Plasma Homocysteine in Renal Failure, Diabetes Mellitus, and Alcoholism

Homocysteine, a sulfhydryl amino acid, is the demethylated derivative of methionine [1]. Greatly elevated plasma levels of homocysteine are found in subjects with homocystinuria [1]. These patients exhibit early arteriosclerosis as well as arterial and venous thrombosis. Recently, milder hyper-homocysteinemia has been reported in patients with premature vascular disease, many of whom may be heterozygous for homocystinuria [2–8]. Other conditions such as folate and vitamin B12 deficiency also cause elevation of homocysteine in plasma [1,9,10]. Adenosyl-methionine, the precursor of homocysteine, is the principal methyl donor in mammals. After a methyl transfer reaction (transmethylation), adenosyl-homocysteine is hydrolyzed to homocysteine and adenosine. Homocysteine may be either catabolized in the transsulfuration pathway via cystathionine and cysteine to inorganic sulfur, or remethylated back to methionine, mainly by the folate- and vitamin B12-dependent enzyme methionine synthase [1]. Patients with chronic renal failure, whether dialyzed or not, have a high risk of premature vascular disease, especially coronary and cerebrovascular accidents [11,12]. Among other factors that could increase the risk of vascular disease in chronic renal failure is mild hyperhomocysteinemia. Likewise, patients with diabetes mellitus and patients with heavy alcohol consumption have an increased risk of premature vascular disease, which could possibly be related to hyperhomocysteinemia. It is therefore of interest to study plasma homocysteine in all these diseases.