Effects of carnitine on acetyl-CoA oxidation by heart muscle mitochondria

Abstract

Acetyl-1-C14-CoA was oxidized by heart muscle mitochondria incubated in the absence of ATP and carnitine at a rate approximately 1/100 that at which acetic acid-1-C14 was converted to CO2 in the presence of ATP. Carnitine addition increased the degradation of acetyl-1-C14-CoA by over 50-fold whereas it had no effect on acetate-1-C14 oxidation under conditions described. Carnitine simultaneously augmented oxygen uptake by heart mitochondria in the absence of ATP when acetyl-CoA was the substrate, but had little or no effect on respiration when acetate was the substrate in the presence or absence of ATP. Acetylcarnitine decreased the carnitine enhancement of acetyl-1-C14-CoA conversion to CO2, most likely by isotope dilution via operation of the carnitine acetyltransferase reaction: acetyl-CoA + carnitine ⇆ acetylcarnitine + CoA. It was tentatively concluded that the acetyl group of acetyl-CoA cannot readily penetrate mitochondrial barriers in the absence of a suitable transfer system, but that carnitine acetyltransferase and carnitine may function as a shuttle system to facilitate acetyl-group movement across mitochondrial membranes. Additional data presented demonstrate that carnitine influences the metabolism of the acyl groups of other chain-length acyl-CoA derivatives.