2-Oxoglutaric acid deficiency

Finnic, M.D.A., Cottrall, K., Seakins, J.W.T. and Snedden, W. (1976), Massive excretion of 2-oxoglutaric acid and 3-hydroxyisovaleric acid in a patient with a deficiency of 3-methylcrotonyl Co A carboxylase. Clin. Chim. Acta, 73,513. 

Both hydroxylation reactions in the synthesis of carnitine from trimethyllysine are ascorbic acid-dependent, 2-oxoglutarate-linked, reactions (Section 13.3.3), and impaired synthesis of carnitine probably accounts for the muscle fatigue associated with vitamin C deficiency. 

In thiamine deficiency, therefore, the formation from pyruvate of acetyl-coenzyme A, which is normally followed by the oxidation of the 2-C acetyl fragment to CO2 and H2O via the citric acid cycle is blocked, and the pyruvate formed by glycolysis consequently accumulates. In addition in its role in the oxidative decarboxylation of pyruvate, thiamine pyrophosphate is also needed as a co-enzyme in the similar decarboxylation of the closely related a-oxoglutarate, one of the intermediaries in the citric acid cycle. 

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