Hormonal Regulation of Homocysteine

Abstract

Molecular Medicine Research Group, Biomedical Research Institute, University of Warwick, Coventry, United Kingdom. HOMOCYSTEINE (Hcy), formed by demethylation of methionine, is a sulphur-containing non-essential amino acid. Elevated plasma levels of Hcy, denoted hyperhomocysteinaemia, has been recognised as an independent risk factor for cardiovascular disease (CVD) including the increased risk of atherosclerotic coronary, cerebral and peripheral vascular disease, and also deep vein thrombosis and thromboembolic disease.1–3 A clear association between plasma Hcy concentrations and mortality has been demonstrated in patients with angiographic coronary artery disease,4 and a 5-μM ”rise” in plasma Hcy concentrations has been shown to increase risk of CVD by some 80% in women and 60% in men.5 The adverse effects of Hcy on the cardiovascular system include endothelial dysfunction, oxidation of low-density lipoprotein, increased platelet adhesiveness, and activation of the coagulation system6; lowering plasma Hcy slows the progression of subclinical atherosclerosis7 and also improves endothelial function.8 Although Hcy is considered an independent cardiovascular risk factor by many investigators, others have not reported such an association.9,10 A number of factors determine plasma Hcy concentrations, including inherited disorders affecting enzymatic activities in Hcy metabolism, nutritional deficiencies,6 including vitamin B12, folate, and vitamin B6, which again can result in blockade of the Hcy metabolic pathway. Elevated plasma Hcy has been associated with increasing age, haematocrit, uric acid, creatinine concentrations, systolic blood pressure, and elevated cholesterol.11,12 However, collectively these factors do not entirely account for elevated plasma Hcy levels, especially in patients with vascular disease. It is therefore clear that other nongenetic factors alter plasma Hcy concentrations. In this article, the effects that hormones have on Hcy concentrations and metabolism are discussed.