Glyceraldehyde 3-phosphate -

FIGURE 29.11 Mechanism of step 4 in FIGURE 29.8, the cleavage of fructose 1,6-bisphosphate to yield glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. The reaction occurs through an iminium ion formed by reaction with a lysine residue in the enzyme.


Glyceraldehyde 3-phosphate -

Step 5 of FIGURE 29.8: Isomerization
Dihydroxyacetone phosphate is isomerized in step 5 by triose phosphate isomerase to form a second equivalent of glyceraldehyde 3-phosphate. As in the conversion of glucose 6-phosphate to fructose 6-phosphate in step 2, the isomerization takes place by keto-enol tautomerization through a common enediol intermediate. A base deprotonates C 1 and then reprotonates C2 using the same hydrogen. The net result of steps 4 and 5 together is the production of two glyceraldehyde 3-phosphate molecules, both of which pass down the rest of the pathway. Thus, each of the remaining five steps of glycolysis takes place twice for every glucose molecule entering at step 1.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-1058.jpg?height=329&width=1291&top_left_y=193&top_left_x=417)


Steps 6-7 of FIGURE 29.9: Oxidation, Phosphorylation, and Dephosphorylation -

Glyceraldehyde 3-phosphate is oxidized and phosphorylated in step 6 to give 1,3-bisphosphoglycerate (FIGURE 29.12). The reaction is catalyzed by glyceraldehyde 3-phosphate dehydrogenase and begins by nucleophilic addition of the -SH group of a cysteine residue in the enzyme to the aldehyde carbonyl group to yield a hemithioacetal (Section 19.10), the sulfur analog of a hemiacetal. Oxidation of the hemithioacetal -OH group by $\mathrm{NAD}^{+}$then yields a thioester, which reacts with phosphate ion in a nucleophilic acyl substitution step to yield 1,3-bisphosphoglycerate, a mixed anhydride derived from a carboxylic acid and a phosphoric acid.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-1058.jpg?height=803&width=1586&top_left_y=864&top_left_x=264)

FIGURE 29.12 Mechanism of step 6 in FIGURE 29.9, the oxidation and phosphorylation of glyceraldehyde 3-phosphate to give 1,3-bisphosphoglycerate. The process occurs through initial formation of a hemiacetal that is oxidized to a thioester and converted into an acyl phosphate.
Like all anhydrides (Section 21.5), the mixed carboxylic-phosphoric anhydride is a reactive substrate in nucleophilic acyl (or phosphoryl) substitution reactions. Reaction of 1,3-bisphosphoglycerate with ADP occurs in step 7 by substitution on phosphorus, resulting in transfer of a phosphate group to ADP and giving ATP plus 3-phosphoglycerate. The process is catalyzed by phosphoglycerate kinase and requires $\mathrm{Mg}^{2+}$ as cofactor. Together, steps 6 and 7 accomplish the oxidation of an aldehyde to a carboxylic acid.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-1058.jpg?height=416&width=1353&top_left_y=2009&top_left_x=386)


Step 8 of FIGURE 29.9: Isomerization
3-Phosphoglycerate isomerizes to 2-phosphoglycerate in a step catalyzed by phosphoglycerate mutase. In
plants, 3-phosphoglycerate transfers its phosphoryl group from its C3 oxygen to a histidine residue on the enzyme in one step and then accepts the same phosphoryl group back onto the C2 oxygen in a second step. In animals and yeast, however, the enzyme contains a phosphorylated histidine, which transfers its phosphoryl group to the C2 oxygen of 3-phosphoglycerate and forms 2,3-bisphosphoglycerate as intermediate. The same histidine then accepts a phosphoryl group from the C3 oxygen to yield the isomerized product plus the regenerated enzyme. As explained in Section 29.4, we'll occasionally use an abbreviated mechanism for nucleophilic acyl substitution reactions to save space.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-1059.jpg?height=592&width=1464&top_left_y=517&top_left_x=325)


Steps 9-10 of FIGURE 29.9: Dehydration and Dephosphorylation
Like most $\beta$-hydroxy carbonyl compounds, 2-phosphoglycerate undergoes a ready dehydration in step 9 by an E 1 cB mechanism (Section 23.3). The process is catalyzed by enolase, and the product is phosphoenolpyruvate, abbreviated PEP. Two $\mathrm{Mg}^{2+}$ ions are associated with the 2-phosphoglycerate to neutralize the negative charges.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-1059.jpg?height=372&width=1147&top_left_y=1305&top_left_x=489)


Transfer of the phosphoryl group to ADP in step 10 then generates ATP and gives enolpyruvate, which tautomerizes to pyruvate. The reaction is catalyzed by pyruvate kinase and requires that a molecule of fructose 1,6-bisphosphate also be present, as well as 2 equivalents of $\mathrm{Mg}^{2+}$. One $\mathrm{Mg}^{2+}$ ion coordinates to ADP, and the other increases the acidity of a water molecule necessary for protonation of the enolate ion.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-1059.jpg?height=376&width=1206&top_left_y=1858&top_left_x=457)


The overall result of glycolysis can be summarized by the following equation:
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-1060.jpg?height=212&width=1007&top_left_y=192&top_left_x=559)


Glucose


PROBLEM Identify the two steps of glycolysis in which ATP is produced. 29-7


PROBLEM Look at the entire glycolysis pathway, and make a list of the kinds of organic reactions that take 29-8 place-nucleophilic acyl substitutions, aldol reactions, E1cB reactions, and so forth.


Steps 6-7 of FIGURE 29.9: Oxidation, Phosphorylation, and Dephosphorylation - 29.6 Conversion of Pyruvate to Acetyl CoA

Pyruvate, produced by catabolism of glucose (and by degradation of several amino acids), can undergo several further transformations depending on the conditions and on the organism. In the absence of oxygen, pyruvate can either be reduced by NADH to yield lactate $\left[\mathrm{CH}_{3} \mathrm{CH}(\mathrm{OH}) \mathrm{CO}_{2}{ }^{-}\right.$] or, in yeast, fermented to give ethanol. Under typical aerobic conditions in mammals, however, pyruvate is converted by a process called oxidative decarboxylation to give acetyl CoA plus $\mathrm{CO}_{2}$. (Oxidative because the oxidation state of the carbonyl carbon rises from that of a ketone to that of a thioester.)


The conversion occurs through a multistep sequence of reactions catalyzed by a complex of enzymes and cofactors called the pyruvate dehydrogenase complex. The process occurs in three stages, each catalyzed by one of the enzymes in the complex, as outlined in FIGURE 29.13. Acetyl CoA, the ultimate product, then acts as fuel for the final stage of catabolism, the citric acid cycle.


Step 1 of FIGURE 29.13: Addition of Thiamin Diphosphate
The conversion of pyruvate to acetyl CoA begins by reaction of pyruvate with thiamin diphosphate, a derivative of vitamin $B_{1}$. Formerly called thiamin pyrophosphate, thiamin diphosphate is usually abbreviated as TPP. The spelling thiamine is also correct and frequently used.


The key structural element in thiamin diphosphate is the thiazolium ring-a five-membered, unsaturated heterocycle containing a sulfur atom and a positively charged nitrogen atom. The thiazolium ring is weakly acidic, with a $\mathrm{p} K_{\mathrm{a}}$ of approximately 18 for the ring hydrogen between N and S . Bases can therefore deprotonate thiamin diphosphate, leading to formation of an ylide much like the phosphonium ylides used in Wittig reactions (Section 19.11). As in the Wittig reaction, the TPP ylide is a nucleophile and adds to the ketone carbonyl group of pyruvate to yield an alcohol addition product.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-1061.jpg?height=516&width=1299&top_left_y=195&top_left_x=413)
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$$
\text { Pyruvate } \begin{gathered}
\text { Thiamin } \\
\text { diphosphate } \\
\text { ylide }
\end{gathered}
$$


FIGURE 29.13 MECHANISM -

Mechanism for the conversion of pyruvate to acetyl CoA through a multistep sequence of reactions that requires three different enzymes and four different coenzymes. The individual steps are explained in the text.
(1) Nucleophilic addition of thiamin diphosphate (TPP) ylide to pyruvate gives an alcohol addition product.


FIGURE 29.13 MECHANISM -

Decarboxylation occurs in a step analogous to the loss of $\mathrm{CO}_{2}$ from a $\beta$-keto acid, yielding the enamine hydroxyethylthiamin diphosphate (HETPP).
(3) The enamine double bond attacks a sulfur atom of lipoamide and carries out an $\mathrm{S}_{\mathrm{N}}{ }^{2-}$ like displacement of the second sulfur to yield a hemithioacetal.
(4) Elimination of thiamin diphosphate ylide from the hemithioacetal intermediate yields acetyl dihydrolipoamide . . .
5. . . which reacts with coenzyme A in a nucleophilic acyl substitution reaction to exchange one thioester for another and give acetyl CoA plus dihydrolipoamide.
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Acetyl CoA
$+$
<img class="imgSvg" id = "m6sn3qbeguleo9re67t" 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FIGURE 29.13 MECHANISM -

Dihydrolipoamide


FIGURE 29.13 MECHANISM -

Step 2 of FIGURE 29.13: Decarboxylation
The TPP addition product, which contains an iminium ion $\beta$ to a carboxylate anion, undergoes decarboxylation in much the same way that a $\beta$-keto acid decarboxylates in the acetoacetic ester synthesis (Section 22.7). The $\mathrm{C}=\mathrm{N}^{+}$bond of the pyruvate addition product acts like the $\mathrm{C}=\mathrm{O}$ bond of a $\beta$-keto acid to accept electrons as $\mathrm{CO}_{2}$ leaves, giving hydroxyethylthiamin diphosphate (HETPP).
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-1063.jpg?height=313&width=939&top_left_y=429&top_left_x=596)


FIGURE 29.13 MECHANISM -

Step 3 of FIGURE 29.13: Reaction with Lipoamide
Hydroxyethylthiamin diphosphate is an enamine $\left(\mathrm{R}_{2} \mathrm{~N}-\mathrm{C}=\mathrm{C}\right)$, which, like all enamines, is nucleophilic (Section 23.11). It therefore reacts with the enzyme-bound disulfide lipoamide by nucleophilic attack on a sulfur atom, displacing the second sulfur in an $\mathrm{S}_{\mathrm{N}} 2$-like process.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-1063.jpg?height=416&width=974&top_left_y=952&top_left_x=581)
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-1063.jpg?height=352&width=936&top_left_y=1404&top_left_x=578)

Step 4 of FIGURE 29.13: Elimination of Thiamin Diphosphate
The product of the HETPP reaction with lipoamide is a hemithioacetal, which eliminates thiamin diphosphate ylide. This elimination is the reverse of the ketone addition in step 1 and generates acetyl dihydrolipoamide.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-1063.jpg?height=323&width=1147&top_left_y=1931&top_left_x=489)

Step 5 of FIGURE 29.13: Acyl Transfer
Acetyl dihydrolipoamide, a thioester, undergoes a nucleophilic acyl substitution reaction with coenzyme A to yield acetyl CoA plus dihydrolipoamide. The dihydrolipoamide is then oxidized back to lipoamide by FAD (Section 29.3), and the $\mathrm{FADH}_{2}$ that results is in turn oxidized back to FAD by $\mathrm{NAD}^{+}$, completing the catalytic cycle.
![](https://cdn.mathpix.com/cropped/2025_02_06_5556f7656cbdcaa0f9a7g-1064.jpg?height=868&width=1383&top_left_y=187&top_left_x=371)


FIGURE 29.13 MECHANISM -

PROBLEM Which carbon atoms in glucose end up as $-\mathrm{CH}_{3}$ carbons in acetyl CoA? Which carbons end up as 29-9 $\mathrm{CO}_{2}$ ?


FIGURE 29.13 MECHANISM - 29.7 The Citric Acid Cycle

The initial stages of catabolism result in the conversion of both fats and carbohydrates into acetyl groups that are bonded through a thioester link to coenzyme A. Acetyl CoA then enters the next stage of catabolism-the citric acid cycle, also called the tricarboxylic acid (TCA) cycle, or Krebs cycle, after Hans Krebs, who unraveled its complexities in 1937. The overall result of the cycle is the conversion of an acetyl group into two molecules of $\mathrm{CO}_{2}$ plus reduced coenzymes by the eight-step reaction sequence shown in FIGURE 29.14.


As its name implies, the citric acid cycle is a closed loop of reactions in which the product of the final step (oxaloacetate) is a reactant in the first step. The intermediates are constantly regenerated, flowing continuously through the cycle, which operates as long as the oxidizing coenzymes $\mathrm{NAD}^{+}$and FAD are available. To meet this condition, the reduced coenzymes NADH and $\mathrm{FADH}_{2}$ must be reoxidized via the electron-transport chain, which in turn relies on oxygen as the ultimate electron acceptor. Thus, the cycle is dependent on the availability of oxygen and on the operation of the electron-transport chain.


FIGURE 29.14 MECHANISM