Pyruvate dehydrogenase coenzyme effect

As shown in Fig. 7, the first step involved in the decarboxylation of an alpha-keto acid by thiamine pyrophosphate is the addition of the carbonyl by the carbanion nucleophile, followed by decarboxylation of the acid. As reviewed by Jencks (1975), investigations of the role of thiamine pyrophosphate analogs in the pyruvate dehydrogenase-catalyzed decarboxylation of pyruvate have provided evidence for rate enhancement by a desolvation effect. This effect comes about because of the removal of both the carboxylate group of the substrate and the cationic nitrogen of the coenzyme from an aqueous environment to the hydrophobic active site of the enzyme. The bulky and apparently chemically nonfunctional pyrophosphate and pyrimidine moieties of the... 

Now this reaction is effectively a repeat of the pyruvate acetyl-CoA oxidative decarboxylation we saw at the beginning of the Krebs cycle. It similarly requires thiamine diphosphate, lipoic acid, coenzyme A and NAD+. A further feature in common with that reaction is that 2-oxoglutarate dehydrogenase is also an enzyme complex comprised of three separate enzyme activities. 2-Oxoglutarate is thus transformed into succinyl-CoA, with the loss of... 

Figure 22.5 An example of reactions involved in an enzyme-catalyzed recycling processes for amplification of the sensitivity. In the left part (A) of the figure the enzyme-pair hexokinase and pyruvate kinase is used for recycling of the coenzyme ATP/ADP. In the right part (B), substrate recycling of pymvate or lactate is accomplished using the enzyme-pair lactate oxidase/lactate dehydrogenase. A multiplication effect is obtained by combination of A and B resulting in a very high sensitivity [27], The calorimetric sensitivity is further inreased by including catalase (cat).

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