Interacting effects of L-carnitine and malonyl-CoA on rat liver carnitine palmitoyltransferase

Abstract

Malonyl-CoA significantly increased the K(m) for (L)-carnitine of overt carnitine palmitoyltransferase in liver mitochondria from fed rats. This effect was observed when the molar palmitoyl-CoA/albumin concentration ratio was low (0.125-1.0), but not when it was higher (2.0). In the absence of malonyl-CoA, the K(m) for (L)-carnitine increased with increasing palmitoyl-CoA/albumin ratios. Malonyl-CoA did not increase the K(m) for (L)-carnitine in liver mitochondria from 24 h-starved rats or in heart mitochondria from fed animals. The K(m) for (L)-carnitine of the latent form of carnitine palmitoyltransferase was 3-4 times that for the overt form of the enzyme. At low ratios of palmitoyl-CoA/albumin (0.5), the concentration of malonyl-CoA causing a 50% inhibition of overt carnitine palmitoyltransferase activity was decreased by 30% when assays with liver mitochondria from fed rats were performed at 100 μM-instead of 400 μM-carnitine. Such a decrease was not observed with liver mitochondria from starved animals. L-Carnitine displaced [14C]malonyl-CoA from liver mitochondrial bindings sites. D-Carnitine was without effect. (L)-Carnitine did not displace [14C]malonyl-CoA from heart mitochondria. It is concluded that, under appropriate conditions, malonyl-CoA may decrease the effectiveness of (L)-carnitine as a substrate for the enzyme and that (L)-carnitine may decrease the effectiveness of malonyl-CoA to regulate the enzyme.