Oxidative decarboxylation, pyruvate steps

Pyruvate produced by glycolysis is a significant source of acetyl-CoA for the TCA cycle. Because, in eukaryotic ceils, glycolysis occurs in the cytoplasm, whereas the TCA cycle reactions and ail subsequent steps of aerobic metabolism take place in the mitochondria, pyruvate must first enter the mitochondria to enter the TCA cycle. The oxidative decarboxylation of pyruvate to acetyl-CoA,... 

Step 4 of Figure 29.12 Oxidative Decarboxylation The transformation of cr-ketoglutarate to succinyl CoA in step 4 is a multistep process just like the transformation of pyruvate to acetyl CoA that we saw in Figure 29.11. In both cases, an -keto acid loses C02 and is oxidized to a thioester in a series of steps catalyzed by a multienzynie dehydrogenase complex. As in the conversion of pyruvate to acetyl CoA, the reaction involves an initial nucleophilic addition reaction to a-ketoglutarate by thiamin diphosphate vlide, followed by decarboxylation, reaction with lipoamide, elimination of TPP vlide, and finally a transesterification of the dihydrolipoamide thioester with coenzyme A. 

Summarizing the results obtained by controlled potential electrolysis and polarography, the reaction process for the electrolytic evolution of CO2 was estimated to be as follows the first step was one electron transfer from DMFC in NB to FMN in W as in Eq. (7). The second step was the catalytic reduction of O2 by FMNH as in Eq. (8). The final step was the oxidation of pyruvic acid by the reduction product of O2, H2O2, in W as in Eq. (9), well-known as an oxidative decarboxylation of a-keto acids [43] ... 

SOME STEPS IN THE TRICARBOXYLIC ACID CYCLE Oxidative Decarboxylation of Pyruvate The Intracellular Function of Vitamin Bj... 

In the first step, pyruvate is decarboxylated in an irreversible reaction catalyzed by pyruvate decarboxylase. This reaction is a simple decarboxylation and does not involve the net oxidation of pyruvate. Pyruvate decarboxylase requires Mg24" and has a tightly bound coenzyme, thiamine pyrophosphate, discussed below. In the second step, acetaldehyde is reduced to ethanol through the action of alcohol dehydrogenase, with... 

Figure 16-6 shows schematically how the pyruvate dehydrogenase complex carries out the five consecutive reactions in the decarboxylation and dehydrogenation of pyruvate. Step CD is essentially identical to the reaction catalyzed by pyruvate decarboxylase (see Fig. 14-13c) C-l of pyruvate is released as C02, and C-2, which in pyruvate has the oxidation state of an aldehyde, is attached to TPP as a hydroxyethyl group. This first step is the slowest and therefore limits the rate of the overall reaction. It is also the point at which the PDH complex exercises its substrate specificity. In step (2) the hydroxyethyl group is oxidized to the level of a car-...

There is an alternative route, called the pentose phosphate pathway, by which glucose enters the glycolytic sequence to pyruvate. This route achieves the oxidative decarboxylation of glucose to give ribose, as the 5-phosphate ester. The essential steps are... 

Reactions of the Pyruvate Dehydrogenase Complex Two of the steps in the oxidative decarboxylation of pyruvate (steps 0 and in Fig. 16-6) do not involve any of the three carbons of pyruvate yet are essential to the operation of the PDH complex. Explain. 

Diacetyl, and its reduction products, acetoin and 2,3-butanediol, are also derived from acetaldehyde (Fig 8D.7), providing additional NADH oxidation steps. Diacetyl, which is formed by the decarboxylation of a-acetolactate, is regulated by valine and threonine availability (Dufour 1989). When assimilable nitrogen is low, valine synthesis is activated. This leads to the formation of a-acetolactate, which can be then transformed into diacetyl via spontaneous oxidative decarboxylation. Because valine uptake is suppressed by threonine, sufficient nitrogen availability represses the formation of diacetyl. Moreover, the final concentration of diacetyl is determined by its possible stepwise reduction to acetoin and 2,3-butanediol, both steps being dependent on NADH availability. Branched-chain aldehydes are formed via the Ehrlich pathway (Fig 8D.7) from precursors formed by combination of acetaldehyde with pyruvic acid and a-ketobutyrate (Fig 8D.7). 

In contrast to the diversity of pathways leading from glucose to pyruvate, there is a distinct unity in the way archaebacteria oxidatively decarboxylate this C3-acid to acetyl-CoA. Not only that, but the comparison of the enzymology of this step with the analogous reaction in eubacteria and eukaryotes provides interesting parallels and differences [1]. 

Thiamine pyrophosphate has two important coenzyme roles, both of which focus mostly on carbohydrate metabolism (Figs. 8.26 and 8.27). The active portion of the coen- rae is the thiazole ring. The first step in the oxidative decarboxylation of a-keto acids requires TPP. The two most common examples are pyruvate and a-ketoglutarate, oxidatively decarboxyatedto acetyl CoA and succinyl CoA, respectively. The same reaction is found in the metabolism of the branched-chain amino acids valine, isoleucine, leucine, and methionine. In all cases, TPP is a coenzyme in a mitochondrial multienzyme complex, consisting of TPP, lipoic acid, coenzyme A, FAD, and NAD. Note the number of vitamins required for the oxidative decarboxylation of a-keto acids thiamine (TPP), pantothenic acid (coenzyme A), riboflavin (FAD),and niacin (NAD). 

As stated earlier, glucose can be formed from pyruvate (Section 16.3). However, the formation of acetyl CoAfrom pyruvate is an irreversible step in animals and thus they are unable to convert acetyl Co A back into glucose. The oxidative decarboxylation of pyruvate to acetyl CoA commits the carbon atoms of glucose to two principal fates oxidation to CO2 by the citric acid... 

A third fate of pyruvate is its carboxylation to oxaloacetate inside mitochondria, the first step in gluconeogenesis. This reaction and the subsequent conversion of oxaloacetate into phosphoenol pyruvate bypass an irreversible step of glycolysis and hence enable glucose to he synthesized from pyruvate. The carboxylation of pyruvate is also important for replenishing intermediates of the citric acid cycle. Acetyl CoA activates pyruvate carboxylase, enhancing the synthesis of oxaloacetate, when the citric acid cycle is slowed by a paucity of this intermediate. A fourth fate of pyruvate is its oxidative decarboxylation to acetyl CoA, as described on page 763. 

The first step in the reaction sequence is the removal of carbon dioxide from pyruvic acid, and its simultaneous oxidation, in a reaction described as oxidative decarboxylation. This could be written... 

Valine, leucine, and isoleucine - The synthetic pathway from threonine and pyruvate to valine, leucine and isoleucine is outlined in Figure 21.26. The last four reactions in the biosynthesis of valine and isoleucine are catalyzed by the same four enzymes. Threonine dehydratase, which catalyzes the first step in conversion of threonine to isoleucine, is inhibited by isoleucine. Leucine, isoleucine, and valine are all catabolized via transamination followed by oxidative decarboxylation of the respective keto-acids (see here) and oxidation. The oxidation is similar to fatty acid oxidation, except for a debranching reaction for each intermediate. 

---