Homocysteine

The loss of a single methyl group from dietary methionine facilitates numerous essential methylation reactions and produces homocysteine, a sulphur containing amino acid. Approximately 50% of homocysteine is re-methylated via a vitamin B12 dependent remethylation cycle in which a methyl group from 5-methyltetrahydrofolate, the main circulatory form of folate, is donated to homocysteine to reform methionine. An alternative route of homocysteine catabolism is via the transsulphuration pathway where homocysteine is condensed with serine to form cystathionine in a vitamin B6 dependent reaction. Nutritional deficiencies and/or inborn errors that affect either of these pathways can lead to hyperhomocysteinemia, characterised by raised plasma concentrations of total homocysteine (tHcy). Elevated total plasma homocysteine (tHcy) is considered to be a significant independent risk factor for various diseases including cardiovascular disease, Alzheimer’s disease and cancer. In the majority of individuals, hyperhomocysteinemia can be successfully corrected through the introduction of nutritional supplements (e.g. folic acid- once a satisfactory vitamin B12 status has been confirmed or the inclusion of adequate dietary folic acid.