Plasma Homocysteine and Cardiovascular Disease

Abstract

Homocysteine is a sulfur amino acid with a free sulfhydryl group (Fig. 1). It was first discovered by du Vigneaud in 1932 as a product of demethylation of methionine (1). The interest in homocysteine was greatly enhanced by the discovery of the inborn errors, homocystinuria. Homocystinuria means the excretion of large amounts of homocystine, the disulfide of homocysteine, in urine secondary to a high level of homocysteine in blood. This disease was first reported in 1962 by Carson and Neill (2), who identified two siblings, aged 4 and 6 years, among 2081 mentally retarded individuals. Almost simultaneously, Gerritsen et al. (3,4) identified urinary homocystine and documented the absence of cerebral cystathionine in a mentally retarded infant with congenital anomalies and thromboembolism. Mudd and co-workers (5) demonstrated lack of cystathionine fj-synthase activity in liver from a typical patient in 1964. Within a few years after the first cases of cystathionine fj-synthase deficiency were discovered, additional patients and their susceptibility to life-threatening vascular disease were described (6-8). In 1969, McCully (9) described vascular lesions, similar to those observed in cystathionine fj-synthase deficiency, in a 7 112-week-old infant dying of homocystinuria caused by a newly discovered defect in cobalamin metabolism. Similar vascular alterations were reported by Kanwar et al. in 1976 (10) in a 10-year-old girl dying of homocystinuria caused by as,10-methylenetetrahydrofo)ate reductase deficiency.