13.2 Chemical Logic and Common Biochemical Reactions in Chapter 13 Introduction to Metabolism

13.2 Chemical Logic and Common Biochemical Reactions

The biological energy transductions we are concerned with in this book are chemical reactions. Cellular chemistry does not encompass every kind of reaction learned in a typical organic chemistry course. Which reactions take place in biological systems and which do not is determined by (1) their relevance to that particular metabolic system and (2) their rates. Both considerations play major roles in shaping the metabolic pathways we consider throughout the rest of the book. A relevant reaction is one that makes use of an available substrate and converts it to a useful product. However, even a potentially relevant reaction may not occur. Some chemical transformations are too slow (have activation energies that are too high) to contribute to living systems, even with the aid of powerful enzyme catalysts. The reactions that do occur in cells represent a toolbox that evolution has used to construct metabolic pathways that circumvent the “impossible” reactions. Learning to recognize the plausible reactions can be a great aid in developing a command of biochemistry.

Even so, the number of metabolic transformations taking place in a typical cell can seem overwhelming. Most cells have the capacity to carry out thousands of specific, enzyme-catalyzed reactions: for example, transformation of a simple nutrient such as glucose into amino acids, nucleotides, or lipids; extraction of energy from fuels by oxidation; and polymerization of monomeric subunits into macromolecules.

Biochemical Reactions Occur in Repeating Patterns

To study these reactions, some organization is essential. There are patterns within the chemistry of life; you do not need to learn every individual reaction to comprehend the molecular logic of biochemistry. Most of the reactions in living cells fall into one of five general categories: (1) reactions that make or break carbon–carbon bonds; (2) internal rearrangements, isomerizations, and eliminations; (3) free-radical reactions; (4) group transfers; and (5) oxidation-reductions. We discuss each of these in more detail below and refer to some examples of each type in later chapters. Note that the five reaction types are not mutually exclusive; for example, an isomerization reaction may involve a free-radical intermediate.

Before proceeding, however, we should review two basic chemical principles. First, a covalent bond consists of a shared pair of electrons, and the bond can be broken in two general ways (Fig. 13-1). In homolytic cleavage, each atom leaves the bond as a radical, carrying one unpaired electron. In heterolytic cleavage, which is more common, one atom retains both bonding electrons. The species most often generated when $C — C$ $upper C em-dash upper C$ and $C — H$ $upper C em-dash upper H$ bonds are cleaved are illustrated in Figure 13-1. Carbanions, carbocations, and hydride ions are highly unstable; this instability shapes the chemistry of these ions, as we shall see.

A figure shows an example of homolytic cleavage of a C to H bond, an example of homolytic cleavage of a C to C bond, two examples of heterolytic cleavage of a C to H bond, and one example of heterolytic cleavage of a C to C bond. — FIGURE 13-1 Two mechanisms for cleavage of a $C — C$ $upper C em-dash upper C$ or $C — H$ $upper C em-dash upper H$ bond. In a homolytic cleavage, each atom keeps one of the bonding electrons, resulting in the formation of carbon radicals (carbons having unpaired electrons) or uncharged hydrogen atoms. In a heterolytic cleavage, one of the atoms retains both bonding electrons. This can result in the formation of carbanions, carbocations, protons, or hydride ions.

FIGURE 13-1 Two mechanisms for cleavage of a $C — C$ $upper C em-dash upper C$ or $C — H$ $upper C em-dash upper H$ bond. In a homolytic cleavage, each atom keeps one of the bonding electrons, resulting in the formation of carbon radicals (carbons having unpaired electrons) or uncharged hydrogen atoms. In a heterolytic cleavage, one of the atoms retains both bonding electrons. This can result in the formation of carbanions, carbocations, protons, or hydride ions.

The first two reactions show homolytic cleavage. First reaction: C has four bonds with the right-hand extending to H. Left- and right-pointing arrows show that this undergoes a reversible reaction to produce C with three bonds and a single red dot to its right, labeled carbon radical, plus H with a single red dot to its left, labeled H atom. Second reaction: C has four bonds with the right-hand bond extending to C on its right that also has four bonds in total. Left- and right-pointing arrows show that this undergoes a reversible reaction to produce C with three bonds and a single red dot to its right and C with three bonds and a single red dot to its left in place of the fourth bond. These products are labeled carbon radicals. The next three reactions show heterolytic cleavage. First reaction: C has four bonds with the right-hand extending to H. Left- and right-pointing arrows show that this undergoes a reversible reaction to produce C with three bonds and a pair of red dots and a red negative charge to its right, labeled carbanion, plus H with a red plus sign to its right, labeled proton. Second reaction: C has four bonds with the right-hand extending to H. Left- and right-pointing arrows show that this undergoes a reversible reaction to produce C with three bonds and a red positive charge to its right, labeled carbocation, plus H with a red pair of electrons and a red negative charge to its right, labeled hydride. Third reaction: C has four bonds with the right-hand bond extending to C on its right that also has four bonds in total. Left- and right-pointing arrows show that this undergoes a reversible reaction to produce C with three bonds and a pair of red dots and a negative charge to its right, labeled carbanion, plus C with three bonds and a red positive charge to its left in place of a fourth bond, labeled carbocation.

The second basic principle is that many biochemical reactions involve interactions between nucleophiles (functional groups rich in and capable of donating electrons) and electrophiles (electron-deficient functional groups that seek electrons). Nucleophiles combine with and give up electrons to electrophiles. Common biological nucleophiles and electrophiles are shown in Figure 13-2. Note that a carbon atom can act as either a nucleophile or an electrophile, depending on which bonds and functional groups surround it.

A figure shows six examples of common nucleophiles and four examples of common electrophiles with arrows showing the movement of electron pairs. — FIGURE 13-2 Common nucleophiles and electrophiles in biochemical reactions. Chemical reaction mechanisms, which trace the formation and breakage of covalent bonds, are communicated with dots and curved arrows, a convention known informally as “electron pushing.” A covalent bond consists of a shared pair of electrons. Nonbonded electrons important to the reaction mechanism are designated by dots (:). Curved arrows () represent the movement of electron pairs. For movement of a single electron (as in a free-radical reaction), a single-headed (fishhook-type) arrow is used (). Most reaction steps involve an unshared electron pair.

FIGURE 13-2 Common nucleophiles and electrophiles in biochemical reactions. Chemical reaction mechanisms, which trace the formation and breakage of covalent bonds, are communicated with dots and curved arrows, a convention known informally as “electron pushing.” A covalent bond consists of a shared pair of electrons. Nonbonded electrons important to the reaction mechanism are designated by dots (:). Curved arrows () represent the movement of electron pairs. For movement of a single electron (as in a free-radical reaction), a single-headed (fishhook-type) arrow is used (). Most reaction steps involve an unshared electron pair.

There are six examples of common nucleophiles as follows. Negatively charged oxygen (as in an unprotonated hydroxyl group or an ionized carboxylic acid): O with a bond to the left and a red pair of electrons on its right beneath a minus symbol has a red curved arrow from the minus symbol and pair of electrons to the right. Negatively charged sulfhydryl: S with a bond to the left and a red pair of electrons on its right beneath a minus symbol has a red curved arrow from the minus symbol and pair of electrons to the right. Carbanion: C with bonds above, to the left, and below and a red pair of electrons on its right beneath a minus symbol has a red curved arrow from the minus symbol and pair of electrons to the right. Uncharged amine group: N with bonds to the right, below, and to the left and a red pair of electrons above has a red curved arrow from the pair of electrons symbol to the right. Imidazole: A five-membered ring with a bond attached to its upper left vertex, N substituted for C at its lower left vertex and bonded to H, double bonds at its upper left and lower right vertices, and N substituted for C at its upper right vertex with red pair of electrons on its right has a red curved arrow from the pair of electrons to the right. Hydroxide ion: H is bonded to O with a red pair of electrons and a minus symbol to its right has a red curved arrow from the minus symbol and pair of electrons to the right. There are four examples of common electrophiles as follows. Carbon atom of a carbonyl group (the more electronegative atom of the carbonyl group pulls electrons away from the carbon): C with bonds to the left and right and a double bond to O below is shown beneath R with a red pair of electrons to its left. Red curved arrows point from the electrons on R to C and from the double bond to O. Protonated imine group (activated for nucleophilic attack at the carbon by protonation of the imine: C with bonds to its upper and lower left is double bonded to N plus to its right with a bonds to its right and to H below. R above has a red pair of electrons. Red curved arrows point from the electrons on R to C and from the double bond to N. Phosphorus of a phosphate group: P with single bonds to three O minus and a double bond to O is shown with R with a red pair of electrons to its upper right. Red curved arrows point from the electrons on R to P and from the double bond between P and O to the O at the right end of the double bond. Proton: H plus is shown with R with a red pair of electrons above. Red curved arrows point from the electrons on R to H.

Reactions That Make or Break Carbon–Carbon Bonds

Heterolytic cleavage of a $C — C$ $upper C em-dash upper C$ bond yields a carbanion and a carbocation (Fig. 13-1). Conversely, the formation of a $C — C$ $upper C em-dash upper C$ bond involves the combination of a nucleophilic carbanion and an electrophilic carbocation. Carbanions and carbocations are generally so unstable that their formation as reaction intermediates can be energetically unfeasible, even with enzyme catalysts. For the purpose of cellular biochemistry, they are impossible reactions — unless chemical assistance is provided in the form of functional groups containing electronegative atoms (O and N) that can alter the electronic structure of adjacent carbon atoms so as to stabilize and facilitate the formation of carbanion and carbocation intermediates.

Carbonyl groups are particularly important in the chemical transformations of metabolic pathways. The carbon of a carbonyl group has a partial positive charge due to the electron-withdrawing property of the carbonyl oxygen, and so is an electrophilic carbon (Fig. 13-3a). A carbonyl group can thus facilitate the formation of a carbanion on an adjoining carbon by delocalizing the carbanion’s negative charge (Fig. 13-3b). An imine group (see Fig. 1-14) can serve a similar function (Fig. 13-3c). The capacity of carbonyl and imine groups to delocalize electrons can be further enhanced by a general acid catalyst or by a metal ion $({Me}^{2 +})$ $left-parenthesis Me Superscript 2 plus Baseline right-parenthesis$ such as ${Mg}^{2 +}$ $Mg Superscript 2 plus$ (Fig. 13-3d).

A four-part figure shows chemical properties of carbonyl groups, including the distribution of partial positive charge, delocalization of electrons in part b, interaction with imines in part c, and the effects of interactions with M e 2 plus or a general acid in part d. — FIGURE 13-3 Chemical properties of carbonyl groups. (a) The carbon atom of a carbonyl group is an electrophile by virtue of the electron-withdrawing capacity of the electronegative oxygen atom, which results in a structure in which the carbon has a partial positive charge. (b) Within a molecule, delocalization of electrons into a carbonyl group stabilizes a carbanion on an adjacent carbon, facilitating its formation. (c) Imines function much like carbonyl groups in facilitating electron withdrawal. (d) Carbonyl groups do not always function alone; their capacity as electron sinks often is augmented by interaction with either a metal ion ( ${Me}^{2 +}$ $Me Superscript 2 plus$ , such as ${Mg}^{2 +}$ $Mg Superscript 2 plus$ ) or a general acid (HA).

FIGURE 13-3 Chemical properties of carbonyl groups. (a) The carbon atom of a carbonyl group is an electrophile by virtue of the electron-withdrawing capacity of the electronegative oxygen atom, which results in a structure in which the carbon has a partial positive charge. (b) Within a molecule, delocalization of electrons into a carbonyl group stabilizes a carbanion on an adjacent carbon, facilitating its formation. (c) Imines function much like carbonyl groups in facilitating electron withdrawal. (d) Carbonyl groups do not always function alone; their capacity as electron sinks often is augmented by interaction with either a metal ion ( ${Me}^{2 +}$ $Me Superscript 2 plus$ , such as ${Mg}^{2 +}$ $Mg Superscript 2 plus$ ) or a general acid (HA).

Part a shows C bonded to the left and right and double bonded to O above. O is labeled Greek letter delta minus and C is labeled Greek letter delta plus. Part b shows C bonded to the left, double bonded to O above, and bonded to C on the right that has bonds to its right and below, a red pair of electrons, and a red minus sign. Curved arrows point from the double bond between C and O to the double-bonded O and from the pair of electrons to the bond between the carbons. A double headed arrow points to C on the right that is bonded to the left, bonded to O minus above, and double bonded to C on the right that is further bonded to the right and below. Part c shows a left-hand C that is further bonded above, to the left, and below and to a central C on the right that is double bonded to N H 2 above with a positive charge on N and to a right-hand C that is bonded to its right and below and that has a red pair of electrons above and a red minus sign. Curved arrows point from the double bond between the central C and N to the N and from the pair of electrons to the bond between the central and right-hand carbons. A double-headed arrow points to C on the right at the left side of a similar chain of three C. This molecule has a left-hand C further bonded above, to the left, and below and bonded to a central C bonded to N H 2 above and double bonded to C on the right that is further bonded to the right and below. Part d shows C further bonded to the left and right and double bonded to O above. There is a dashed line between O and M e 2 plus to the upper right. To its right, there is a similar C double bonded to O with a dashed line to H A to its upper right.

The importance of a carbonyl group is evident in three major classes of reactions in which $C — C$ $upper C em-dash upper C$ bonds are formed or broken (Fig. 13-4): aldol condensations, Claisen ester condensations, and decarboxylations. In each type of reaction, a carbanion intermediate is stabilized by a carbonyl group, and in many cases another carbonyl provides the electrophile with which the nucleophilic carbanion reacts.

A figure shows three common reactions that break and form C to C bonds in biological systems: aldol condensation, Claisen ester condensation, and decarboxylation of a Greek letter beta-keto acid. — FIGURE 13-4 Some common reactions that form and break $C — C$ $upper C em-dash upper C$ bonds in biological systems. For both the aldol condensation and the Claisen condensation, a carbanion serves as nucleophile and the carbon of a carbonyl group serves as electrophile. The carbanion is stabilized in each case by another carbonyl at the adjoining carbon. In the decarboxylation reaction, a carbanion is formed on the carbon shaded blue as the ${CO}_{2}$ $CO Subscript 2$ leaves. The reaction would not occur at an appreciable rate without the stabilizing effect of the carbonyl adjacent to the carbanion carbon. Wherever a carbanion is shown, a stabilizing resonance with the adjacent carbonyl, as shown in Figure 13-3b, is assumed. An imine (Fig. 13-3c) or other electron-withdrawing group (including certain enzymatic cofactors such as pyridoxal) can replace the carbonyl group in the stabilization of carbanions.

Aldol condensation: R superscript 1 is bonded to C double bonded to O above and bonded to C on the right that has a red pair of electrons and a minus symbol and is bonded to R superscript 2 above and bonded to H below. A red molecule has C bonded to R superscript 3 above, double bonded to O on the right, and bonded to R superscript 4 below. Red arrows point from the pair of electrons on C on the left-hand molecule to the red C of the right-hand molecule and from the double bond between C and O in the red right-hand molecule. A right-pointing arrow with the addition of H plus show that this yields R superscript 1 bonded to C double bonded to O above and bonded to C on the right bonded to R superscript 2 above, bonded to H below, and connected by a red bond on the right to C of a red part of the molecule. This red C is bonded to R superscript 3 above, O H to the right, and R superscript 4 below. Claisen ester condensation: C o A bonded to S is bonded to C double bonded to O above and bonded to C on the right bonded that has a red pair of electrons and a minus symbol and is bonded to H above and below. A red molecule has C bonded to R superscript 1 above, bonded to S below that is further bonded to R superscript 2, and double bonded to O on the right. Curved arrows point from the pair of electrons on C to C of the red molecule and from the bond between this red C and the red S to the red S. An arrow pointing right is joined by a curved arrow showing the addition of H plus and the loss of a molecule with H bonded to red highlighted S connected by a red bond to red highlighted R superscript 2. This yields C o A bonded to S bonded to C double bonded to O above and bonded to C to the right that is bonded to H above and below and connected by a red bond to red C bonded to red superscript 1 above and connected by a red double bond to O to the right. Decarboxylation of a Greek letter beta-keto acid. R is bonded to C double bonded to O above and bonded to a C in a blue square to the right that is bonded to H above and below and to a red highlighted C to the right connected by a red double bond to red O to its upper right and connected by a red bond to O minus to its lower right. Curved arrows point from the nonhighlighted double bond between C and O to blue highlighted H plus above, from the bond to the right of the C in the blue box to the bond to the left of the C in the blue box, and from the red highlighted O minus to the bond connecting that O minus to the red highlighted C. A right-pointing arrow is joined by a curved arrow showing the addition of blue highlighted H plus and loss of red highlighted C O 2. This yields R bonded to C bonded to O above that is further bonded to blue highlighted H and double bonded to C bonded to H above and below. Red curved arrows point from the bond between blue highlighted H and O to the bond between the same O and C and from the double bond to red highlighted H plus. A right-pointing arrow is joined by a curved arrow showing the addition of red highlighted H plus and the loss of blue highlighted H plus. This produces R bonded to C double bonded to O above and bonded to C on the right bonded to H above and below and bonded to red highlighted H to the right.

An aldol condensation is a common route to the formation of a $C — C$ $upper C em-dash upper C$ bond; the aldolase reaction, which converts a six-carbon compound to two three-carbon compounds in glycolysis, is an aldol condensation in reverse (see Fig. 14-5). In a Claisen condensation, the carbanion is stabilized by the carbonyl of an adjacent thioester; an example is the synthesis of citrate in the citric acid cycle (see Fig. 16-9). Decarboxylation also commonly involves the formation of a carbanion stabilized by a carbonyl group; the acetoacetate decarboxylase reaction that occurs in the formation of ketone bodies during fatty acid catabolism provides an example (see Fig. 17-16). Entire metabolic pathways are organized around the introduction of a carbonyl group in a particular location so that a nearby carbon–carbon bond can be formed or cleaved. In some reactions, an imine or a specialized cofactor such as pyridoxal phosphate plays the electron-withdrawing role, instead of a carbonyl group.

The carbocation intermediate occurring in some reactions that form or cleave $C — C$ $upper C em-dash upper C$ bonds is generated by the elimination of an excellent leaving group, such as pyrophosphate (see “Group Transfer Reactions” below). An example is the prenyltransferase reaction (Fig. 13-5), an early step in the pathway of cholesterol biosynthesis.

A figure shows the role of carbocations in carbon-carbon bond formation using the sequence of reactions that converts dimethylallyl pyrophosphate to geranyl pyrophosphate. — FIGURE 13-5 Carbocations in carbon–carbon bond formation. In one of the early steps in cholesterol biosynthesis, the enzyme prenyltransferase catalyzes condensation of isopentenyl pyrophosphate and dimethylallyl pyrophosphate to form geranyl pyrophosphate (see Fig. 21-36). The reaction is initiated by elimination of pyrophosphate from the dimethylallyl pyrophosphate to generate a carbocation, stabilized by resonance with the adjacent $C ═ C$ $upper C box drawings double horizontal upper C$ bond.

FIGURE 13-5 Carbocations in carbon–carbon bond formation. In one of the early steps in cholesterol biosynthesis, the enzyme prenyltransferase catalyzes condensation of isopentenyl pyrophosphate and dimethylallyl pyrophosphate to form geranyl pyrophosphate (see Fig. 21-36). The reaction is initiated by elimination of pyrophosphate from the dimethylallyl pyrophosphate to generate a carbocation, stabilized by resonance with the adjacent $C ═ C$ $upper C box drawings double horizontal upper C$ bond.

Dimethylallyl pyrophosphate has a four-carbon chain with C 1 bonded to 2 H and to O further bonded to P double bonded to O above, bonded to O minus below, and bonded to O to the left bonded to P double bonded to O above and bonded to O minus to the left and below; C 2 bonded to H and double bonded to C 3; and C 3 bonded to 2 C H 3. An arrow pointing down is accompanied by arrows showing the loss of P P subscript i and the addition of isopentenyl pyrophosphate. This yields isopentenyl pyrophosphate and a dimethylallylic carbocation. Isopentenyl pyrophosphate has a similar structure to dimethylallyl pyrophosphate except that C 2 is bonded to 2 H, there is a single bond between C 2 and C 3, C 3 is bonded to C H 3 and has a double bond to C 4, and C 4 is bonded to 2 H. The dimethyllalylic carbocation has C plus bonded to 2 H and bonded to C H double bonded to C bonded to C H 3 above and below. Red curved arrows point from the bond between C 2 and H to the bond between C 2 and C 3 in isopentenyl pyrophosphate and from the double bond in isopentenyl pyrophosphate to the C plus in the dimethylallylic carbocation. An arrow pointing down has a branched arrow to show the loss of H plus. Geranyl pyrophosphate has two phosphate groups joined to an eight-carbon chain. C 1 is bonded to 2 H and to O further bonded to P double bonded to O above, bonded to O minus below, and bonded to O to the left bonded to P double bonded to O above and bonded to O minus to the left and below; C 2 is bonded to H and double bonded to C 3; C 3 is bonded to C H 3; C 4 is bonded to 2 H; C 5is bonded to 2 H; C 6 is double bonded to C 7; C 7 is bonded to C H 3; and C 8 is bonded to 3 H.

Internal Rearrangements, Isomerizations, and Eliminations

Another common type of cellular reaction is an intramolecular rearrangement in which redistribution of electrons results in alterations of many different types without a change in the overall oxidation state of the molecule. For example, different groups in a molecule may undergo oxidation-reduction, with no net change in oxidation state of the molecule; groups at a double bond may undergo a cis-trans rearrangement; or the positions of double bonds may be transposed. An example of an isomerization entailing internal oxidation-reduction is the formation of fructose 6-phosphate from glucose 6-phosphate in glycolysis (Fig. 13-6; this reaction is discussed in detail in Chapter 14): C-1 is reduced (aldehyde to alcohol) and C-2 is oxidized (alcohol to ketone). Figure 13-6b shows the details of the electron movements in this type of isomerization. A cis-trans rearrangement is illustrated by the prolyl cis-trans isomerase reaction in the folding of certain proteins (see p. 133). A simple transposition of a $C ═ C$ $upper C box drawings double horizontal upper C$ bond occurs during metabolism of oleic acid, a common fatty acid (see Fig. 17-10). Some spectacular examples of double-bond repositioning occur in the biosynthesis of cholesterol (see Fig. 21-37).

A two-part figure shows an isomerization reaction, the conversion of glucose 6-phosphate to fructose 6-phosphate, in part a and the role of an enediol intermediate in the reaction in part b. — FIGURE 13-6 Isomerization and elimination reactions. (a) The conversion of glucose 6-phosphate to fructose 6-phosphate, a reaction of sugar metabolism catalyzed by phosphohexose isomerase. (b) This reaction proceeds through an enediol intermediate. Light red screens follow the path of oxidation from left to right. $B^{1}$ $upper B Superscript 1$ and $B^{2}$ $upper B Superscript 2$ are ionizable groups on the enzyme; they are capable of donating and accepting protons (acting as general acids or general bases) as the reaction proceeds.

FIGURE 13-6 Isomerization and elimination reactions. (a) The conversion of glucose 6-phosphate to fructose 6-phosphate, a reaction of sugar metabolism catalyzed by phosphohexose isomerase. (b) This reaction proceeds through an enediol intermediate. Light red screens follow the path of oxidation from left to right. $B^{1}$ $upper B Superscript 1$ and $B^{2}$ $upper B Superscript 2$ are ionizable groups on the enzyme; they are capable of donating and accepting protons (acting as general acids or general bases) as the reaction proceeds.

Glucose 6-phosphate has C 1 and C 2 in a light red box that includes the atoms above and below them. C 1 is bonded to H to the left and double bonded to O below in the box; C 2 is bonded to H above and O H below in the box, C 3 is bonded to O H above and H below; C 4 and C 5 are each bonded to H above and O H below, and C 5 is bonded to H above and below and to O to the right that is further bonded to P bonded to O minus above and to the right and double bonded to O below. Right- and left-pointing arrows above blue highlighted phosphohexose isomerase show that this reaction yields fructose 6-phosphate. Fructose 6-phosphate has a similar structure except for the atoms within the light red box, in which C 1 is bonded to H above and O H below and C 2 is double bonded to O below. Part b shows four steps that occur during this reaction. C in a light red vertical box is double bonded to O below within the box, further bonded to the left, and bonded to C to the right that is bonded to H in a blue box above, bonded to O H below, and further bonded on the right. B superscript 1 with a red pair of electrons has a curved red arrow pointing to the H in a blue box. Step 1: B superscript 1 abstracts a proton. A curved red arrow points from the bond between H in the blue box and the bond between the two carbon atoms. Step 2: This allows the formation of a carbon to carbon double bond. A curved red arrow points from the double bond between C and O to H in a blue box below bonded to B superscript 2 and a curved red arrow points from the bond between the H in a blue box and B superscript 2 to B superscript 2. Step 3: Electrons from carbonyl form an O to H bond with the hydrogen ion donated by B superscript 2. An arrow points to an enediol intermediate in brackets to the right. It has C double bonded to C within a light red box with the left-hand C further bonded on the left and bonded to O below that is further bonded to H in a blue box and the right-hand C further bonded on the right and bonded below to O further bonded to H. A curved red arrow points from the double bond to H in a blue box above bonded to B superscript 1 and a red curved arrow points from the bond between this H in a blue box and B superscript 1 to B superscript 1. Step 5: An electron pair is displaced from the carbon to carbon bond to form a carbon to hydrogen bond with the proton donated by B superscript 1. A curved red arrow points from a red pair of electrons on B superscript 2 below to H bonded to O bonded to the right-hand C and from the bond between this H and O to the bond between this O and the right-hand C. Step 4: B superscript 2 abstracts a proton, allowing the formation of a C to O double bond. An arrow points right to show that this yields B superscript 1 with a red pair of electrons, B superscript 2 bonded to H, and a left-hand C that is further bonded on the left, bonded to H in a blue box above, bonded to O below bonded to H in a blue box, and bonded to C on the right in a light red box double bonded to O below in the light red box and further bonded on the right.

An example of an elimination reaction that does not affect overall oxidation state is the loss of water from an alcohol, resulting in the introduction of a $C ═ C$ $upper C box drawings double horizontal upper C$ bond:

R bonded to C bonded to H in a light red box above, H below, and C to the right bonded to H above, R superscript 1 to the right, and O H in a light red box below undergoes a reversible reaction. The forward reaction is accompanied by the loss of H 2 O in a light red box and the reverse reaction is accompanied by the addition of H 2 O. The product is C bonded to R to the upper left, bonded to H to the lower left, and double bonded to C to the right further bonded to H to the upper right and to R superscript 1 to the lower right.

Similar reactions can result from eliminations in amines.

Free-Radical Reactions

Once thought to be rare, the homolytic cleavage of covalent bonds to generate free radicals has now been found in a wide range of biochemical processes. These include isomerizations that make use of adenosylcobalamin $(vitamin B_{12})$ $left-parenthesis vitamin upper B Subscript 12 Baseline right-parenthesis$ or S-adenosylmethionine, which are initiated with a $5^{'}$ $5 prime$ -deoxyadenosyl radical (see the methylmalonyl-CoA mutase reaction in Box 17-2); certain radical-initiated decarboxylation reactions (Fig. 13-7); some reductase reactions, such as that catalyzed by ribonucleotide reductase (see Fig. 22-43); and some rearrangement reactions, such as that catalyzed by DNA photolyase (see Fig. 25-25).

A figure shows an example of a free radial-initiated decarboxylation reaction in which coproporphyrinogen Roman numeral 3 is converted to protoporphyrinogen Roman numeral 9. — FIGURE 13-7 A free radical–initiated decarboxylation reaction. The biosynthesis of heme in *Escherichia coli* includes a decarboxylation step in which propionyl side chains on the coproporphyrinogen III intermediate are converted to the vinyl side chains of protoporphyrinogen IX. When the bacteria are grown anaerobically the enzyme oxygen-independent coproporphyrinogen III oxidase, also called HemN protein, promotes decarboxylation via the free-radical mechanism shown here. The acceptor of the released electron is not known. For simplicity, only the relevant portions of the large coproporphyrinogen III and protoporphyrinogen molecules are shown; the entire structures are given in Figure 22-26. When *E. coli* is grown in the presence of oxygen, this reaction is an oxidative decarboxylation and is catalyzed by a different enzyme. [Information from G. Layer et al., *Curr. Opin. Chem. Biol.* 8:468, 2004, Fig. 4.]

Coproporphyrinogen Roman numeral 3 has a five-membered ring with double bonds at its upper right and lower left sides, N substituted for C at its lower right vertex and bonded to H, its upper right and lower left vertices bonded to R, its upper left vertex bonded to C H 3, and its top vertex connected by a blue bond to a three-carbon zigzag chain that has a blue bond to blue highlighted H from the carbon adjacent to the ring and that ends at C O O minus. X further bonded to the left with a single red dot has a curved red single-headed arrow to blue highlighted H and the blue bond between this H and C has two curved red single-headed arrows pointing in opposite directions, one toward H and one toward C. An arrow points right to show that this yields a coproporphyrinogenyl Roman numeral 3 radical, which has X bonded to blue highlighted H and a similar ring with a three-carbon chain in which the carbon adjacent to the ring has a single red dot and the bond between this carbon. A curved red single-headed arrow points from the red dot to the bond to its right, between the carbon adjacent to the ring and the middle carbon. A second curved red single-headed arrow points from the bond between the middle and terminal carbons of the chain to the bond between the carbon adjacent to the ring and the middle carbon. A right-pointing arrow has arrows leaving from it to show the loss of blue highlighted e minus and of blue highlighted C O 2. This yields protoporphyrinogen Roman numeral 9, which has a similar ring with a blue two-carbon chain attached to its top vertex that has a double bond between its two carbons.

Group Transfer Reactions

The transfer of acyl, glycosyl, and phosphoryl groups from one nucleophile to another is common in living cells. Acyl group transfer generally involves the addition of a nucleophile to the carbonyl carbon of an acyl group to form a tetrahedral intermediate:

A figure shows how a reactant is converted to a product through a tetrahedral intermediate.

The chymotrypsin reaction is one example of acyl group transfer (see Fig. 6-27). Glycosyl group transfers involve nucleophilic substitution at C-1 of a sugar ring, which is the central atom of an acetal. In principle, the substitution could proceed by an $S_{N} 1$ $upper S Subscript upper N Baseline 1$ or $S_{N} 2$ $upper S Subscript upper N Baseline 2$ pathway.

Phosphoryl group transfers play a special role in metabolic pathways, and these transfer reactions are discussed in detail in Section 13.3. A general theme in metabolism is the attachment of a good leaving group to a metabolic intermediate to “activate” the intermediate for subsequent reaction. Among the better leaving groups in nucleophilic substitution reactions are inorganic orthophosphate (the ionized form of $H_{3} {PO}_{4}$ $upper H Subscript 3 Baseline PO Subscript 4$ at neutral pH, a mixture of $H_{2} {PO}_{4}^{-}$ $upper H Subscript 2 Baseline PO Subscript 4 Superscript minus$ and ${HPO}_{4}^{2 -}$ $HPO Subscript 4 Superscript 2 minus$ , commonly abbreviated $P_{i}$ $upper P Subscript i$ ) and inorganic pyrophosphate ${(P}_{2} O_{7}^{4 -}$ $left-parenthesis upper P Subscript 2 Baseline upper O Subscript 7 Superscript 4 minus$ , abbreviated ${PP}_{i})$ $PP Subscript i Baseline right-parenthesis$ ; esters and anhydrides of phosphoric acid are effectively activated for reaction. Nucleophilic substitution is made more favorable by the attachment of a phosphoryl group to an otherwise poor leaving group such as $— OH$ $em-dash OH$ . Nucleophilic substitutions in which the phosphoryl group $(— {PO}_{3}^{2 -})$ $left-parenthesis em-dash PO Subscript 3 Superscript 2 minus Baseline right-parenthesis$ serves as a leaving group occur in hundreds of metabolic reactions.

Phosphorus can form five covalent bonds. The conventional representation of $P_{i}$ $upper P Subscript i$ (Fig. 13-8a), with three $P — O$ $upper P em-dash upper O$ bonds and one $P ═ O$ $upper P box drawings double horizontal upper O$ bond, is a convenient but inaccurate picture. In $P_{i}$ $upper P Subscript i$ , four equivalent phosphorus–oxygen bonds share some double-bond character, and the anion has a tetrahedral structure (Fig. 13-8b). Because oxygen is more electronegative than phosphorus, the sharing of electrons is unequal: the central phosphorus bears a partial positive charge and can therefore act as an electrophile. In a great many metabolic reactions, a phosphoryl group $(— {PO}_{3}^{2 -})$ $left-parenthesis em-dash PO Subscript 3 Superscript 2 minus Baseline right-parenthesis$ is transferred from ATP to an alcohol, forming a phosphate ester (Fig. 13-8c), or to a carboxylic acid, forming a mixed anhydride. When a nucleophile attacks the electrophilic phosphorus atom in ATP, a relatively stable pentacovalent structure forms as a reaction intermediate (Fig. 13-8d). With departure of the leaving group (ADP), the transfer of a phosphoryl group is complete. The large family of enzymes that catalyze phosphoryl group transfers with ATP as donor are called kinases (Greek kinein, “to move”). Hexokinase, for example, “moves” a phosphoryl group from ATP to the hexose glucose. Box 13-1 offers a primer on some of the broad classes of enzymes (including kinases) that you will encounter in your study of metabolism.

A four-part figure shows four examples of structures involved in phosphoryl group transfers with part a showing four resonance structures of phosphate, part b showing a more accurate representation of the resonance structures of phosphate, part c showing how the attack of a nucleophile on A T P displaces A D P, and part d showing the pentacovalent intermediate that transiently forms when a nucleophile attacks A T P and displaces A D P. — FIGURE 13-8 Phosphoryl group transfers: some of the participants. (a) In one (inadequate) representation of $P_{i}$ $upper P Subscript i$ , three oxygens are single-bonded to phosphorus, and the fourth is double-bonded, allowing the four different resonance structures shown here. (b) The resonance structures of $P_{i}$ $upper P Subscript i$ can be represented more accurately by showing all four phosphorus–oxygen bonds with some double-bond character; the hybrid orbitals so represented are arranged in a tetrahedron with P at its center. (c) When a nucleophile Z (in this case, the $— OH$ $em-dash OH$ on C-6 of glucose) attacks ATP, it displaces ADP (W). In this $S_{N} 2$ $upper S Subscript upper N Baseline 2$ reaction, a pentacovalent intermediate (d) forms transiently.

Part a shows four resonance structures of phosphate arranged as a square. At the upper left, P is bonded to O minus above, to the left, and below and double bonded to O to the right. It has a double-headed arrow to its right pointing to P bonded to O minus to the right, to the left, and below and double bonded to O above. This upper right-hand molecule has a double-headed arrow below pointing down to P bonded to O minus above, to the right, and below and double bonded to O on the left. This lower right-hand molecule has a double-headed arrow to its left pointing to P bonded to O minus above, to the right, and to the left and double bonded to O below. This lower left-hand molecule has a double-headed arrow pointing up to the starting molecule at the upper left side. Part b shows a structure in brackets with superscript 3 minus at the upper right. Within the brackets, P is hashed wedge bonded to O above and below and solid wedge bonded to O to the left and right. Dashed lines along the bonds form a cross-shape outlining the molecule. To the right, P is shown with four dashed lines to O atoms arranged in a tetrahedral around it: above, to the lower right, to the lower left, and to the left slightly below horizontal. Teardrop-shaped orbitals surround each bond between P and O and are wider around O and narrower where they come together near P. Solid lines connect the oxygen atoms, with O at the left connected by solid lines to O above, O to the far right and slightly down, and to the central O that is not as far to the right and slightly lower. This central O has a solid line connecting it to the O at the far right. The O at the far right also has a solid line to O at the top. Part c shows A T P as a rectangle labeled adenosine bonded to O bonded to P double bonded to O above, bonded to O minus below, and bonded to O on the right further bonded to P double bonded to O above, bonded to O minus below, and bonded to O on the right further bonded to P double bonded to O above and bonded to O minus to the right and below. Red highlighted glucose has H O bonded to R with a pair of electrons on O. A curved red arrow points from the pair of electrons to the right-hand P at the right end of the A T P molecule. Below, A D P is shown next to glucose 6-phosphate, a phosphate ester. A D P is shown as a rectangle labeled adenosine bonded to O on the right bonded to P double bonded to O above, bonded to O minus below, and bonded to O on the right further bonded to P double bonded to O above and bonded to O minus to the right and below. Glucose 6-phosphate, a phosphate ester, has P double bonded to O above, bonded to O minus to the left and below, and bonded to red highlighted O on the right connected by a red bond to red highlighted R. Part d shows a molecule with Z connected by a dashed line to a central P that is connected by a dashed line to W to its right, bonded to O below, solid wedge bonded to O to its upper left, and hashed wedge bonded to O to its upper right. Z equals R bonded to O H (nucleophile) and W equals A D P (leaving group).

Box 13-1

A Primer on Enzyme Names

The name kinase is applied to enzymes that transfer a phosphoryl group from a nucleoside triphosphate such as ATP to an acceptor molecule—a sugar (as in hexokinase and glucokinase), a protein (as in glycogen phosphorylase kinase), another nucleotide (as in nucleoside diphosphate kinase), or a metabolic intermediate such as oxaloacetate (as in PEP carboxykinase). The reaction catalyzed by a kinase is a phosphorylation. On the other hand, phosphorolysis is a displacement reaction in which phosphate is the attacking species and becomes covalently attached at the point of bond breakage. Such reactions are catalyzed by phosphorylases. Glycogen phosphorylase, for example, catalyzes the phosphorolysis of glycogen, producing glucose 1-phosphate. Dephosphorylation, the removal of a phosphoryl group from a phosphate ester, is catalyzed by phosphatases, with water as the attacking species. Fructose bisphosphatase-1 converts fructose 1,6-bisphosphate to fructose 6-phosphate in gluconeogenesis, and phosphorylase a phosphatase removes phosphoryl groups from phosphoserine in phosphorylated glycogen phosphorylase. Whew!

Citrate synthase, the first enzyme in the citric acid cycle (see Fig. 16-7), is one of many enzymes that catalyze condensation reactions, yielding a product more chemically complex than its precursors. Synthases catalyze condensation reactions in which no nucleoside triphosphate (ATP, GTP, and so forth) is required as an energy source. Synthetases catalyze condensations that do use ATP or another nucleoside triphosphate as a source of energy for the synthetic reaction. Succinyl-CoA synthetase is such an enzyme. Ligases (from the Latin ligare, “to tie together”) are enzymes that catalyze condensation reactions in which two atoms are joined, using ATP or another energy source. (Thus, synthetases are ligases.) DNA ligase, for example, closes breaks in DNA molecules, using energy supplied by either ATP or ${NAD}^{+}$ $NAD Superscript plus$ ; it is widely used in joining DNA pieces for genetic engineering. Ligases are not to be confused with lyases, enzymes that catalyze cleavages (or, in the reverse direction, additions) in which electronic rearrangements occur. The PDH complex, which oxidatively cleaves ${CO}_{2}$ $CO Subscript 2$ from pyruvate, is a member of the large class of lyases.

In some biological oxidation reactions, molecular oxygen is the electron acceptor. If the oxygen atoms do not appear in the oxidized product, the enzyme is an oxidase. If one or both of the oxygen atoms do appear in the oxidized product, as a new hydroxyl or carboxyl group, for example, the enzyme is an oxygenase. Both classes are further subdivided. Mixed-function oxidases oxidize two different substrates simultaneously. Monooxygenases and dioxygenases catalyze reactions in which one or two oxygen atoms, respectively, are incorporated into the organic product. These enzymes are particularly important in biosynthetic pathways of fatty acids and eicosanoids (see Box 21-1). Dehydrogenases catalyze oxidation-reductase reactions in which ${NAD}^{+}$ $NAD Superscript plus$ is electron acceptor, and molecular oxygen is generally not involved.

Unfortunately, these descriptions of enzyme types overlap, and many enzymes have two or more common names. Succinyl-CoA synthetase, for example, is also called succinate thiokinase; the enzyme is both a synthetase in the citric acid cycle and a kinase when acting in the direction of succinyl-CoA synthesis. This raises another source of confusion in the naming of enzymes. An enzyme may have been discovered by the use of an assay in which, say, A is converted to B. The enzyme is then named for that reaction. Later work may show, however, that in the cell, the enzyme functions primarily in converting B to A. Commonly, the first name continues to be used, although the metabolic role of the enzyme would be better described by naming it for the reverse reaction. The glycolytic enzyme pyruvate kinase illustrates this situation (p. 521). To a beginner in biochemistry, this duplication in nomenclature can be bewildering. International committees have made heroic efforts to systematize the nomenclature of enzymes (see Table 6-3 for a brief summary of the system), but some systematic names have proved too long and cumbersome and are not frequently used in biochemical conversation.

We have tried throughout this book to use the enzyme name most commonly employed by working biochemists and to point out cases in which an enzyme has more than one widely used name.

Phosphoryl groups are not the only groups that activate molecules for reaction. Thioalcohols (thiols), in which the oxygen atom of an alcohol is replaced with a sulfur atom, are also good leaving groups. Thiols activate carboxylic acids by forming thioesters (thiol esters). In later chapters we discuss several reactions, including those catalyzed by the fatty acyl synthases in lipid synthesis (see Fig. 21-2), in which nucleophilic substitution at the carbonyl carbon of a thioester results in transfer of the acyl group to another moiety.

Oxidation-Reduction Reactions

We will encounter carbon atoms in five oxidation states, depending on the elements with which they share electrons (Fig. 13-9), and transitions between these states are of crucial importance in metabolism (oxidation-reduction reactions are the topic of Section 13.4). In many biological oxidations, a compound loses two electrons and two hydrogen ions (that is, two hydrogen atoms); these reactions are commonly called dehydrogenations, and the enzymes that catalyze them are called dehydrogenases (Fig. 13-10). In some, but not all, biological oxidations, a carbon atom becomes covalently bonded to an oxygen atom. The enzymes that catalyze oxidations with oxygen as electron acceptor are generally called oxidases or, if the oxygen atom is derived directly from molecular oxygen $(O_{2})$ $left-parenthesis upper O Subscript 2 Baseline right-parenthesis$ and incorporated into the product, oxygenases.

A figure shows oxidation levels of carbon in five biomolecules: an alkane, an alcohol, an aldehyde (ketone), a carboxylic acid, and carbon dioxide. — FIGURE 13-9 The oxidation levels of carbon in biomolecules. Each compound is formed by oxidation of the carbon shown in red in the compound immediately above. Carbon dioxide is the most highly oxidized form of carbon found in living systems.

A figure shows an oxidation-reduction reaction in which lactate is converted to pyruvate. — FIGURE 13-10 An oxidation-reduction reaction. Shown here is the oxidation of lactate to pyruvate. In this dehydrogenation, two electrons and two hydrogen ions (the equivalent of two hydrogen atoms) are removed from C-2 of lactate, an alcohol, to form pyruvate, a ketone. In cells the reaction is catalyzed by lactate dehydrogenase and the electrons are transferred to the cofactor nicotinamide adenine dinucleotide $({NAD}^{+})$ $left-parenthesis NAD Superscript plus Baseline right-parenthesis$ . This reaction is fully reversible; pyruvate can be reduced by electrons transferred from the cofactor.

FIGURE 13-10 An oxidation-reduction reaction. Shown here is the oxidation of lactate to pyruvate. In this dehydrogenation, two electrons and two hydrogen ions (the equivalent of two hydrogen atoms) are removed from C-2 of lactate, an alcohol, to form pyruvate, a ketone. In cells the reaction is catalyzed by lactate dehydrogenase and the electrons are transferred to the cofactor nicotinamide adenine dinucleotide $({NAD}^{+})$ $left-parenthesis NAD Superscript plus Baseline right-parenthesis$ . This reaction is fully reversible; pyruvate can be reduced by electrons transferred from the cofactor.

Every oxidation must be accompanied by a reduction, in which an electron acceptor acquires the electrons removed by oxidation. Oxidation reactions generally release energy (think of campfires: the compounds in wood are oxidized by oxygen molecules in the air). Most living cells obtain the energy needed for cellular work by oxidizing metabolic fuels such as carbohydrates or fat (photosynthetic organisms can also trap and use the energy of sunlight). The catabolic (energy-yielding) pathways described in Chapters 14 through 19 are oxidative reaction sequences that result in the transfer of electrons from fuel molecules, through a series of electron carriers, to oxygen. The high affinity of $O_{2}$ $upper O Subscript 2$ for electrons makes the overall electron-transfer process highly exergonic, providing the energy that drives ATP synthesis — the central goal of catabolism.

Many of the reactions within these five classes are facilitated by cofactors, in the form of coenzymes and metal ions ( $vitamin B_{12}$ $vitamin upper B Subscript 12 Baseline$ , S-adenosylmethionine, folate, nicotinamide, and ${Fe}^{2 +}$ $Fe Superscript 2 plus$ are some examples). Cofactors bind to enzymes — in some cases reversibly, in other cases almost irreversibly — and give them the capacity to promote a particular kind of chemistry (p. 178). Most cofactors participate in a narrow range of closely related reactions. In the following chapters, we introduce and discuss each important cofactor at the point where we first encounter its function. The cofactors provide another way to organize the study of biochemical processes, given that the reactions facilitated by a given cofactor generally are mechanistically related.

Biochemical and Chemical Equations Are Not Identical

Biochemists write metabolic equations in a simplified way, and this is particularly evident for reactions involving ATP. Phosphorylated compounds can exist in several ionization states and, as we have noted, the different species can bind ${Mg}^{2 +}$ $Mg Superscript 2 plus$ . For example, at pH 7 and 2 mm ${Mg}^{2 +}$ $Mg Superscript 2 plus$ , ATP exists as an equilibrium distribution of the forms ${ATP}^{4 -}$ $ATP Superscript 4 minus$ , ${HATP}^{3 -}$ $HATP Superscript 3 minus$ , $H_{2} {ATP}^{2 -}$ $upper H Subscript 2 Baseline ATP Superscript 2 minus$ , ${MgHATP}^{-}$ $MgHATP Superscript minus$ , and ${Mg}_{2} ATP$ $Mg Subscript 2 Baseline ATP$ . In thinking about the biological role of ATP, however, we are not always interested in all this detail, and so we consider ATP as an entity made up of a sum of species, and we write its hydrolysis as the biochemical equation

ATP + H_{2} O \overset{}{\to} ADP + P_{i}

$ATP plus upper H Subscript 2 Baseline upper O right-arrow Overscript Endscripts ADP plus upper P Subscript i Baseline$

where ATP, ADP, and $P_{i}$ $upper P Subscript i$ are sums of species. The corresponding standard transformed equilibrium constant, $K_{eq}^{'} = {[ADP]}_{eq} {[P_{i}]}_{eq} / {[ATP]}_{eq}$ $upper K prime Subscript eq Baseline equals left-bracket ADP right-bracket Subscript eq Baseline left-bracket upper P Subscript i Baseline right-bracket Subscript eq Baseline slash left-bracket ATP right-bracket Subscript eq Baseline$ , depends on the pH and the concentration of free ${Mg}^{2 +}$ $Mg Superscript 2 plus$ . Note that $H^{+}$ $upper H Superscript plus$ and ${Mg}^{2 +}$ $Mg Superscript 2 plus$ do not appear in the biochemical equation, because their concentrations are not significantly changed by the reaction. Thus a biochemical equation does not necessarily balance H, Mg, or charge, although it does balance all other elements involved in the reaction (C, N, O, and P in the equation above).

We can write a chemical equation that does balance for all elements and for charge. For example, when ATP is hydrolyzed at a pH above 8.5 in the absence of ${Mg}^{2 +}$ $Mg Superscript 2 plus$ , the chemical reaction is represented by

{ATP}^{4 -} + H_{2} O \overset{}{\to} {ADP}^{3 -} + {HPO}_{4}^{2 -} + H^{+}

$ATP Superscript 4 minus Baseline plus upper H Subscript 2 Baseline upper O right-arrow Overscript Endscripts ADP Superscript 3 minus Baseline plus HPO Subscript 4 Superscript 2 minus Baseline plus upper H Superscript plus$

The corresponding equilibrium constant,

K_{eq} = {[{ADP}^{3 -}]}_{eq} {[{HPO}_{4}^{2 -}]}_{eq} {[H^{+}]}_{eq} / {[{ATP}^{4 -}]}_{eq},

$upper K Subscript eq Baseline equals left-bracket ADP Superscript 3 minus Baseline right-bracket Subscript eq Baseline left-bracket HPO Subscript 4 Superscript 2 minus Baseline right-bracket Subscript eq Baseline left-bracket upper H Superscript plus Baseline right-bracket Subscript eq Baseline slash left-bracket ATP Superscript 4 minus Baseline right-bracket Subscript eq Baseline comma$

depends only on temperature, pressure, and ionic strength.

Both ways of writing a metabolic reaction have value in biochemistry. Chemical equations are needed when we want to account for all atoms and charges in a reaction, as when we are considering the mechanism of a chemical reaction. Biochemical equations are used to determine in which direction a reaction will proceed spontaneously, given a specified pH and $[{Mg}^{2 +}]$ $left-bracket Mg Superscript 2 plus Baseline right-bracket$ , or to calculate the equilibrium constant of such a reaction.

Throughout this book we use biochemical equations, unless the focus is on chemical mechanism, and we use values of $Δ G^{'} °$ $upper Delta upper G prime degree$ and $K_{eq}^{'}$ $upper K prime Subscript eq$ as determined at pH 7 and 1 mm ${Mg}^{2 +}$ $Mg Superscript 2 plus$ .

SUMMARY 13.2 Chemical Logic and Common Biochemical Reactions

Living systems make use of a large number of chemical reactions that can be classified into five general types: reactions that make or break carbon–carbon bonds; internal rearrangements and eliminations; free-radical reactions; group transfers; and oxidation-reduction reactions. Heterolytic cleavages occur often in reactions that make or break $C — C$ $upper C em-dash upper C$ bonds.
Carbonyl groups play a special role in reactions that form or cleave $C — C$ $upper C em-dash upper C$ bonds. Carbanion intermediates are common and are stabilized by adjacent carbonyl groups or, less often, by imines or certain cofactors.
A redistribution of electrons can produce internal rearrangements, isomerizations, and eliminations. Such reactions include intramolecular oxidation-reduction, change in cis-trans arrangement at a double bond, and transposition of double bonds.
Homolytic cleavage of covalent bonds to generate free radicals occurs in some pathways.
Phosphoryl transfer reactions are an especially important type of group transfer in cells, required for the activation of molecules for reactions that would otherwise be highly unfavorable.
Oxidation-reduction reactions involve the loss or gain of electrons: one reactant gains electrons and is reduced, while the other loses electrons and is oxidized. Oxidation reactions generally release energy and are important in catabolism.
Biochemists often write reaction equations that are not balanced for $H^{+}$ $upper H Superscript plus$ and don’t attempt to describe the state of phosphate ionization.