Inhibition of carnitine acetyltransferase by metabolites of 4-pentenoic acid.
The inhibition of carnitine acetyltransferase (EC 2.3.1.7) by metabolites of 4-pentenoic acid was studied. 3-Keto-4-pentenoyl-CoA, a beta-oxidation metabolite of 4-pentenoic acid, was found to be an effective inhibitor of the enzyme in the presence, but not in the absence of L-carnitine. Since acetyl-CoA protects the enzyme against this inhibition, 3-keto-4-pentenoyl-CoA seems to be an active site-directed inhibitor. 3-Keto-4-pentenoyl-CoA, which is a substrate of carnitine acetyltransferase, causes the irreversible inactivation of the enzyme. All observations together lead to the suggestion that 3-keto-4-pentenoyl-CoA is a mechanism-based inhibitor of carnitine acetyltransferase.
D000123:Acetyltransferases / Q000037:antagonists & inhibitors*; D000214:Acyl Coenzyme A / Q000378:metabolism; D000818:Animals; D002332:Carnitine O-Acetyltransferase / Q000037:antagonists & inhibitors*; D010856:Columbidae; D005229:Fatty Acids, Monounsaturated; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D007700:Kinetics; D008956:Models, Chemical; D009132:Muscles / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013552:Swine
D000214:Acyl Coenzyme A; D005229:Fatty Acids, Monounsaturated; D005231:Fatty Acids, Unsaturated; D013438:Sulfhydryl Compounds; C046107:3-keto-4-pentenoyl-coenzyme A; C009785:4-pentenoic acid; D000123:Acetyltransferases; D002332:Carnitine O-Acetyltransferase