Hydrogen sulfide as a gasotransmitter

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 (H₂S) is even more chemically reactive, but until recently there was little definitive evidence for its physiologic formation. Cystathionine β-synthase (EC 4.2.1.22), and cystathionine γ-lyase (CSE; EC 4.4.1.1), also known as cystathionine, can generate H₂S from cyst(e)ine. Very recent studies with mice lacking these enzymes have established that CSE is responsible for H₂S formation in the periphery, while in the brain cystathionine β-synthase is the biosynthetic enzyme. Endothelial-derived relaxing factor activity is reduced 80% in the mesenteric artery of mice with deletion of CSE, establishing H₂S as a major physiologic endothelial-derived relaxing factor. H₂S 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 H₂S target proteins are S-sulfhydrated. In summary, H₂S appears to be a physiologic gasotransmitter of comparable importance to NO and carbon monoxide.