L-carnitine acyltransferase in intact peroxisomes is inhibited by malonyl-CoA.
Inhibition of the overt mitochondrial carnitine palmitoyltransferase by malonyl-CoA is important in the regulation of fatty acid oxidation. In the past, the contribution of peroxisomal carnitine acyltransferase activity to the generation of medium- and long-chain acylcarnitines in the cytoplasm has been ignored. On the basis of marker enzyme levels, we now estimate that peroxisomal palmitoyltransferase activity constitutes about 20% of the peroxisomal plus overt-mitochondrial pool in fed rat liver. When assayed in situ, both the palmitoyltransferase and decanoyltransferase activities of gradient-purified peroxisomes are sensitive to malonyl-CoA, with up to 90% inhibition reached at less than 10 microM-malonyl-CoA. Very similar results were obtained with intact gradient-purified mitochondria from the same livers. In addition, the acyl-CoA substrate chain-length specificity was identical in both the peroxisomes and the mitochondria, with a decanoyltransferase/palmitoyltransferase ratio of 2. Thus the overt carnitine acyltransferase activities in peroxisomes and mitochondria have the same properties. Further, the malonyl-CoA sensitivity of the peroxisomal activity is lost on solubilization, as has been observed for the overt mitochondrial enzyme. It is suggested that malonyl-CoA inhibition of the peroxisomal enzyme as well as of the mitochondrial enzyme is important for the regulation of mitochondrial fatty acid oxidation.
Derrick
J P
JP
Department of Biochemistry, University of Cambridge, U.K.
Ramsay
R R
RR
D000214:Acyl Coenzyme A / Q000494:pharmacology*; D000217:Acyltransferases / Q000037:antagonists & inhibitors*; D000818:Animals; D002333:Carnitine Acyltransferases / Q000037:antagonists & inhibitors*; D002334:Carnitine O-Palmitoyltransferase / Q000032:analysis; D008099:Liver / Q000201:enzymology; D008297:Male; D008316:Malonyl Coenzyme A / Q000494:pharmacology*; D008830:Microbodies / Q000201:enzymology; D008930:Mitochondria, Liver / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D013379:Substrate Specificity
D000214:Acyl Coenzyme A; D008316:Malonyl Coenzyme A; D000217:Acyltransferases; D002333:Carnitine Acyltransferases; D002334:Carnitine O-Palmitoyltransferase