[Homocysteine metabolism and risk of cardiovascular diseases: importance of the nutritional status on folic acid, vitamins B6 and B12]

Abstract

Homocysteine is a thiol-containing amino acid derived from methionine metabolism that can be degraded through two enzymatic pathways: remethylation and trans-sulfuration. In remethylation, homocysteine regenerates methionine. In the trans-sulfuration pathway, homocysteine forms cysteine. Due to the rapid metabolic utilization, the plasma concentration of this amino acid is low. Homocysteine circulates as free thiol, homocystine, or bound to free cysteine or to cysteine residues of proteins. Genetic defects of some enzymes in the homocysteine metabolism, or nutritional deficiencies of folic acid, vitamin B6 and B12 lead to an increase in homocysteine plasma concentration and is associated to an increment in cardiovascular diseases. On the basis of clinical and epidemiological studies, homocysteine plasma concentration is considered to be an independent risk factor for the development of atherothrombotic and cardiovascular diseases. The present review describes the homocysteine metabolism, the epidemiological evidence showing the association between homocysteine and the incidence of cardiovascular diseases. The mechanisms by which homocysteine produces vascular damage are indicated. Finally, some recommendations are given for the nutritional therapy of patients with hyperhomocysteinemia.