Physiological Roles of Hydrogen Sulfide/Polysulfides and Regulation of their Production

Hydrogen sulfide (H₂S), produced enzymatically, acts as a signaling molecule involved in the regulation of neurotransmission, vascular tone, cytoprotection, inflammation, oxygen sensing, and energy metabolism. Hydrogen polysulfides (H₂S_n, n > 2) and other per- and polysulfides, such as cysteine persulfide, are enzymatically produced to regulate target protein activity. The chemical interaction of H₂S with NO also generates H₂S_n. S-sulfuration (S-sulfhydration) has been proposed as a mode of action of H₂S to regulate the activity of target molecules. H₂S_n S-sulfurate cysteine residues, while H₂S S-sulfurates oxidized cysteine residues such as those S-nitrosylated and S-sulfinated. Transient receptor potential ankyrin 1 (TRPA1) channels, which convert stimulations such as pain, pressure, and temperature to the neuronal signal, were identified as a target of H₂S_n. Recently the channels were found to be involved in the regulation of the transcription/translation of sulfur metabolizing enzymes and the intracellular levels of sulfur containing amino acids, cysteine and methionine, and even those of neurotransmitter GABA. The physiological roles of these molecules will be discussed.