Effect of carboxylic acid xenobiotics and their metabolites on the activity of carnitine acyltransferases.
Salicylyl-CoA and benzoyl-CoA were good inhibitors of carnitine acetyltransferase (CAT), competing with acetyl-CoA with Ki values of 7.5 and 22 microM respectively in the forward direction and with CoA in the reverse reaction with similar Ki values. They were also competitive inhibitors of carnitine octanoyltransferase (Ki = 261 and 295 microM respectively), but were only weakly inhibitory to carnitine palmitoyltransferase. Inhibition of energy production by salicylate may result from the inhibition of CAT by salicylyl-CoA.
Vessey
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DA
Liver Study Unit, Veterans Affairs Medical Center, San Francisco, CA 94121.
Chen
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WW
Ramsay
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RR
D000214:Acyl Coenzyme A / Q000494:pharmacology; D001667:Binding, Competitive; D002264:Carboxylic Acids / Q000378:metabolism / Q000494:pharmacology*; D002333:Carnitine Acyltransferases / Q000037:antagonists & inhibitors / Q000187:drug effects*; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors / Q000187:drug effects*; D005998:Glycine / Q000494:pharmacology; D007700:Kinetics; D015262:Xenobiotics / Q000378:metabolism / Q000494:pharmacology*
D000214:Acyl Coenzyme A; D002264:Carboxylic Acids; D015262:Xenobiotics; C037817:benzoyl-coenzyme A; D002333:Carnitine Acyltransferases; C030162:carnitine octanoyltransferase; D002334:Carnitine O-Palmitoyltransferase; D005998:Glycine