Reversible sensitization and desensitization of carnitine palmitoyltransferase I to inhibition by malonyl-CoA in isolated rat liver mitochondria. Significance for the mechanism of malonyl-CoA-induced sensitization.
Preincubation of rat liver mitochondria with 5,5'-dithiobis-(2-nitrobenzoic acid) (Nbs2) followed by removal of excess reagent by washing the mitochondria with 0.5 mM-reduced glutathione resulted in a desensitization of carnitine palmitoyltransferase (CPT) I activity to malonyl-CoA inhibition. The effect was not observed if mitochondria were washed with 0.5 mM-dithiothreitol. The desensitization effect of Nbs2 could be reversed by a second incubation in the presence of 8 microM-malonyl-CoA. In addition, malonyl-CoA, when present simultaneously with Nbs2, protected CPT I activity against the desensitization effect of the thiol-group reagent. These results suggest that malonyl-CoA exerts an effect on one or more thiol groups of the enzyme, and that this effect is related to the ability of the metabolite to sensitize CPT I to malonyl-CoA inhibition.
D000214:Acyl Coenzyme A / Q000494:pharmacology*; D000217:Acyltransferases / Q000037:antagonists & inhibitors*; D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors*; D004228:Dithionitrobenzoic Acid / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008316:Malonyl Coenzyme A / Q000494:pharmacology*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains
D000214:Acyl Coenzyme A; D007527:Isoenzymes; D008316:Malonyl Coenzyme A; D004228:Dithionitrobenzoic Acid; D000217:Acyltransferases; D002334:Carnitine O-Palmitoyltransferase