Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2105, USA.
J Neurochem. 2010 Apr;113(1):14-26. doi: 10.1111/j.1471-4159.2010.06580.x. Epub 2010 Jan 12.
Nitric oxide (NO) and carbon monoxide (CO) are well established as messenger molecules throughout the body, gasotransmitters, based on striking alterations in mice lacking the appropriate biosynthetic enzymes. Hydrogen sulfide (H(2)S) is even more chemically reactive, but until recently there was little definitive evidence for its physiologic formation. Cystathionine beta-synthase (EC 4.2.1.22), and cystathionine gamma-lyase (CSE; EC 4.4.1.1), also known as cystathionine, can generate H(2)S from cyst(e)ine. Very recent studies with mice lacking these enzymes have established that CSE is responsible for H(2)S formation in the periphery, while in the brain cystathionine beta-synthase is the biosynthetic enzyme. Endothelial-derived relaxing factor activity is reduced 80% in the mesenteric artery of mice with deletion of CSE, establishing H(2)S as a major physiologic endothelial-derived relaxing factor. H(2)S appears to signal predominantly by S-sulfhydrating cysteines in its target proteins, analogous to S-nitrosylation by NO. Whereas S-nitrosylation typically inhibits enzymes, S-sulfhydration activates them. S-nitrosylation basally affects 1-2% of its target proteins, while 10-25% of H(2)S target proteins are S-sulfhydrated. In summary, H(2)S appears to be a physiologic gasotransmitter of comparable importance to NO and carbon monoxide.
一氧化氮（NO）和一氧化碳（CO）是众所周知的全身信使分子，即气体递质，这基于缺乏适当生物合成酶的小鼠中发生的显著变化。硫化氢（H₂S）的化学反应性甚至更强，但直到最近，其生理形成的明确证据还很少。胱硫醚-β-合酶（EC 4.2.1.22）和胱硫醚-γ-裂合酶（CSE；EC 4.4.1.1），也称为胱硫醚，可从半胱氨酸生成 H₂S。最近对缺乏这些酶的小鼠进行的研究表明，CSE 负责外周 H₂S 的形成，而在大脑中，胱硫醚-β-合酶是生物合成酶。CSE 缺失的小鼠肠系膜动脉中内皮衍生的舒张因子活性降低了 80%，从而确立了 H₂S 是主要的生理性内皮衍生舒张因子。H₂S 似乎主要通过其靶蛋白中的 S-硫醇化半胱氨酸来传递信号，类似于 NO 的 S-亚硝化作用。虽然 S-亚硝化作用通常抑制酶，但 S-硫醇化作用会激活它们。S-亚硝化作用基础上影响其靶蛋白的 1-2%，而 10-25%的 H₂S 靶蛋白被 S-硫醇化。总之，H₂S 似乎是一种与 NO 和一氧化碳具有同等重要性的生理性气体递质。
