Homocysteine and homocysteine-related compounds: An overview of the roles in the pathology of the cardiovascular and nervous systems

Homocysteine, an amino acid containing a sulfhydryl group, is an intermediate product during metabolism of the amino acids methionine and cysteine. Hyperhomocysteinemia is used as a predictive risk factor for cardiovascular disorders, the stroke progression, screening for inborn errors of methionine metabolism, and as a supplementary test for vitamin B12 deficiency. Two organic systems in which homocysteine has the most harmful effects are the cardiovascular and nervous system. The adverse effects of homocysteine are achieved by the action of several different mechanisms, such as overactivation of N-methyl-D-aspartate receptors, activation of Toll-like receptor 4, disturbance in Ca2+ handling, increased activity of nicotinamide adenine dinucleotide phosphate-oxidase and subsequent increase of production of reactive oxygen species, increased activity of nitric oxide synthase and nitric oxide synthase uncoupling and consequent impairment in nitric oxide and reactive oxygen species synthe