HYPERHOMOCYSTEINAEMIA AND VASCULAR-DISEASE

The amino-acid homocysteine plays a crucial role in cell metabolism. I t participates in the remethylation pathway enabling maintenance of ad equate cellular levels of methionine or is catabolized by transsulphur ation, A number of hereditary defects in the enzymes involved in homoc ysteine metabolism and acquired deficiencies in the vitamin cofactors of these enzymes are associated with the development of hyperhomocyste inaemia. The association between high circulating homocysteine levels and premature vascular thrombosis is well established in individuals w ith hereditary homocystinuria, There is now good epidemiological evide nce that mild hyperhomocysteinaemia is an independent risk factor in t he development of arterial disease and venous thrombosis although the causes of the elevated plasma homocysteine are unclear. A good candida te is homozygosity for the common thermolabile variant of methylenetet rahydrofolate reductase but the evidence for a causative association i s conflicting. A number of in vitro effects of homocysteine on vascula r endothelium, platelets and coagulation have been described which may predispose to vascular disease but the exact in vivo mechanisms remai n to be elucidated. Dietary folate supplementation may normalize homoc ysteine in hyperhomocysteinaemic individuals and modify the risk of va scular disease.