Carnitine palmitoyltransferase in the heart is controlled by a different mechanism than the hepatic enzyme.
Diminished sensitivity of hepatic carnitine palmitoyltransferase to inhibition by malonyl-CoA in the fasting and diabetic states is a well-recognized aspect of the regulatory mechanism for hepatic fatty acid oxidation. Inhibition of myocardial carnitine palmitoyltransferase by malonyl-CoA may play an important role in regulation of fatty acid oxidation in the heart, but there has been a discrepancy in data relating to changes in malonyl-CoA sensitivity of the myocardial carnitine palmitoyltransferase during fasting. Analysis of malonyl-CoA inhibition of myocardial carnitine palmitoyltransferase in fasting and fed states under a variety of conditions has indicated that under no condition could any difference be found in malonyl-CoA sensitivity that was attributable to fasting. Proteolysis of the outer carnitine palmitoyltransferase led to artifactual changes in sensitivity due to the appearance of partial inhibition. We have concluded that the sensitivity of myocardial carnitine palmitoyltransferase to malonyl-CoA does not change during fasting. Changes in fatty acid oxidation in the heart are probably due to changes in malonyl-CoA concentrations or to other inhibitors.
Cook
G A
GA
Department of Pharmacology, College of Medicine, University of Tennessee, Memphis 38163.
Lappi
M D
MD
D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010450:Endopeptidases / Q000494:pharmacology; D005215:Fasting / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D008297:Male; D008316:Malonyl Coenzyme A / Q000494:pharmacology*; D008929:Mitochondria, Heart / Q000201:enzymology*; D008930:Mitochondria, Liver / Q000201:enzymology*; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley
D008316:Malonyl Coenzyme A; D002334:Carnitine O-Palmitoyltransferase; D010450:Endopeptidases; D005978:Glutathione