Homocysteine

Homocysteine is a sulfur-containing amino acid generated through the demeth ylation of methionine. It is largely catabolized by trans-sulfuration to cy steine, but it may also be remethylated to methionine. Regulation of homocy steine is dependent on nutrient intake, especially folate, vitamins B-6 and B-12. It is also controlled by individual genetic differences in how vitam ins are utilized as cofactors in the reactions controlling homocysteine met abolism. In excess quantities, homocysteine is thought to be thrombophilic and to damage the vascular endothelium. Total plasma homocysteine (tHcy) is now established as a clinical risk factor for coronary artery disease, as well as other arterial and venous occlusive disease in adult populations. T hese effects are probably related to its role as a teratogen in the pathoge nesis of neural tube defects - genetic variants causing hyperhomocysteinemi a are associated with both neural tube defects in susceptible pregnancies a nd with risks for vaso-occlusive disease in later years. Considerable care must be taken in assaying tHcy. Plasma should be separated shortly after co llection to avoid artifactual increases due to synthesis by blood cells in vitro. tHcy concentrations must be interpreted in light of the fact that se rum albumin, urate, creatinine, and vitamin concentrations may be important analytical covariates. Moreover, concentrations are age- and sex-dependent and are altered by renal function, hormonal status, drug intake, and a var iety of other common clinical factors. Why then is homocysteine now of such great clinical and scientific interest? If the homocysteine moiety itself is important in the pathogenesis of vaso-occlusive disease, then simple tre atment of hyperhomocysteinemia with vitamins should lead to a significant r eduction in disease risk. Such a possibility lies behind the growing moment um to recommend increased supplements of folate and B vitamins to at-risk p opulations and patient groups today.