THE MEMBRANE-PERTURBING PROPERTIES OF PALMITOYL-COENZYME-A AND PALMITOYLCARNITINE - A COMPARATIVE-STUDY

Fatty acyl-coenzyme A's are temporarily converted into fatty acylcarni tines while transferred across the inner mitochondrial membrane, in th eir catabolic pathway. In search of an explanation for the need of thi s coenzyme exchange, the present work describes comparatively the abil ities of both kinds of fatty acyl derivatives (represented by palmitoy l-coenzyme A and palmitoylcarnitine) in binding to and perturbing the structure of phosphatidylcholine bilayers in the form of large unilame llar vesicles. Both palmitoyl-coenzyme A and palmitoylcarnitine partit ion preferentially into the bilayer lipids, so that their free concent ration in water is in practice negligible. However, palmitoylcarnitine is able to disrupt the membrane barrier to solutes, leading to vesicl e leakage, and, at higher concentrations, it produces complete membran e solubilization, while palmitoyl-coenzyme A produces neither leakage nor solubilization. Palmitoylcarnitine has the properties of many comm only used biochemical detergents. The different behavior of both fatty acyl derivatives helps to explain the need for the transitory coenzym e A/carnitine exchange, and provides a pathogenic mechanism for some g enetic defects of mitochondrial fatty acid transport. Other pathophysi ological processes in which palmitoylcarnitine has been putatively inv olved are examined in light of the above results.