Title: Jack Sparrow Biochem / Biochemistry / Biochemistry Chapter 9
Tags: #JackSparrow::#B/B::#Biochemistry::#Chapter.9

Q: What are the primary receptors responsible for transport of glucose into and out of cells?
A: Glut 2 and Glut 4

Q: Describe Glut 2
A: Glut 2 is a low affinity glucose transporter found in hepatocytes (liver cells) and pancreatic cells.  The low affinity of this transporter allows it to only shuttle glucose into the liver and pancrease when glucose levels are high (like after a meal).

Q: Describe Glut 4
A: Glut 4 is a glucose transporter found in adipose tissue (fat) and muscle.  The rate of glucose transport for these tissues is increased by insulin.   Insulin stimulates the production of more Glut4 receptors to line the membrane

Q: In muscles, excess glucose is converted into [glycogen or DHAP?]
A: glycogen

Q: In adipocytes, excess glucose is converted into [glycogen or DHAP?]
A: DHAP
Extra: DHAP is converted into Glyercol Phosphate to store incoming fatty acids at triacylglycerols.

Q: What is glycolysis?
A: Glycolysis is a cytoplasmic pathway that converts glucose into two pyruvate molecules, releasing a modest amount of energy.

Q: What is the first step of Glycolysis?
A: An ATP molecule is used by Hexokinase to phosphorlyate Glucose to Glucose-6-P.

Q: What is the second step of Glycolysis?
A: Isomerase isomerizes Glucose-6-P to Fructose-6-P.

Q: What is the third step of Glycolysis?
A: Phosphofructokinase-1 spends 1 ATP to phosphorlyate Fructose 6-p to Fructose 1,6-bis P

Q: What is the 4th step of Glycolysis?
A: Aldolase cleaves Fructose 1,6-bis P into Glyceraldehyde-3-P and Dihydroxyacetone P (DHAP)

Q: What is the 5th step of Glycolysis?
A: Glyceraldehyde 3-P is the only molecule that can continue down the glycolytic pathway, and so the DHAP molecule from the cleavage of Fructose 1,6 -bis P is converted into Glyceraldehyde 3-P by an Isomerase for a total of two Glyceraldehyde 3-P's

Q: What is the 6th step of Glycolysis?
A: Glyceraldehyde 3-P Dehydrogenase uses 2 Phosphates and 2 NAD+'s to oxidize 2 molecules of Glyceraldehyde 3-P to 1,3-Bisphosphoglycerate, producing 2 NADH's.

Q: What is the 7th step of Glycolysis?
A: Phosphoglycerate Kinase spends 2 ADPs to convert 2 1,3-Bisphoglycerates into 2 3-Phosphoglycerates and generate 2 ATP's.

Q: What is the 8th step of Glycolysis?
A: Mutase converts 2 3-Phosphoglycerates into 2 2-Phosphoglycerates.

Q: What is the 9th step of Glycloylsis?
A: Enolase converts 2 2-Phosphoglycerates into 2 Phosphoenolpyruvates (PEP)

Q: What is the 10th step of Glycolysis?
A: Pyruvate Kinase uses 2 ADPs to convert 2 PEPs into 2 Pyruvates and 2 ATPs

Q: What is the overall metabolic reaction of Glycolysis?
A: 2ADP + 2 ATP + 2 NAD^+ + Glucose -> 4 ATP + 2 NADH + 2 Pyruvates
There are also some hydrogen ions and water molecules but they aren't as important.

Q: What is the investment phase of glycolysis?
A: The investment phase refers to the consumption of ATP in steps 1 and 3 of Glycoylsis.  At this point, the cell has actually made an energy investment to metabolize glucose.  This investment pays off later when ATP is released by substrate level phosphorylation.

Q: What is AMP and what is its general signalling function?
A: AMP is like ATP, but instead of three phosphates there is only one.  AMP basically acts as a "low energy" signal and will affect enzymes in the glycolytic pathway accordingly.  For this reason, expect AMP to activate things that produce energy and inactivate things that consume it.

Q: What is the difference between Hexokinase and Glucokinase?
A: Hexokinase is present in most tissues and phosphorylates 6 carbon sugars.  It is a high affinity enzyme (low km).
Glucokinase is present only in hepatocytes and pancreatic cells and only phosphorylates glucose.  It is a low affinity enzyme (high km).

Q: What is a rate limiting enzyme?
A: In a series of reactions, one of them will be slower than the rest and therefore act as a bottleneck.  The rate limiting enzyme is the enzyme associated with the rate limiting step.

Q: What is the rate limiting step of Glycolysis?
A: Step 3, the conversion of Fructose 6-P into Fructose 1,6-bis P by Phosphofructokinase-1

Q: Describe the regulation of Phosphofructose kinase 1 (PFK-1)
A: PFK-1 is subject to negative feedback in the form of inhibition by ATP and Citrate.  This makes sense, because if you have a lot of energy and metabolic products (citrate), you can turn glycolysis off.
PFK-1 is also subject to activation by AMP.  This makes sense because if you have low energy (high AMP), you can turn glycolysis on.

Q: How do Insulin and Glucagon interact with Glycolysis in the liver?
A: Insulin and Glucagon act on an enzyme called Phosphofructose Kinase 2 (PFK2) which converts Fructose 6-P into Fructose 2,6-bis P.  Fructose 2,6-bis P activates PFK 1.
Insulin increases the activity of PFK 2, which increases Fructose 2,6-bis P, which leads to an increase in PFK1 activity.
Glucagon has the exact opposite effect on PFK 2.

Q: Glycolysis is [anaerobic or aerobic]
A: anaerobic

Q: In the presence of oxygen, pyruvate will [ferment or proceed to citric acid cycle?]
A: ferment

Q: What is substrate-level phosphorylation?
A: Substrate level phosphorylation refers to the anaerobic production of ATP in steps 7 and 10 of glycolysis.  This is different from oxidative phosphorylation which is the generation of ATP from the proton gradient in the mitochondria.

Q: Describe the regulation of Pyruvate Kinase
A: Pyruvate Kinase is subject to feed-forward activation by Fructose 1,6-bisphosphate from step 3 of Glycolysis.  It makes sense because if you're running glycolysis hard (lots of Fructose 1,6-bisphosphate) you want the enzymes associated with glycolysis activated.

Q: What is fermentation?
A: Fermentation is what happens to pyruvate in the absence of oxygen.  In order to regenerate the two NAD^+s generated earlier in glycolysis, Lactate Dehydrogenase uses 2 NADHs and 2 Pyruvates to produce 2 NAD^+s and 2 Lactates.
Some organisms use alcohol dehydrogenase instead to convert pyruvate into ethanol molecules.  The end result is the same, the regeneration of two NAD^+s .

Q: Describe the metabolic crossroad of Dihydroxyacetone Phosphate (DHAP)
A: DHAP is usually just converted right into G3P, but in hepatic and adipose tissue DHAP can be converted into Glycerol-3-P which can be converted to Glycerol, the backbone of triacylglycerols.

Q: What is an irreversible enzyme?
A: An irreversible enzyme is an enzyme that pushes a reaction forward so hard that it is essentially unreversable.  These steps are important to note because, unlike the other steps of metabolism, they aren't in much of an equilibrium.  At these steps, the reaction goes almost exclusively forward.

Q: What are the irreversible enzymes of Glycolysis?
A: 1.  Hexokinase or Glucokinase
2.  PFK-1
3.  Pyruvate Kinase
MNEMONIC: How Glucose Pushes Forward the Process: Kinases

Q: What is a unique modification made to 1,3-BPG in eryhtrocytes?
A: In erythrocytes, there is an enzyme called Bisphosphoglycerate mutase which produces 2-3, Bisphosphoglycerate (2,3-BPG) from 1,3-BPG.
2,3-BPG binds to hemoglobin, reducing its affinity for oxygen and shifting the curve right.

Q: Describe the Regulation of Hexokinase?
A: Hexokinase is subject to negative feedback in the form of inhibition by Glucose-6-Phosphate

Q: What are the main metabolic pathways for non-glucose monosaccharides?
A: 1.  Galactose metabolism
2.  Fructose metabolism

Q: Describe the Galatactose Metabolic Pathway
A: Galactokinase uses ATP to convert Galactose to Galactose 1-P.
Uridyltransferase and an Epimerase convert Galactose 1-P to Glucose 1-P
At this point, Glucose 1-P will interact with all the normal metabolic pathways.

Q: Describe the Fructose Metabolic pathway.
A: Fructokinase converts Fructose into Fructose-1P.
Aldolase converts Fructose-1P into DHAP, which can enter the glycolytic pathway and Glyceraldehyde.
Glyceraldehyde can be converted into Glyceraldehyde 3-P, which can also enter the glycolytic pathway.

Q: What happens to Pyruvate in the presence of oxygen?
A: In the presence of oxygen, Pyruvate Dehydrogenase uses CoA and NAD^+ to produce Acetyl-CoA, an NADH, and CO_2.
Acetyl-CoA can then enter the citric acid cycle or be used for fatty acid synthesis.
Acetyl-CoA negatively inhibits Pyruvate Dehydrogenase.

Q: What are the three possible fates for Pyruvate?
A: 1.  Conversion into acetyl-coa by Pyruvate Dehydrogenase (PDH)
2.  Conversion into lactate by lactate dehydrogenase
3.  Conversion to oxaloacetate by pyruvate carboxylase.

Q: What is Glycolysis?
A: Glycolysis is the breakdown of glucose for energy.

Q: What is glycogenesis?
A: Glycogensis is the synthesis of glycogen

Q: What is glycogenolysis?
A: Glycogenolysis is the breakdown of glycogen for energy.

Q: What is gluconeogenesis?
A: Gluconeogenesis is the synthesis of glucose.

Q: Describe Glycogenesis
A: Glucose-6-Phopshate from Glycolysis is converted into Glucose 1-Phosphate.
Glucose 1-Phosphate is activated with a UTP to make UDP-Glucose
UDP-Glucose is added to the growing alpha 1-4 Glycogen chain by Glyocgen Synthase, the rate limiting step of Glycogenesis.

Q: Describe the regulation of Glycogen Synthase
A: Glycogen synthase is activated in times of high sugar.  Therefore, it is stimulated by the presence of Glucose-6 Phosphate and Insulin.
It is deactivated in times of sugar need.  Therefore it is inibited by the presence of Glucagon(liver), Epinephrine(liver and muscle), and AMP(muscle).

Q: Describe the regulation of Glycogen phosphorylase
A: Glycogen phosphorylase is activated in times of sugar need.  Therefore, it is stimulated by the presence of glucagon, epinephrine, and AMP.
It is deactivated in times of sugar storage.  Therefore it is inibited by the presence Insulin and ATP.

Q: What is the role of branching enzyme?
A: While Glyocgen Synthase introduces a-1,4 bonds to the glycogen chain, branching enzyme hydrolyzes a-1,4 bonds and moves them to a 6-position in order to make a branch.

Q: What is glycogenin?
A: Glycogenin is a core protein that glycogen uses as its core and starting synthesis point.

Q: Describe Glycogenolysis
A: Glycogen Phosphorylase, the rate limiting enzyme of Glycogenolysis, cleaves a Glucose-1 Phosphate from the glycogen chain.  The G1P can be converted to G6P and enter relevant metabolic pathways.

Q: What are the two debranching enzymes?
A: 1.  a-1,4:a-1,4 transferase
2.  a-1,6 Glucosidase

Q: How does debranching of glycogen occur?
A: 1.  The closest a-1,4 bond is cleaved and transfered to a different chain by a-1,4 transferase.
2.  The single a-1,6 bond is cleaved by a-1,6 glucosidase.  This step is interesting because the glucose liberated is an actual glucose, not a phosphorylated glucose.

Q: What is an isoform?
A: An isoform is a slightly different version of the same protein.

Q: What are the important metabolic intermediates that can be used to make glucose through gluconeogenesis?
A: 1.  Glycerol 3-Phosphate (From stored fats or triacylglycerols)
2.  Lactate (from anaerobic glycolysis)
3.  Glucogenic amino acid (from muscle breakdown)

Q: What are the two type of amino acids in regards to metabolism?
A: 1.  Glucogenic
2.  Ketogenic

Q: What are glucogenic amino acids?
A: Glucogenic amino acids (every single one except leucine and lysine) are amino acids that can be converted into intermediates that feed into gluconeogenesis.

Q: What are ketogenic amino acids?
A: Ketogenic amino acids are amino acids that can be converted into ketone bodies. Ketogenic amino acids include leucine and lysine (both are exclusively ketogenic), as well as phenylalanine, isoleucine, threonine, tryptophan, and tyrosine (these 5 are both ketogenic and glucogenic)

Q: Describe Gluconeogenesis
A: Gluconeogenesis is mostly just the reverse of glycolysis.  The only difference is that the three irreversible steps of glycolysis must be bypassed by gluconeogenesis specific enzymes.  These enzymes are Pyruvate Carboxylase + Phosphoenolpyruvate Carboxykinase (PEPCK), Fructose-1,6-bisphosphatase, and Glucose-6-phosphatase.

Q: Describe pyruvate carboxlyase
A: Pyruvate carboxylase is a mitochondrial enzyme that is activated by acetyl-coa.  It converts Pyruvate into Oxaloacetate during times of high energy when glucose consumption is not required.

Q: Describe PEPCK
A: PEP CK is an enzyme in the cytoplasm that is activated by glucagon and cortisol.  It uses 1 GTP to convert Oxaloacetate to PEP in the service of gluconeogenesis.

Q: Describe Fructose-1,6-bisphosphatase
A: Fructose-1,6-bisphosphotase is the rate limiting step of Gluconeogenesis.  It converts Fructose-1,6, Bisphosphate into Fructose - 6 Phosphate
Fructose-1,6 bisphosphotase is activated by ATP and inhibited by AMP and Fructose 2,6-bisphosphate.

Q: Where do the acetyl-coas used in Gluconeogenesis come from?
A: Beta oxidation, which means they come from fatty acids.  This is an important distinction, because if you just used the acetyl-coa's that glycolysis makes, you'd just be going around in a circle.  Because the fatty acids are what supply the acetyl-coa, the system is a lot more efficient and flexible.  (storage form of energy, fat, can be converted into the actual usable form of energy, glucose.)

Q: Describe Glucose-6-Phosphotase
A: Glucose-6-Phosphotase converts Glucose-6 Phosphate back into Glucose, thus completing gluconeogenesis.

Q: What is the Pentose Phosphate Pathway?
A: The Pentose Phosphate Pathway is a metabolic pathway for producing NADPH and Ribose-5-Phosphate for nucleotide synthesis.
The Pentose Phosphate Pathway occurs in the cytoplasm.

Q: What is the difference between NADPH and NADH?
A: NADH is an energy carrier used to generate ATP.
NADPH is used in biosynthesis of large molecules, the immune system, and to protect against oxidative damage.

Q: What is the rate limiting step of the pentose phosphate pathway?
A: The rate limiting step of the PPP is the conversion of Glucose-6 P and NADP+ to 6-Phosphogluconate and NADPH by Glucose-6P Dehydrogenase.  This enzyme is activated by insulin because the abundance of sugar entering the cell means there is enough glucose to run the PPP for NADPH's.

Q: NADPH is an [oxidizing or reducing agent?]
A: reducing agent

Q: NADH is an [oxidizing or reducing agent?]
A: reducing agent
Extra: and thus oxidizes itself in the process