Homocysteine

Homocysteine does not occur in the diet but it is an essential intermediate in normal mammalian metabolism of methionine, Each compound, methionine or homocysteine, is the precursor of the other. Similarly, the synthesis of o ne is the mechanism for the detoxification of the other. The ubiquitous met hionine cycle is the metabolic basis for this relationship. In some tissues the transsulfuration pathway diverts homocysteine from the cycle and provi des a means for the synthesis of cysteine and its derivatives. Methionine, (or homocysteine) metabolism is regulated by the disposition of homocystein e between these competing sequences. Both pathways require vitamin-derived cofactors, pyridoxine for transsulfuration and both folate and cobalamin in the methionine cycle. The clinical consequences of disruption of these pat hways was apparent first in rare inborn errors of metabolism that cause hom ocystinuria, but recent studies focus on "hyperhomocysteinemia" - a lesser metabolic impairment that may result from genetic variations, acquired path ology. toxicity and nutritional inadequacy. Hyperhomocysteinemia is an inde pendent risk; factor for thrombovascular diseases however it is not clear w hether the minimally increased concentration of the amino acid is the causa tive agent or merely 3 marker for the pathology. Until we resolve that ques tion we cannot predict the potential efficacy of therapies based on folate administration with or without additional cobalamin and pyridoxine. Publish ed by Elsevier Science Ltd.