2-oxoglutarate dehydrogenase Krebs cycle

The situation is simpler for odd numbered fatty acyl derivatives as [3-oxidation proceeds normally until a 5-carbon unit remains, rather than the usual 4-carbon unit. The C5 moiety is cleaved to yield acetyl-CoA (C2) and propionyl-CoA (C3). Propionyl CoA can be converted to succinyl CoA and enter the TCA cycle so the entire molecule is utilized but with a slight reduction in ATP yield as the opportunity to generate two molecules of NADH by isocitrate dehydrogenase and 2-oxoglutarate dehydrogenase is lost because succinyl-CoA occurs after these steps in the Krebs cycle (Figure 7.18). 

Figure 9.2 Summary of reactions of the Krebs cycle. The names of the enzymes are dtrate synthase, aconitase, isodtrate dehydrogenase (there are two enzymes, one ubTizes NAD as the cofactor, the other NADPT it is assumed that the NAD -specific enzyme is that involved in the cycle), oxoglutarate dehydrogenase, sucdnyl CoA synthetase, succinate dehydrogenase, fumarate hydratase, malate dehydrogenase.

The oxygen uptake of a maximally working individual muscle in adult humans has been measured in vivo, enabling the calculation of the flux through the Krebs cycle in that muscle to be made (Appendix 9.10). It is compared with the capacity that is calculated from the maximal in vitro activity of oxoglutarate dehydrogenase, in an extract... 

Table 9.6 Flux through Krebs cycle as calculated from the maximum catalytic activity of oxoglutarate dehydrogenase, measured in extracts of muscle, and from oxygen consumption by muscles working maximally...

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... 

In addition, both 2-oxoglutarate dehydrogenase and isocitrate dehydrogenase are stimulated by a rise in mitochondrial Ca + concentration this is important in stimulating the rate of the Krebs cycle dining exercise. 

In the reductive pathway, the Krebs cycle enzymes are assumed to operate as far as a-oxoglutarate, thus forming a linear pathway. A second linear pathway, from oxaloacetate to malate to fumarate to succinate, is suggested to account for the formation of succinic acid [46]. In support of this new pathway are the observations that (/) yeast contains cytoplasmic malate dehydrogenases capable of converting oxaloacetate to malate, (//) several fumarate reductases (FAD-dependent) have been found in the yeast cytoplasm which have high affinity for fumarate and are unable to oxidize succinate [52] and (Hi) succinate is a significant product of fermentation, i.e. an end product . 

In yeast grown under hypoxic conditions succinate accumulates and the Krebs cycle is split in two branches, one diverging from oxaloacetate to succinate with simultaneous NAD recovery and the other one from oxaloacetate to glutamate, in which the NADP-linked isocitrate dehydrogenase produces the substrates needed for the NADP-linked glutamate dehydrogenase, namely 2-oxoglutarate and NADPH.< )... 

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