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.