Bełtowski Jerzy
Department of Pathophysiology, Medical University, Lublin, Poland.
Pharmacol Rep. 2015 Jun;67(3):647-58. doi: 10.1016/j.pharep.2015.01.005. Epub 2015 Jan 22.
Hydrogen sulfide (H2S) is the endogenously produced gasotransmitter involved in the regulation of nervous system, cardiovascular functions, inflammatory response, gastrointestinal system and renal function. Together with nitric oxide and carbon monoxide, H2S belongs to a family of gasotransmitters. H2S is synthesized from L-cysteine and/or L-homocysteine by cystathionine β-synthase, cystathionine γ-lyase and cysteine aminotransferase together with 3-mercaptopyruvate sulfurtransferase. Significant progress has been made in recent years in our understanding of H2S biochemistry, signaling mechanisms and physiological role. H2S-mediated signaling may be accounted for not only by the intact compound but also by its oxidized form, polysulfides. The most important signaling mechanisms include reaction with protein thiol groups to form persulfides (protein S-sulfhydration), reaction with nitric oxide and related species such as nitrosothiols to form thionitrous acid (HSNO), nitrosopersulfide (SSNO(-)) and nitroxyl (HNO), as well as reaction with hemoproteins. H2S is enzymatically oxidized in mitochondria to thiosulfate and sulfate by specific enzymes, sulfide:quinone oxidoreductase, persulfide dioxygenase, rhodanese and sulfite oxidase. H2S donors have therapeutic potential for diseases such as arterial and pulmonary hypertension, atherosclerosis, ischemia-reperfusion injury, heart failure, peptic ulcer disease, acute and chronic inflammatory diseases, Parkinson's and Alzheimer's disease and erectile dysfunction. The group of currently available H2S donors includes inorganic sulfide salts, synthetic organic slow-releasing H2S donors, H2S-releasing non-steroidal antiinflammatory drugs, cysteine analogs, nucleoside phosphorothioates and plant-derived polysulfides contained in garlic. H2S is also regulated by many currently used drugs but the mechanism of these effects and their clinical implications are only started to be understood.
硫化氢（H₂S）是内源性产生的气体信号分子，参与调节神经系统、心血管功能、炎症反应、胃肠道系统和肾功能。与一氧化氮和一氧化碳一样，H₂S属于气体信号分子家族。H₂S由胱硫醚β合酶、胱硫醚γ裂解酶、半胱氨酸转氨酶以及3-巯基丙酮酸硫转移酶从L-半胱氨酸和/或L-高半胱氨酸合成。近年来，我们对H₂S生物化学、信号传导机制和生理作用的理解取得了重大进展。H₂S介导的信号传导可能不仅由完整的化合物引起，还由其氧化形式多硫化物引起。最重要的信号传导机制包括与蛋白质硫醇基团反应形成过硫化物（蛋白质S-硫氢化）、与一氧化氮及相关物质如亚硝基硫醇反应形成硫亚硝酸（HSNO）、亚硝基过硫化物（SSNO⁻）和硝酰（HNO），以及与血红素蛋白反应。H₂S在线粒体中被特定酶硫化物：醌氧化还原酶、过硫化物双加氧酶、硫氰酸酶和亚硫酸盐氧化酶酶促氧化为硫代硫酸盐和硫酸盐。H₂S供体对动脉和肺动脉高压、动脉粥样硬化、缺血再灌注损伤、心力衰竭、消化性溃疡病、急慢性炎症性疾病、帕金森病和阿尔茨海默病以及勃起功能障碍等疾病具有治疗潜力。目前可用的H₂S供体包括无机硫化物盐、合成有机缓释H₂S供体、释放H₂S的非甾体抗炎药、半胱氨酸类似物、核苷硫代磷酸酯以及大蒜中含有的植物来源的多硫化物。H₂S也受到许多目前使用的药物的调节，但这些作用的机制及其临床意义才刚刚开始被了解。
