Myocardial Carnitine Transport

In mammals, carnitine is synthesized from proteic trimethyllysine in the liver, brain and (in human) kidneys. The hydroxylase catalyzing the last step (deoxycarnitine----carnitine) is missing in the remaining tissues, which are thus entirely dependent on carnitine uptake from the blood. On the basis of experimental evidence, or reasonable assumptions, an interorgan transport of carnitine, carnitine precursors and derivatives is described. In particular, evidence demonstrating a bidirectional exchange between carnitine and deoxycarnitine across cardiac sarcolemma have been provided both in vitro and in vivo experiments. It has been demonstrated that in heart slices carnitine-deoxycarnitine exchange, occurring in a close one to one ratio, is (i) insensitive to both glycolysis and oxidative phosphorylation inhibitors and (ii) sensitive to thiol reagents, such as NEM and Mersalyl. It is assumed that deoxycarnitine is released from muscles into the blood, taken up by the liver, or kidneys, to be hydroxylated to carnitine and the latter returned to the muscles. In vivo evidence for carnitine-deoxycarnitine exchange has been obtained by administering carnitine, or deoxycarnitine, to rats and measuring deoxycarnitine and carnitine, respectively, in different tissues and urine. The results clearly indicate that carnitine administration displaces endogenous deoxycarnitine from tissues and vice versa, thus further supporting the existence of a carnitine-deoxycarnitine exchange process.