Disordered methionine/homocysteine metabolism in premature vascular disease: Its occurrence, cofactor therapy, and enzymology

Abstract

Mild homocysteinemia occurs surprisingly often in patients with premature vascular disease. We studied the possible enzymatic sources of this mild hyperhomocysteinemia and the control of homocysteine levels in plasma by treatment of patients with the cofactors and cosubstrates of homocysteine catabolism. We assessed homocysteine metabolism in 131 patients who had premature disease in their coronary, peripheral, or cerebrovascular circulation by using a standard oral methionine-load test. Impaired homocysteine metabolism occurred in 28 patients. We assayed levels of the primary enzymes of homocysteine catabolism in cultured skin fibroblast extracts from 15 of these 28 patients. The patients' cystathionine β-synthase levels (3.68±2.52 nmol/h per milligram of cell protein, mean±SD) were markedly depressed compared with those from 31 healthy adult control subjects (7.61±4.49, P