Peculiarities of the inhibition of the pyruvate dehydrogenase complex by thiamine thiazolone diphosphate in vitro and in intact mitochondria

Thiamine thiazolone diphosphate (TTPP) possesses the ability to penetrate through the mitochondrial membrane and inhibit the pyruvate dehydrogenase complex in intact mitochondria, TTPP inhibits the activity of the complex of animal origin according to a mixed type (K/sub i/ 5 x 10/sup -8/ M) and yeast pyruvate decarboxylase according to a competitive type (K/sub i/ 5 x 10/sup -6/ M) with respect to thiamine diphosphate (TPP). Decarboxylation of pyruvate in intact and lysed rat liver and brain mitochondria is inhibited in the presence of TTPP significantly more weakly than the total activity of the pyruvate dehydrogenase complex, determined according to the formation of acetyl-CoA. It is suggested that TTPP, as an analog of the transition state, acts only in dehydrogenase reactions but not at the stage of simple decarboxylation of pyruvate.