Inhibition of medium and short-chain fatty acid oxidation in rat heart mitochondria by dichloroacetate

The effect of dichloroacetate (DCA) on the oxidation of medium-chain and short-chain fatty acids was studied in rat heart mitochondria. Dichloroacetate (1–10 mM) markedly decreased medium-chain and short-chain fatty acid oxidation (oxygen uptake and release of ¹⁴CO₂ from labelled fatty acids) by heart mitochondria; the oxidation of long-chain fatty acid, however, was unaffected by the compound. The oxidation of acylcarnitines was not influenced by DCA. Dichloroacetate inhibited medium-chain and short-chain fatty acid oxidation by inhibiting the activity of mitochondrial acyl-CoA synthases. Inhibition of the enzyme activity by DCA was rapid and not due to its effect on pyruvate dehydrogenase.