title: Homocysteine.
abstract: 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 one is the mechanism for the detoxification of the other. The ubiquitous methionine cycle is the metabolic basis for this relationship. In some tissues the transsulfuration pathway diverts homocysteine from the cycle and provides a means for the synthesis of cysteine and its derivatives. Methionine, (or homocysteine) metabolism is regulated by the disposition of homocysteine 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 pathways was apparent first in rare inborn errors of metabolism that cause homocystinuria, but recent studies focus on "hyperhomocysteinemia"--a lesser metabolic impairment that may result from genetic variations, acquired pathology, toxicity and nutritional inadequacy. Hyperhomocysteinemia is an independent risk factor for thrombovascular diseases however it is not clear whether the minimally increased concentration of the amino acid is the causative agent or merely a marker for the pathology. Until we resolve that question we cannot predict the potential efficacy of therapies based on folate administration with or without additional cobalamin and pyridoxine.
authors.affiliation: VA Medical Center, Washington DC 20422, USA. James.finkelstein@med.va.gov
authors.forename: J D
authors.initials: JD
authors.lastname: Finkelstein
authors.forename: J J
authors.initials: JJ
authors.lastname: Martin
mesh_terms: D000818:Animals; D006710:Homocysteine / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D006801:Humans
chemical_list: D006710:Homocysteine