Cardiac Phosphatidylethanolamine N-Methylation in Normal and Diabetic Rats Treated with L-Propionylcarnitine

Abstract

The mitochondrial oxidation of long-chain fatty acids is a major pathway for energy production in the heart. L-carnitine, a naturally occurring highly polar compound, is essential for transporting long-chain fatty acids across the inner mitochondrial membrane to the site of oxidation, as well as for the export of intramitochondrially produced short-chain acyl esters and for the disposal of unphysiological acyl metabolites (1,2). In fact, myocardial carnitine deficiency has been documented in several heart diseases, both in humans (3,4) and in experimental animal models (5,6). Accordingly, carnitine deficiency can be seen to be associated with an energy deficit arising from the unavailability of fatty acids within the mitochondria. Moreover, the accumulation of long-chain fatty acids and their derivatives, fatty acyl CoAthio esters and fatty acylcarnitine esters due to carnitine deficiency could produce deleterious effects on cardiac structure and function. These metabolites are active detergents and bind to the cell membranes (7), and there is evidence (7,8) that these lipid intermediates alter the functional properties of the myocardial membranes. It has also been suggested that the long-chain acyl derivatives may contribute to the decline of myocardial contractility and may cause intracellular Ca²⁺ overload (8).