The pathogenesis of coronary artery disease. A possible role for methionine metabolism

Abstract

Homocystinuria, an abnormality of methionine metabolism, is associated with severe vascular disease in infancy and childhood. Homocysteine is formed during the metabolism of methionine and accumulations of this and of cysteine homocysteine mixed disulfide in the plasma indicate a partial block in the methionine degradation pathway. Methionine metabolism was investigated in 25 patients aged under 50 with angiographically proved coronary artery disease and in 22 control patients, of whom 17 had normal coronary arteries at angiography and 5 were healthy volunteers. After an overnight fast, venous blood was drawn before and 4 hr after oral L methionine, 100 mg/kg. Plasma methionine levels at 4 hr were not different in the 2 groups, but there were significant differences in the levels of cysteine homocysteine mixed disulfide. This was detected in 5 of 22 in the noncoronary group and in higher concentration in 17 of the 25 coronary patients (P<0.01). Age, weight, height, body mass index, glucose tolerance, fasting serum urate, and triglycerides were not different, but serum cholesterol was higher in the coronary patients (P<0.01). These results suggest a reduced ability to metabolise homocysteine in some patients with premature coronary artery disease when this pathway is stressed.