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Crit Rev Clin Lab Sci. 1999 Aug;36(4):365-406.


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  • 1Department of Laboratory Medicine and Pathobiology, University of Toronto, ON.


Homocysteine is a sulfur-containing amino acid generated through the demethylation of methionine. It is largely catabolized by trans-sulfuration to cysteine, but it may also be remethylated to methionine. Regulation of homocysteine is dependent on nutrient intake, especially folate, vitamins B6 and B12. It is also controlled by individual genetic differences in how vitamins are utilized as cofactors in the reactions controlling homocysteine metabolism. 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. These effects are probably related to its role as a teratogen in the pathogenesis of neural tube defects--genetic variants causing hyperhomocysteinemia are associated with both neural tube defects in susceptible pregnancies and with risks for vaso-occlusive disease in later years. Considerable care must be taken in assaying tHcy. Plasma should be separated shortly after collection to avoid artifactual increases due to synthesis by blood cells in vitro. tHcy concentrations must be interpreted in light of the fact that serum 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 variety 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 treatment of hyperhomocysteinemia with vitamins should lead to a significant reduction in disease risk. Such a possibility lies behind the growing momentum to recommend increased supplements of folate and B vitamins to at-risk populations and patient groups today.

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