2-Oxoglutarate dehydrogenase

Enzymes a) citrate synthase b) aconitase c) isocitrate dehydrogenase d) a-oxoglutarate dehydrogenase e) succiny CoA synthetase f) succinate dehydrogenase g) fumarase h) malate dehydrogenase i) nucleoside diphosphokinase. 

Figure 5.3 Major control points of glycolysis and the TCA cycle. Enzymes I, hexokinase II, phosphofructokinase III, pyruvate kinase IV, pyruvate dehydrogenase V, citrate synthase VI, aconitase VII, isocitrate dehydrogenase VIII, a-oxoglutarate dehydrogenase.

The diagram looks very promising in terms of citric acid formation in that a-oxoglutarate dehydrogenase is inactive, isodtrate dehydrogenase has veiy low activity and aconitase equilibrates 90% towards dtric add. 

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...

Muscle Oxoglutarate dehydrogenase activity Oxygen consumption ... 

As with some other enzymes involved in the generation of ATP in the mitochondria (e.g. oxoglutarate dehydrogenase), aconitase possesses an iron-sulphur complex in its... 

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... 

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). 

The next step, the formation of succinyl CoA, also involves one oxidation and one decarboxylation. it is catalyzed by 2-oxoglutarate dehydrogenase, a multienzyme complex closely resembling the PDH complex (see... 

King RF, Macfie J, Hill G (1981) Activities of hexokinase, phosphofructokinase, fructose bisphosphatase and 2-oxoglutarate dehydrogenase in muscle of normal subjects and very ill surgical patients. Clin Sci 60 451-456... 

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