Homocysteine is a product of methionine metabolism. Evidence suggests that high levels of plasma homocysteine are a risk factor for cardiovascular disease. As methionine metabolism proceeds, homocysteine is produced and this homocysteine is then converted to cysteine or back to methionine through various pathways that rely on B vitamins. The B vitamin required for the metabolisms of homocysteine to cysteine is vitamin B6, and the B vitamins required for the metabolism of homocysteine to methionine are vitamin B12 and folic acid. Deficiencies of these vitamins cause a buildup of homocysteine in the cells and this then spills over into the plasma. As plasma levels rise, the homocysteine may interfere with endothelial function through the generation of oxidative stress, In particular, the oxidative stress inhibits the function of nitric oxide synthase and this lower levels of nitric oxide, the latter being required for the correct dilation of blood vessels in response to flow.
As homocysteine builds up in the plasma evidence suggest that it also displaces cysteine residues in normal plasma proteins. For example, in one study, researchers1 analysed the plasma proteins of subjects with homocysteinaemia, a disorder characterised by higher than normal levels of homocysteine in the plasma. In these subjects, nearly all the cysteine residues normally found sulfhydryl-binding sites of plasma protein had been replaced by homocysteine. The majority of the cysteine in the plasma of the proteins was in the form of mixed disulfide with half homocysteine, rather than being free in the plasma or being bound to plasma proteins. The clinical relevance of this binding of homocysteine to plasma protein in place of normal amino acid residues in not known. However, the high homocysteine seen in patients with homocysteinaemia suggests that this is pathological in nature, and may therefore have physiological consequences.
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