Metabolism of homocysteine and risk of cardiovascular diseases: Importanceof folic acid, vitamins B-6 and B-12 nutritional status

Homocysteine is a thiol-containing amino acid derived from methionine metab olism that can be degraded through two enzymatic pathways: remethylation an d 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 enzym es in the homocysteine metabolism, or nutritional deficiencies of folic aci d, vitamin B-6 and B-12 lead to all increase in homocysteine plasma concent ration and is associated to an. increment in cardiovascular diseases. On th e basis of clinical and epidemiological studies, homocysteine plasma concen tration is considered to be an independent risk factor for the development of atherothrombotic and cardiovascular diseases. The present review describ es the homocysteine metabolism, the epidemiological evidence showing the as sociation between homocysteine and the incidence of cardiovascular diseases . The mechanisms by which homocysteine produces vascular damage are indicat ed. Finally, some recommendations are given for the nutritional therapy of patients with hyperhomocysteinemia.