The Effects of Acute and Chronic Up-Regulation of Pyruvate Dehydrogenase on Myocardial Metabolism

Pyruvate dehydrogenase (PDH) is a key regulatory enzyme in cardiac metabolism and is activated by dichloroacetate (DCA). The effects of DCA on PDH and glycolytic flux were investigated in vivo and the perfused heart using hyperpolarized [ ¹³ C]pyruvate and [ ³ H]glucose. PDH flux was enhanced in vivo following acute and chronic DCA treatment. This was accompanied by a decrease in glycolytic flux and lactate production despite the increase in PDH flux. This suggests that either glucose is oxidised more efficiently when coupling between glycolysis and glucose oxidation is enhanced or that increased glucose oxidation leads to inhibition of glycolysis via a negative feedback pathway.

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