Myocardial carnitine palmitoyltransferase of the mitochondrial outer membrane is not altered by fasting.
The regulation of heart carnitine palmitoyltransferase was studied during the transition to the fasting state. Using decanoyl-CoA or palmitoyl-CoA as substrates, we found no differences in carnitine palmitoyltransferase activity or in its sensitivity to inhibition by malonyl-CoA between fed and fasted states. No cooperativity was seen with either substrate, and the malonyl-CoA-induced shift to sigmoid kinetics normally observed with liver mitochondria was not obvious with heart mitochondria. Analysis of malonyl-CoA inhibition data revealed that mitochondria from rat heart exhibited incomplete maximum inhibition of carnitine palmitoyltransferase (partial inhibition). Homogenization of intact liver mitochondria resulted in a similar pattern of incomplete inhibition and suggested that the malonyl-CoA-insensitive carnitine palmitoyltransferase of the inner membrane was also being assayed. Carnitine palmitoyltransferase in mitochondrial outer membranes, isolated from the heart, proved to be extremely sensitive to malonyl-CoA inhibition and had maximum inhibition values of 90-100% with either decanoyl-CoA or palmitoyl-CoA as substrates, but fasting had no effect. Fasting produced no change in the Ki for malonyl-CoA (0.10 +/- 0.04 and 0.14 +/- 0.02 microM for the fed and fasted groups, respectively). Acyl-CoA chain length specificity was C10 greater than C16 greater than C14 greater than C12 greater than C18 = C8 for carnitine palmitoyltransferase in heart mitochondrial outer membranes. It is concluded that the regulation of carnitine palmitoyltransferase of heart mitochondrial outer membranes differs from regulation of the liver enzyme in three characteristics--the heart enzyme (a) has greater sensitivity to malonyl-CoA inhibition, (b) is resistant to the effects of fasting and (c) has somewhat different acyl-CoA substrate specificity.
Mynatt
R L
RL
Department of Pharmacology, College of Medicine, University of Tennessee, Memphis 38163.
Lappi
M D
MD
Cook
G A
GA
D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism*; D004435:Eating / Q000502:physiology; D005215:Fasting / Q000378:metabolism*; D007425:Intracellular Membranes / Q000201:enzymology*; D007700:Kinetics; D008297:Male; D008929:Mitochondria, Heart / Q000201:enzymology*; D008930:Mitochondria, Liver / Q000201:enzymology; D010171:Palmitoyl Coenzyme A / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013367:Submitochondrial Particles / Q000201:enzymology*; D013379:Substrate Specificity
D010171:Palmitoyl Coenzyme A; D002334:Carnitine O-Palmitoyltransferase