Acetyl-L-Carnitine: Metabolism and Applications in Clinical Practice

Recent research has clarified many of the clinical applications of L-Carnitine and its related compounds, leading into new areas of potential use. Promising therapeutic applications of an ester form of carnitine, acetyl-L-Carnitine (ALC) are derived from observations that this compound readily crosses the bloodbrain barrier and improves neuronal energetics and repair mechanisms while modifying acetylcholine production in the CNS. Studies show that HIV infection and CFIDS, Alzheimer’s dementia and depression of the elderly, and diabetic neuropathies may respond positively to ALC administration. Effects of ALC on ethyl alcohol (ETOH) metabolism have been observed and hold significant potential in preventing sequelae of habitual ETOH abuse. (Alt Med Rev 1996;1(2):85-93) Synthesis and Function L-Carnitine is synthesized in mammalian liver, kidney and brain tissue with lysine, methionine and vitamin C among the required substrates and co-factors. The main body stores are in skeletal and cardiac muscle. Acetyl-L-Carnitine is one of the esters of carnitine and is found along with free plasma carnitine and other acyl esters of varying chain length.1 The formation of ALC originates with cytoplasmic thiokinase (See Figure 1) which forms acylcoenzyme A from free-fatty acids, ATP and Coenzyme A (CoA). This substance is combined with carnitine to form acylcarnitine via carnitine palmitoyltransferase I. Entry into the mitochondrial matrix occurs through an exchange system of acylcarnitine/carnitine via carnitine-acylcarnitine translocase. For each acylcarnitine molecule traversing the inner mitochondrial membrane, a molecule of carnitine is shuttled out. On the inner mitochondrial membrane, carnitine palmitoyltransferase II converts acylcarnitine to carnitine, liberating acylCoA. Finally, the production of ALC and CoA from carnitine and acetylCoA (obtained via ß oxidation of acyl CoA) occurs via carnitine acetyltransferase present in the mitochondrial matrix.2 Carnitine and its esters prevent toxic accumulations of fatty acids and acyl CoA (in the cytoplasm and mitochondria, respectively) while providing acetyl CoA for energy generation in the mitochondria. ALC’s enzymatic formation in the mitochondrial matrix is reversible, providing free Coenzyme A and acetyl CoA which can readily be exchanged across membranes, thus providing metabolic energy to intracellular organelles.3 Carnitine acetyltransferase is a reversible enzyme system which appears to be linked with choline acetyltransferase (ChAT), thereby supplying intracellular acetylcholine while the opposite reaction liberates acetylCoA.