Carnitine: vitamin for an insect, vital for man.

Abstract

Carnitine (L-3-hydroxy-4-N-trimethylaminobutyric a id), discovered in 1905, is widely distributed in nature. Interest in the physiology and metabolism of carnitine arose when a dietary factor named vitamin BT, which was found essential for the growth of the mealworm Tenebrio molitor, was identified as carnitine (Carter et al., Arch. Biochem. Biophys., 38, 405-416, 1952). Since 1973, clinical interest in it has intensified as deficiencies of carnitine and of carnitine palmitoyltransferase (CPT) have been implicated in metabolic disorders. It is now known that in a number of life-threatening situations an insufficiency of carnitine occurs and its therapeutic provision has proven beneficial in many such situations. Healthy adults on balanced diets are able to synthesize enough carnitine for their needs, but in certain situations carnitine acquires the status of a conditionally essential nutrient. Many functions have been ascribed to carnitine. These include a role as an essential cofactor in the energy-yielding oxidation of fatty acids in mitochondria, in the chain shortening of long-chain fatty acids in peroxisomes, in the oxidation of branched chain amino acids, in providing an immediate reservoir of activated acetyl groups as acetylcarnitine, in the maintenance of the CoA/acyl-CoA ratio, and in the detoxification of those acyl groups that arise intramitochondrially as acyl-CoA esters but, not being readily oxidizable, result in the tieing up of free CoA. The latter happens in various acyl-CoA dehydrogenase and carboxylase deficiency diseases associated with organic acidurias; the extra demand placed on body carnitine in these cases leads to a deficiency of carnitine. In this group fall some of the patients of Reye-like and of sudden-infant-death syndromes. Some of the highest concentrations of carnitine are found in epididymis and in mature spermatozoa, and a role of carnitine in male reproduction is suspected (hence man in the commentary title). Implicated but less well understood are roles in ammonia detoxification, as an anti-arrhythmic agent for heart, as a hypolipidemic agent in patients with type IV hyperlipoproteinemia, and in the form of acetylcarnitine, as a memory and alertness enhancing agent in the Alzheimer's disease (Kendler, Prev. Med., 15, 373-390, 1986). Evidence so far indicates that the ability of carnitine to facilitate the membrane and (or) transmitochondrial transport of acyl groups as acylcarnitines is central to the various functions of carnitine. Studies of many, including ours, have helped elucidate this process as described below. In the 195bgs, the observations that fatty acylcarnitines appeared as intermediates when fatty acid oxidation by intact mitochondria was stimulated by a component in muscle extracts led to the recognition of the component as