The role of acylcarnitine esters and carnitine palmityltransferase in the transport of fatty acyl groups across mitochondrial membranes.

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Abstract
Carnitine-induced stimulation of palmitate oxidation by heart muscle mitochondria was competitively inhibited by (+)-palmitylcarnitine. Conditions were reported in which availability of carnitine determined the rate of fatty acid oxidation. The probable site of inhibition of utilization of palmitate and palmityl CoA by (+)-palmitylcarnitine was at the level of mitochondrial-bound carnitine palmityltransferase. The optically unnatural carnitine derivative did not, however, inhibit solubilized enzyme preparations. Data were consonant with a previously developed hypothesis concerning carnitine action on fatty acid metabolism in which acylcarnitine derivatives were proposed as essential intermediates. Results suggested that carnitine palmityltransferase may be located on mitochondrial membranes separating the site of fatty acid activation from the site of fatty acid oxidation. Evidence was presented which supported the postulate that an interface between sites of fatty acid activation and oxidation serves as a barrier for the passage of the fatty acyl portion of acyl CoA derivatives, but not the fatty acyl group of acylcarnitine derivatives. It was inferred that carnitine palmityltransferase functions both as a fatty acyl transferase and as a fatty acyl translocase between the above two sites or compartments of the mitochondrion. It was concluded that ([long dash])-palmitylcarnitine is an obligatory intermediate in the carnitine-induced enhancement of palmitic acid oxidation by heart mitochondria.