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 (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.
Gadalla
Moataz M
MM
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2105, USA.
Snyder
Solomon H
SH
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002248:Carbon Monoxide / Q000378:metabolism; D003541:Cystathionine beta-Synthase / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000172:deficiency / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D045462:Endothelium-Dependent Relaxing Factors / Q000494:pharmacology; D006801:Humans; D006862:Hydrogen Sulfide / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy; D051379:Mice; D018345:Mice, Knockout; D008958:Models, Molecular; D009569:Nitric Oxide / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D045462:Endothelium-Dependent Relaxing Factors; D009569:Nitric Oxide; D002248:Carbon Monoxide; D003541:Cystathionine beta-Synthase; D003542:Cystathionine gamma-Lyase; D006862:Hydrogen Sulfide