PYRUVATE AND a-KETOGLUTARATE METABOLISM IN THIAMINE DEFICIENCY*

One obvious explanation for the effect of high fat diets in lowering the requirement for thiamine has been that fat metabolism does not require thiamine, while carbohydrate metabolism does. This explanation finds considerable support in one of the known functions of thiamine pyrophosphate. According to current theory, carbohydrate is oxidized to pyruvate, and pyruvate must be decarboxylated for further oxidation by way of the citric acid cycle. Fatty acids, on the other hand, are oxidized to form a a-carbon compound and can undergo further oxidation in the citric acid cycle without a decarboxylation step. Since thiamine pyrophosphate is necessary for oxidation of pyruvate, probably in the decarboxylation step, thiamine-deficient animals might be able to maintain a more nearly normal metabolism on a diet high in fat. If this explanation is correct, thiamine deficiency should not affect to any great extent other metabolic reactions in which fat is involved. According to present knowledge, however, thiamine pyrophosphate is a coenzyme for a-ketoglutarate metabolism (l-4), and fat requires for its complete metabolism the oxidation of cr-ketoglutarate as an intermediate step. The present experiments compare the effects of thiamine deficiency on a-ketoglutarate oxidation and on pyruvate oxidation. The results are in accord with the concept that the effect of high fat diets on thiamine deficiency is due to the maintenance of a more nearly normal metabolism.