2-Oxoglutarate dehydrogenase complex reaction

The intermediary metabolism has multienzyme complexes which, in a complex reaction, catalyze the oxidative decarboxylation of 2-oxoacids and the transfer to coenzyme A of the acyl residue produced. NAD" acts as the electron acceptor. In addition, thiamine diphosphate, lipoamide, and FAD are also involved in the reaction. The oxoacid dehydrogenases include a) the pyruvate dehydrogenase complex (PDH, pyruvate acetyl CoA), b) the 2-oxoglutarate dehydrogenase complex of the tricarboxylic acid cycle (ODH, 2-oxoglutarate succinyl CoA), and c) the branched chain dehydrogenase complex, which is involved in the catabolism of valine, leucine, and isoleucine (see p. 414). 

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... 

There are two 2-oxoacid dehydrogenase multienzyme complexes in E. coli. One is specific for pyruvate, the other for 2-oxoglutarate. Each complex is about the size of a ribosome, about 300 A across. The pyruvate dehydrogenase is composed of three types of polypeptide chains El, the pyruvate decarboxylase (an a2 dimer of Mr — 2 X 100 000) E2, lipoate acetyltransferase (Mr = 80 000) and E3, lipoamide dehydrogenase (an a2 dimer of Mr = 2 X 56 000). These catalyze the oxidative decarboxylation of pyruvate via reactions 1.6, 1.7, and 1.8. (The relevant chemistry of the reactions of thiamine pyrophosphate [TPP], hydroxyethylthiamine pyrophosphate [HETPPJ, and lipoic acid [lip-S2] is discussed in detail in Chapter 2, section C3.)... 

The reaction of the pyruvate dehydrogenase complex is shown in Figure 6.2 the reactions of the 2-oxoglutarate and branched-chain oxo-acid dehydrogenase complexes follow the same sequence, and the multienzyme complexes are similar. 

Important sites of inhibition are the pyruvate dehydrogenase complex, which converts pyruvate into acetyl-CoA isocitrate dehydrogenase, which converts isocitrate into 2-oxoglutarate and 2-oxoglutarate dehydrogenase. The enzyme citrate synthase, which catalyzes the first reaction of the cycle, is also inhibited by ATP. ... 

This decarboxylation reaction unlike reaction 3 is very similar to the oxidative decarboxylation of pyruvate. It is catalysed by 2-oxoglutarate dehydrogenase which is a multienzyme complex and requires the same cofactors as does the pyruvate dehydrogenase complex (page 232). The products of the reaction are succinyl-CoA, which is analogous to acetyl-CoA, and NADH. 

Whereas we have no intention to describe in this review the various aspects of halobacterial metabolism, we would like to mention several unique features of their metabolic system. The conversions of the two 2-oxoacids (pyruvate and oxoglutarate) to their corresponding acyl-CoA thioesters are crucial steps in the two pathways described above. In most eukaryotes and aerobic eubacteria these reactions are catalyzed by the 2-oxoacid dehydrogenase multienzyme complexes that use NAD+ as the final electron acceptor. These complexes are... 

Oxoglutarate undergoes oxidative decarboxylation to succinyl-CoA, via multi-enzyme reaction similar to the reaction pattern of pyruvate. The multi-enzyme complex (mw about 2 x 10 ) is an octamer of an elementary unit containing each of the three contributing enzyme proteins oxoglutarate decarboxylase, dihydro-lipoyl transacetylase, and dihydrolipoyl dehydrogenase. The overall reaction involves thiamine pyrophosphate, lipoic acid, CoASH and NAD succinyl-CoA is the end product ... 

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