The substrate specificity of carnitine acetyltransferase.
1. A study of the acyl group specificity of the carnitine acetyltransferase reaction [acyl-(-)carnitine+CoASH right harpoon over left harpoon (-)-carnitine+acyl-CoA] has been made with the enzyme from pigeon breast muscle. Acyl groups containing up to 10 carbon atoms are transferred and detailed kinetic investigations with a range of acyl-CoA and acylcarnitine substrates are reported. 2. Acyl-CoA derivatives with 12 or more carbon atoms in the acyl group are potent reversible inhibitors of carnitine acetyltransferase, competing with acetyl-CoA. Lauroyl- and myristoyl-CoA show a mixed inhibition with respect to (-)-carnitine, but palmitoyl-CoA competes strictly with this substrate also. Palmitoyl-dl-carnitine shows none of these effects. 3. Ammonium palmitate inhibits the enzyme competitively with respect to (-)-carnitine and non-competitively with respect to acetyl-CoA. 4. It is suggested that a hydrophobic site exists on the carnitine acetyltransferase molecule. The hydrocarbon chain of an acyl-CoA derivative containing eight or more carbon atoms in the acyl group may interact with this, which results in enhanced acyl-CoA binding. Competition occurs between ligands bound to this hydrophobic site and the carnitine binding site. 5. The possible physiological significance of long-chain acyl-CoA inhibition of this enzyme is discussed.
D000217:Acyltransferases / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002331:Carnitine / Q000378:metabolism*; D003065:Coenzyme A / Q000494:pharmacology; D010856:Columbidae; D007700:Kinetics; D009132:Muscles / Q000201:enzymology; D010169:Palmitic Acids / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology
D010169:Palmitic Acids; D000644:Quaternary Ammonium Compounds; D000217:Acyltransferases; D002331:Carnitine; D003065:Coenzyme A