Homocysteine metabolism

Homocysteine is a sulphur-containing amino acid, derived from the metabolism of methionine. Homocysteine concentrations are determined by genetic and nutritional factors; mutations in the genes for enzymes involved in homocysteine metabolism, such as the common 5,10-methylenetetrahydrofolate reductase (MTHFR) 677→T mutation, and deficiencies of vitamins B6, B12 and folic acid are associated with hyperhomocysteinaemia.

Homocysteine and the risk of coronary heart disease

The clinical importance of homocysteine was first recognized in the early 1960s with the recognition of the rare inherited metabolic disorder homocystinuria. Affected children, who have severe hyperhomocysteinaemia (plasma homocysteine >100 μmol/l), develop widespread, premature atherosclerosis affecting large- and medium-sized arteries and, if untreated, die from vascular complications in their teens or 20s. These observations led to the hypothesis that mild–moderate elevations in plasma homocysteine (>15 μmol/l) might contribute to the development of vascular disease in adults. This possibility has now been evaluated in more than 30 cross-sectional and prospective studies, involving over 10000 subjects [1]. The results have been remarkably consistent, with few exceptions. Elevated plasma homocysteine is an independent risk factor for peripheral vascular disease, cerebrovascular disease and coronary heart disease (CHD); in patients with CHD, homocysteine concentrations of 9, 15 and 20 μmol/l predict total mortality ratios of 1.9, 2.8 and 4.5, respectively [2]. Elevated homocysteine is common, and concentrations exceeding the upper limit of normal (15 μmol/l) are found in almost 30% of patients with vascular disease.