Carnitine and the Maintenance of Cell Function

Abstract

Carnitine fulfills several important roles in the maintenance of cell function, all of which derive from its ability to form an ester bond, through its β-hydroxy group, with the carboxylate group of fatty acids (or, in a specialised context, branched-chain amino acids). There are two important features associated with the formation of these esters. Firstly, they are formed by the transfer of acyl chains between the respective coenzyme A esters and carnitine, thus resulting in the liberation of unesterified (“free”) coenzyme A which, in turn, can then be esterified to other carboxyl group-containing acyl molecules. In view of the very limited size of the cellular pool of coenzyme A, carnitine and the carnitine acyltransferases that catalyse these reactions play a central role in determining the state of acylation of the cofactor. Secondly, the acylcarnitines so formed are substrates for specific carnitine-acylcarnitine carriers that reside within the cell plasma membrane and certain intracellular membranes. Consequently, whereas acyl-CoA esters are not permeable through membranes, acylcarnitine esters permeate very efficiently those membranes in which the carnitine-acylcarnitine carriers occur. This makes carnitine a very specialised molecule that facilitates the transport of acyl moieties across intracellular membranes while at the same time maintaining the compartmentalization of coenzyme A and acyl-CoA esters that exists in the cell, e.g. between cytosolic and mitochondrial matrix compartments.