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 the 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.
D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D002210:Caprylates / Q000378:metabolism; D003066:Coenzyme A Ligases / Q000037:antagonists & inhibitors; D003373:Coumaric Acids / Q000494:pharmacology; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D005227:Fatty Acids / Q000378:metabolism*; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains
D000085:Acetates; D002210:Caprylates; D003373:Coumaric Acids; D005227:Fatty Acids; C007175:alpha-cyano-4-hydroxycinnamate; D003999:Dichloroacetic Acid; D003066:Coenzyme A Ligases