Lu Weizhuo, Wen Jiyue
Department of Pharmacology, School of Pharmaceutical Sciences, Anhui Medical University, Hefei, China.
Medical Branch, Hefei Technology College, Hefei, China.
Mol Neurobiol. 2025 May 6. doi: 10.1007/s12035-025-04968-5.
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 (HS) 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 HS 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 HS content. An accumulating study has revealed that HHcy is a risk factor for ischemic stroke, while HS, 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 HS production and described the roles and relationship among Hcy metabolism and HS in ischemic stroke.
同型半胱氨酸（Hcy）是一种含硫氨基酸，是甲硫氨酸代谢的重要中间产物。Hcy 既可以代谢为半胱氨酸，后者是谷胱甘肽合成和硫化氢（HS）生成的前体，也可以再生成甲硫氨酸。此外，Hcy 代谢对于提供甲基至关重要，而甲基对于 DNA 甲基化必不可少。在 Hcy 代谢的转硫途径中，Hcy 通过含胱硫醚-β-合酶（CBS）和胱硫醚-γ-裂解酶（CSE）的催化酶代谢形成半胱氨酸和 HS。Hcy 代谢相关的酶和辅酶，如维生素 B6、维生素 B12 和叶酸，与高同型半胱氨酸血症（HHcy）密切相关，HHcy 常伴有 HS 含量降低。越来越多的研究表明，HHcy 是缺血性中风的危险因素，而 HS 在生理水平上作为一种气体介质，对缺血性中风具有保护作用。本综述概述了近期与 Hcy 代谢和 HS 生成相关的研究文献数据，并描述了 Hcy 代谢与 HS 在缺血性中风中的作用及关系。
