Malonyl CoA inhibition of carnitine palmityltransferase in rat heart mitochondria.
The effects of malonyl CoA on carnitine palmityltransferase I (CPT-I), fatty acid-supported state 3 respiration, and carnitine reversal of palmityl CoA inhibition of state 3 respiration and of the adenine nucleotide translocator, were studied in isolated rat heart mitochondria. Malonyl CoA was a potent competitive inhibitor of CPT-I with an I50 of 0.8 microM. Fasting did not affect CPT-I activity or the I50 value of malonyl CoA. Malonyl CoA inhibited fatty acid-supported respiration and prevented carnitine from reversing the inhibition of the adenine nucleotide translocator by palmityl CoA. These findings suggest that malonyl CoA may affect fatty acid oxidation in the heart.
D000214:Acyl Coenzyme A / Q000494:pharmacology*; D000217:Acyltransferases / Q000037:antagonists & inhibitors*; D000818:Animals; D002331:Carnitine / Q000494:pharmacology; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors*; D005215:Fasting; D008293:Malates / Q000378:metabolism; D008316:Malonyl Coenzyme A / Q000494:pharmacology*; D008929:Mitochondria, Heart / Q000201:enzymology; D000226:Mitochondrial ADP, ATP Translocases / Q000037:antagonists & inhibitors; D010101:Oxygen Consumption / Q000187:drug effects; D010171:Palmitoyl Coenzyme A / Q000494:pharmacology; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D051381:Rats
D000214:Acyl Coenzyme A; D008293:Malates; D011773:Pyruvates; D010171:Palmitoyl Coenzyme A; D008316:Malonyl Coenzyme A; C030298:malic acid; D019289:Pyruvic Acid; D000226:Mitochondrial ADP, ATP Translocases; D000217:Acyltransferases; D002334:Carnitine O-Palmitoyltransferase; D002331:Carnitine