Hepatic and cardiac carnitine palmitoyltransferase activity. Effects of adriamycin and galactosamine.
Carnitine palmitoyltransferase (CPT) activity is located on both the outer and inner sides of the mitochondrial inner membrane and is influenced by the surrounding lipids of the inner mitochondrial membrane. Both adriamycin and galactosamine interact with mitochondrial lipids as a part of their mechanism of toxicity, and thus these agents might be expected to affect CPT activity. Addition of adriamycin to both intact rat liver and heart mitochondria (CPT-A, outer CPT) and inverted submitochondrial vesicles (CPT-B, inner CPT) depressed CPT in the forward direction of reaction (palmitoyl-l-carnitine formation), but the CPT-B activity was more sensitive to the inhibitor. Adriamycin depressed the CPT-A reverse reaction (palmitoyl-CoA formation) to 40% of control, but it had no effect on the CPT-B reverse reaction. In vivo galactosamine administration depressed CPT-A and CPT-B 20-30% and did not affect subsequent action of in vitro adriamycin. Addition of cardiolipin (0.25 to 1.0 mg/assay) increased activity of the CPT-A forward reaction of both control and galactosamine-treated rats, but it did not affect CPT-B activity. The results suggest that CPT-A and CPT-B may be influenced differently by perturbants that affect lipids of the membrane.
Brady
L J
LJ
Department of Food Science and Human Nutrition, Washington State University, Pullman 99164-2032.
Brady
P S
PS
D000217:Acyltransferases / Q000032:analysis*; D000818:Animals; D002308:Cardiolipins / Q000494:pharmacology; D002334:Carnitine O-Palmitoyltransferase / Q000032:analysis*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology*; D005688:Galactosamine / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000201:enzymology*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains
D002308:Cardiolipins; D005688:Galactosamine; D004317:Doxorubicin; D000217:Acyltransferases; D002334:Carnitine O-Palmitoyltransferase