Role and Relationship Between Homocysteine and H2S in Ischemic Stroke.

Homocysteine (Hcy), a sulfur-containing amino acid, is an important intermediate product of methionine metabolism. Hcy can be either metabolized to cysteine, a precursor for glutathione synthesis and hydrogen sulfide (H₂S) production, or regenerated back to methionine. Besides, the Hcy metabolism is central to supply methyl groups, which are essential for DNA methylation. In the transsulfuration pathway of Hcy metabolism, Hcy is metabolized to form cysteine and H₂S by catalytic enzymes, containing cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE). Hcy metabolism-related enzymes and coenzymes, such as vitamin B6, vitamin B12, and folic acid, are closely related to hyperhomocysteinemia (HHcy), which is frequently accompanied by reduced H₂S content. An accumulating study has revealed that HHcy is a risk factor for ischemic stroke, while H₂S, served as a gaseous mediator at the physiological level, has protective effects against ischemic stroke. This review outlined the literature data from recent research related to Hcy metabolism and H₂S production and described the roles and relationship among Hcy metabolism and H₂S in ischemic stroke.