2-Oxoglutarate dehydrogenase system

Early studies showed that the development of neurological abnormalities in thiamin deficiency did not follow the same time course as the impairment of pyruvate and 2-oxoglutarate dehydrogenase or transketolase activities. The brain regions in which metabolic disturbances are most marked were not those that are vulnerable to anatomical lesions. These studies suggested a function for thiamin in the nervous system other than its coenzyme role. 

The second function, and the one pertinent to this section, is the decarboxylation of oxalosuccinic acid to 2-oxoglutaric acid. This is simply a biochemical example of the ready decarboxylation of a P-ketoacid, involving an intramolecular hydrogen-bonded system. This reaction could occur chemically without an enzyme, but it is known that isocitric acid, the product of the dehydrogenation, is still bound to the enzyme isocitrate dehydrogenase when decarboxylation occurs. 

Tissues of the mammalian central nervous system contain a pyridoxal phosphate-dependent glutamate decarboxylase that catalyzes conversion of Glu to y-aminobutyrate (GABA), an inhibitory synaptic transmitter. GABA is degraded by trans-imination with a-oxoglutarate as the acceptor to yield succinic semialdehyde, which then is oxidized to succinate by an NAD-linked dehydrogenase. 

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... 

Thiamine was the first vitamin to have its precise biochemical functions determined. In the form of its pyrophosphate, thiamine participates in several very important enzyme systems namely (1) pyruvate dehydrogenase (page 232) which converts pyruvate to acetyl-CoA and carbon dioxide in the course of carbohydrate breakdown (2) the reaction of the citrate cycle in which oxoglutarate is oxidatively decarboxylated to succinyl-CoA (page 242) (3) the transketolase reaction of the pentose phosphate pathway of glucose breakdown (page 233). 

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