, 551

in pentose phosphate pathway, 549–551, 549f, 550f, 551f

translation, 884, 1006. See also protein synthesis

translational frameshifting, 1013, 1013f, 1014f, 1015f

translational repression, of mRNAs, 1084–1085, 1085f

translational repressor, 1070, 1070f

translocase, 179t, 1032

translocation, 1032, 1034, 1034f

transpeptidase, antibiotic inhibition of, 211, 212f, 213f

transphosphorylations, between nucleotides, ATP energy for, 487–488, 487f

transport

active, 385f, 386

against concentration or electrochemical gradient, 391–392, 391f

ion gradients providing energy for, 398–399, 400f

proton-motive force driving, 683, 683f

of ammonia

by alanine, 632–633, 632f

by glutamine, 631–632, 632f

of cholesterol

by HDL, 778f, 778t, 779f, 779t, 780–781, 780f, 785, 785f

by plasma lipoproteins, 777–780, 778f, 778t, 779f, 779t

by receptor-mediated endocytosis, 781–782, 781f

regulation of, 782–784, 782f, 783f, 785f, 786b–787b

of ${CO}_{2}$ , 160–161, 160f

of fatty acids into mitochondria, 603–606, 605f, 606f

hydrogen ion, 160–161, 160f

oxygen, 153

passive, 385, 385f

of proteins

in bacteria, 1045–1046, 1047f

endoplasmic reticulum posttranslational modification for, 1041–1042, 1041f, 1042f

glycosylation for, 1042–1045, 1043f, 1044f

to nucleus, 1045–1046, 1045f

receptor-mediated endocytosis in, 1046–1048, 1047f

of solutes across membranes

by ABC transporters, 395–396, 396f, 396t, 397b–398b

by active transport. See active transport

by aquaporins, 400–401, 400t

by chloride-bicarbonate exchanger, 389–392, 391f

by cotransport, 389–392, 391f, 398–399

by GLUT1, 387–389, 387f, 388f, 389f, 389t

by ion channels, 397b–398b, 401–402, 401f, 402f

ion gradients driving, 398–399, 400f

by $K^{+}$ channels, 402–403, 402f

in metabolic regulation, 499f

by passive transport. See passive transport

by P-type ATPases, 392–394, 393f, 394f

by secondary active transport, 398–399

transporter and ion channel structures and mechanisms for, 386–387, 387f

types of, 385–386, 385f

by V-type and F-type ATPases, 394–395, 395f

transporters. See also specific transporters

active, 386

ABC transporters, 395–396, 396f, 396t, 397b–398b

P-type ATPases, 392–394, 393f, 394f

V-type and F-type ATPases, 394–395, 395f

in metabolic regulation, 499f

passive, 385

chloride-bicarbonate exchanger, 389–392, 391f

GLUT1, 387–389, 387f, 388f, 389f, 389t

structure and mechanism of, 386–387, 387f

transposition, 940, 952

in bacteria, 951–953, 953f

direct, 952–953, 953f

in eukaryotes, 953

replicative, 953, 953f

simple, 952, 953f

transposons, 325b, 328, 951

bacterial, 952

complex, 952

eukaryotic, 953

in human genome, 328

recombination of, 951–953, 953f

retrovirus similarities to, 990f, 991–993, 991f

from RNA world, 999

trans-translation, 1033b

trans- $Δ^{2}$ -enoyl-CoA, 607, 612f

trastuzumab (Herceptin), 453b

tree of life, 100, 100f

trehalose, 240f, 241

tretinoin (Retin-A), 357

TRH. See thyrotropin-releasing hormone

triacontanoylpalmitate, 346f

triacylglycerol cycle, 761f, 762, 762f

triacylglycerols, 344, 602

activation of, 603–606, 605f, 606f

in adipose tissue, 851–852, 851f

biosynthesis of, 760–764

digestion of, small intestine absorption, 602–603, 602f

fatty acids in. See fatty acids

germinating seeds and, 735

mobilization of, 603, 604f, 605f

oxidation of. See fatty acid oxidation

as storage lipids

energy storage and insulation provided by, 344–345, 344f

as fatty acid esters of glycerol, 344, 344f

partial hydrogenation of, 345

synthesis of

glyceroneogenesis for, 762–763, 762f, 763f

hormonal regulation of, 760–762, 761f

precursors for, 760, 761f

transport of, 603–606, 605f, 606f

tricarboxylic acid (TCA) cycle, 574. See also citric acid cycle

TriCor. See fenofibrate

trifunctional protein (TFP), 608

genetic defects in, 616–617

triglycerides. See triacylglycerols

trimeric G proteins, 413

trimethoprim, 836f, 838

trimethyllysine, 1038f

triose kinase, 524

triose phosphate isomerase, 185, 517

in glycolytic pathway, 513f, 518f, 524

triose phosphates

in Calvin cycle, 721–724, 725f

$P_{i} -triose$ phosphate antiport system for, 724–725, 725f, 726f

conversion to sucrose and starch, 733f, 734–735, 735f

in glycolytic pathway, 512f, 513f, 514, 516–518, 517f

interconversion of, 513f, 516–518, 518f

movement of, 738–739, 738f

ribulose 1,5-bisphosphate regeneration from, 722, 723f, 728f

trioses, 230, 230f

triplex DNAs, 274, 275f

trisomy, 946b

TrkA. See high-affinity nerve growth factor receptor

tRNA nucleotidyltransferase, 985

tRNAs. See transfer RNAs

tropic hormones (tropins), 847f

tropins. See tropic hormones

tropomyosin, 171, 172f

troponin, 171, 172f, 426

troponin C, 123f

trp operon, 1067–1068, 1067f, 1069f

Trypanosoma brucei gambiense, 201b–202b

trypanosomes, 980

trypsin, 93, 179, 628

zymogens of, 220, 220f

trypsinogen, 220, 220f, 628

tryptophan, 74s, 75, 75b, 75f, 644, 647, 811

biosynthesis of, 811–812, 813f

catabolism of, 640, 640f, 644–647, 644f, 646t, 647f, 648f

E. coli regulation of, 1067–1068, 1067f, 1069f

in membrane proteins, 376f

neurotransmitter synthesis from, 821, 823f

plant substances derived from, 820–821, 822f

properties and conventions associated with, 73t

tryptophan 2,3-dioxygenase, 756b

tryptophan synthase, 812, 813f

Tsien, Roger, 320

Tsix, 907b

t-SNAREs, 383, 384f

TTGACA sequence, 963, 964f

tumor necrosis factor (TNF), in apoptosis, 455, 456f

tumor suppressor genes, 451, 454f, 455

tumor viruses, 990, 990f

tumors

citric acid cycle mutations in, 595, 595f

Complex II mutations in, 667–668

diagnosis of, 528b

gangliosides in, 351

glycolysis in, 526, 527b–528b

loss of cell cycle regulation in

oncogene role in, 451, 452b–453b, 454

tumor suppressor gene role in, 454f, 455

MDR1 role in, 396

p27 protein in, 125

PTEN role in, 437

Ras mutations in, 423

treatment of. See chemotherapeutic drugs

ubiquitination defects in, 1049

tunicamycin, 1042, 1043, 1043f, 1044

turnover, 499

in metabolic regulation, 499f, 499t

turnover number, 193, 193t

Tus-Ter sequence, 927, 927f

26S proteasome, 1048

in protein degradation, 1048–1049, 1049f

two-component system, of bacterial signaling, 447f

two-dimensional electrophoresis, 89, 89f

TX. See thromboxanes

TψC arm, 183f, 1020

type 1 diabetes mellitus, 875

defective glucose transport in, 390b

insulin defects in, 875–877

type 2 diabetes mellitus, 875, 877

insulin defects in, 875–877

insulin resistance in, 877, 878f

management of

biguanides, 879t

diet and exercise, 878–879, 879t

gliflozins, 399

sulfonylurea drugs, 861–862, 879t

surgery, 878–879, 879t

thiazolidinediones, 763–764, 879t

obesity associated with, 877, 878f

SCD role in, 754

type I photosystem, 708

type I topoisomerases, 895, 895f, 896, 896f, 897t

type II photosystem, 707, 708

type II restriction endonucleases, 303, 303t, 304t

type II topoisomerases, 895, 896, 897f, 897t

tyrosine, 74s, 75, 75f, 647, 812

biosynthesis of, 811–812, 814f

catabolism of, 640, 640f, 647–648, 647f, 648f

in general acid-base catalysis, 187f

in membrane proteins, 376f

neurotransmitter synthesis from, 821, 823f

plant substances derived from, 820–821, 822f

properties and conventions associated with, 73t

U

U. See uracil

U1 snRNP, 977, 978f

U2 snRNP, 977, 978f

U4 snRNP, 977, 978f

U5 snRNP, 977, 978f

U6 snRNP, 977, 978f

U11 snRNP, 979

U12 snRNP, 979

UASs. See upstream activator sequences

ubiquinone (Q), 359f, 360, 662

in mitochondrial respiratory chain, 662–663, 663f, 664t

Complex I electron transfer to, 665–667, 665t, 666f

Complex II electron transfer to, 665t, 666f, 667f, 668

electron donation via, 671, 672f

ubiquinone:cytochrome c oxidoreductase, 665t, 666f, 668, 668f, 669, 669f

ubiquitin, 448, 1048

in cyclin degradation, 448, 449f

in protein degradation, 1048–1049, 1048f, 1049t

ubiquitination, 216, 217f

defects in, 1049

ubiquitin-proteasome system, 129f

UCP1. See uncoupling protein 1

UDP. See uridine diphosphate

UDP-glucose, 733, 733f, 733s

in cellulose synthesis, 736–738, 737f

in glycogenesis, 560–563, 563f

in sucrose synthesis, 733–734, 733f

UDP-glucose pyrophosphorylase, 562, 563f

ultraviolet light

amino acid absorption of, 75, 75b, 75f

DNA damage caused by, 281, 282f

nucleotide absorption of, 268, 269f, 279

UMP. See uridylate

UmuC protein, 939f, 940

UmuD protein, 939f, 940

uncompetitive inhibitor, 198, 198f

uncoupling protein 1 (UCP1), 667t, 690, 852

in brown adipose tissue, 690, 690f, 852

leptin stimulation of, 868

in mitochondrial heat production, 690, 690f

underwinding, 891

DNA, 892–893, 893f

linking numbers measuring, 893–895, 894f

topoisomerases changing, 895–898, 895f, 896f, 897f, 897t, 906b

underwound DNA, 891

uniport, 391, 391f

unipotent stem cells, 1091

unity of life, 27

universal electron acceptors, respiratory chain electron funneling to, 661–662, 662t

universe, 20

unsaturated fatty acids

β oxidation of, 611–612, 612f

double bonds in, 342–343

partial hydrogenation of, 345

PUFAs. See polyunsaturated fatty acids

structure and properties of, 342t, 343, 343f

synthesis of, 754, 754f, 755f, 756b–757b

UP. See upstream promoter

UPR. See unfolded protein response

upstream activator sequences (UASs), 1078, 1079f

upstream promoter (UP), 963

uracil (U), 264, 264s, 265t

biosynthesis of, 827, 828f

from cytosine deamination, 280, 281f

degradation of, 834f

in DNA, 833

tautomeric forms of, 268, 268f

uracil DNA glycosylases, 934–935

urate oxidase, 834, 834f

urea, 634

nucleotide catabolism producing, 833–835, 834f, 835f

from pyrimidine degradation, 833–835, 834f, 835f

urea cycle, 633

citric acid cycle links to, 636–637, 636f

defects in, 638–639, 638t, 639f

enzymatic steps of, 633–636, 634f–635f

pathway interconnections reducing energetic cost of, 638

reactions feeding amino groups into, 634f–635f

regulation of, 637–638, 638f

urease, isolation and crystallization of, 179

ureotelic species, 626

uric acid

nucleotide catabolism producing, 833–836, 834f, 835f

from purine degradation, 833–836, 834f, 835f

uricotelic species, 626

uridine, 266s

uridine diphosphate (UDP), 523, 524f

uridine triphosphate (UTP), as chemical energy carrier, 294

uridylate (UMP), 265t, 486

biosynthesis of, 827, 828f, 829f

uridylyltransferase, 803, 804f

urobilinogen, 818, 820f

uronic acid, 237

UTP. See uridine triphosphate

UvrA, 936

UvrB, 936

UvrC, 936

UvrD, 936

V

V segments, 954–955, 954f

$V_{0} .$ See initial rate

vacuoles, 6, 7f

Vagelos, P. Roy, 786b–787b

valdecoxib (Bextra), 758

valine, 74, 74s, 650, 810, 1020s

biosynthesis of, 811f

catabolism of, 640f, 650–651, 652f, 653b, 654f

properties and conventions associated with, 73t

valinomycin, 399, 400f, 667t

van der Waals interactions, 49

homopolysaccharide folding and, 243–244, 244f

protein stability and, 109

in water, 49, 49t, 50t

van der Waals radius, 49, 49t, 50t

vanadate, 392

Varmus, Harold, 990

vascular endothelial growth factor receptor (VEGFR), 438f, 452b

inhibition of, for cancer treatment, 452b–453b

vascular plants

reaction centers of, 708–712, 709f

volatile lipid signals of, 356

vasopressin, water regulation by, 400

vectorial reaction, 666

vectors, cloning. See cloning vectors

VEGFR. See vascular endothelial growth factor receptor

venturicidin, 667t

oxidative phosphorylation inhibition by, 676, 676f

very-long-chain acyl-CoA dehydrogenase (VLCAD), 608

very-low-density lipoproteins (VLDLs), 603, 780

cholesterol transport as, 778f, 778t, 779f, 779t, 780

vesicles, 368f, 368, 370f

composition of, 371f

fusion of, 382–383, 383f, 384f

Viagra. See sildenafil

Vibrio cholerae, 424

Victoria, Queen, 223

video games, 138b–139b

vinblastine, tumor resistance to, 396

Vioxx. See rofecoxib

virtual protein designs, 138b

viruses

cap-snatching by, 974–975

coding information in, 962, 962f

DNA of, 885f, 886–887, 887t, 930

DNA polymerases of, 90

genome of, 301

oncogenes in, 451, 990, 990f

recombinant protein expression using, 311–312, 311f

RNA, 993. See also retroviruses

selectins of, 255, 256f

virusoids, 998

visible light, 703, 703f

vision, GPCR signaling in, 429–431, 429f, 430b, 430f

vitamin A, as hormone precursor, 356–358, 358f

${vitamin A}_{1},$ 357

${vitamin B}_{1}$

deficiency of, 551, 578

thiamine pyrophosphate from, 531f

${vitamin B}_{6}$ , 629

${vitamin B}_{9}$ , 643, 833

${vitamin B}_{12}$ , 613, 614b–615b

deficiency of, 615b, 643

vitamin C, deficiency of, 118b–119b

${vitamin D}_{2},$ 357

${vitamin D}_{3},$ 357

as hormone precursor, 356–358, 357f

vitamin E, 359

as oxidation-reduction cofactor, 359–360, 359f

vitamin K, 359

as oxidation-reduction cofactor, 359–360, 359f

vitamin K antagonists, 222

vitamins, 356

VLCAD. See very-long-chain acyl-CoA dehydrogenase

VLDLs. See very-low-density lipoproteins

$V_{m} .$ See membrane potential

$V_{max} .$ See maximum velocity

voltage-gated ${Ca}^{2 +}$ channels, 443–444, 444f

voltage-gated ion channels, 401, 442

neuronal action potentials produced by, 443–444, 444f

voltage-gated $K^{+} channels,$ 402–403

action potentials produced by, 443–444, 444f

voltage-gated ${Na}^{+}$ channels, 443–444, 444f

v-SNAREs, 383, 384f

V-type ATPases, 394–395, 395f

W

Walker, John E., 678–680

Warburg, Otto, 526

warfarin (Coumadin), 222, 359f, 360

Warshel, Arieh, 138b

waste treatment, anammox bacteria in, 798b–799b

WAT. See white adipose tissue

water

aquaporin transport of, 400–401, 400t

charged solutes in, electrostatic interactions, 46, 46t, 47f, 50t

colligative properties of, 51–53, 51f

crystalline substances in, entropy of dissolving, 47, 47f

defective transport of, 400

as electron donor, 701–702

hydrogen bonding of, 44–45, 44f, 45f, 46f

polar solutes and, 45, 45f, 46f, 50, 50t

ionization of

acid dissociation constants and, 57, 57f

equilibrium constants and, 54–55

pH scale and, 55–56, 55t, 56f

pure water, 54, 54f

titration curves and, 58–59, 58f, 59f

macromolecules in, 49–51, 50f, 50t, 51f

melting point, boiling point, and heat of vaporization of, 44–45

nonpolar compounds in, 47–49, 48f, 49f, 50t

nonpolar gases in, 47, 47t

oxygen-evolving complex and, 714–715, 715f

in photosynthesis, 702–703

as solvent. See aqueous solutions

structure of, 44–45, 44f

van der Waals interactions in, 49, 49t, 50t

water cycle, 461–462, 462f

water elimination, standard free-energy changes of, 469t

water repellents, waxes as, 345–346, 346f

water splitting complex, 714–715, 715f

Watson, James D., 91, 883

DNA structure of, 268–272, 271f, 272f, 915

Waugh, W. A., 119b

waxes, as energy stores and water repellents, 345–346, 346f

weak acids

as buffers, 59–63, 60f, 62f

ionization of

acid dissociation constants and, 57, 57f

equilibrium constants and, 54–55

pH scale and, 55–56, 55t, 56f

pure water, 54, 54f

titration curves and, 58–59, 58f, 59f

$p K_{a},$ 58–59, 58f, 59f

weak bases

as buffers, 59–63, 60f, 62f

ionization of

acid dissociation constants and, 57, 57f

equilibrium constants and, 54–55

pH scale and, 55–56, 55t, 56f

pure water, 54, 54f

titration curves and, 58–59, 58f, 59f

weak interactions

in aqueous solutions, 43–53

charged solutes, 46, 46t, 47f, 50, 50t

colligative properties and, 51–53, 51f

entropy increases, 47, 47f

hydrogen bonding, 44–45, 44f, 45f, 46f

macromolecular structure and function and, 49–51, 50f, 50t, 51f

nonpolar compounds, 47–49, 48f, 49f, 50t

nonpolar gases, 47, 47t

polar solutes, 45, 45f, 46f, 49f, 50, 50t

van der Waals interactions, 49, 49t, 50t

in enzyme-substrate complex

binding energy from, 183

specificity from, 185, 186f

transition state optimization of, 183–186, 183f, 184f, 185f

homopolysaccharide folding and, 243–244, 244f

protein stability and, 107–108

in signal transduction specificity, 409

Weizmann, Chaim, 532

well-fed state

fuel metabolism in, 859–860, 859t, 860f

global carbohydrate metabolism during, 568–570, 569f, 570f

Wernicke-Korsakoff syndrome, 551

Western blot, 167

white adipose tissue (WAT), 851, 851f, 852

white blood cells. See leukocytes

Wieschaus, Eric F., 1087

wild-type cells, 30

Wilkins, Maurice, 270

Winkler, Hans, 301

wobble hypothesis, 1012, 1012f, 1012t

Woese, Carl, 3, 98, 998

Woolley, D. Wayne, 494

work

by electron flow, 488–489

mechanical, muscle production of, 852–855, 854f, 855f, 856b–857b

Wurtz, Charles-Adolphe, 189

Wyman, Jeffries, 158

X

X chromosomes, 907b

X shredder, 325b

XALD. See X-linked adrenoleukodystrophy

xanthine oxidase, 833, 834f, 835–836

inhibition of, 835f, 836

xenobiotics, 691, 850

P-450 enzyme metabolism of, 691, 756b–757b

xeroderma pigmentosum (XP), 454, 932b

Xist (X-inactive specific transcript), 907b

X-linked adrenoleukodystrophy (XALD), 617

XP. See xeroderma pigmentosum

XP genes, 454

x-ray crystallography, 136, 137f

x-ray diffraction, 136–137

of DNA, 270, 271f

protein structure determination using, 136–137, 137f

xylose, 233s

xylulose, 233s

xylulose 5-phosphate

in Calvin cycle, 723f

as key regulator of carbohydrate and fat metabolism, 543–544

in pentose phosphate pathway, 549, 549f, 550f

Y

Y chromosomes, 907b

YACs. See yeast artificial chromosomes

yeast

ethanol fermentation by, 530f, 531–532

PDH complex of, 577f

phospholipid synthesis in, 767–768

recombinant protein expression in, 310–311

regulation of galactose metabolism in, 1081, 1081f, 1082t

replicators of, 928

UASs in, 1078, 1079f

yeast artificial chromosomes (YACs), 307, 891

as cloning vectors, 307–309

yeast two-hybrid analysis, 321–322, 322f

yellow fluorescent protein (YFP), 416b–417b

yogurt, 530

Yonath, Ada E., 1017

Yoshida, Masasuke, 681

Young, William, 514

Z

Z disk, 170–171, 171f

Z scheme, 709, 709f, 710

Zamecnik, Paul, 1005, 1006

zanamivir (Relenza), 255, 256f

zeaxanthin, 360f

Zellweger syndrome, 617

Z-form DNA, 272, 273, 273f

zinc finger, 1061–1062, 1062f

Zocor. See simvastatin

Zuckerkandl, Emile, 98

zwitterions, 77

amino acids as, 77, 78f

zymogens, 220, 220f

in blood coagulation, 220–223, 220f