Enzymology of H 2 S Biogenesis, Decay and Signaling

SIGNIFICANCE: Hydrogen sulfide (H2S), produced by the desulfuration of cysteine or homocysteine, functions as a signaling molecule in an array of physiological processes including regulation of vascular tone, the cellular stress response, apoptosis, and inflammation. RECENT ADVANCES: The low steady-state levels of H2S in mammalian cells have been recently shown to reflect a balance between its synthesis and its clearance. The subversion of enzymes in the cytoplasmic trans-sulfuration pathway for producing H2S from cysteine and/or homocysteine versus producing cysteine from homocysteine, presents an interesting regulatory problem. CRITICAL ISSUES: It is not known under what conditions the enzymes operate in the canonical trans-sulfuration pathway and how their specificity is switched to catalyze the alternative H2S-producing reactions. Similarly, it is not known if and whether the mitochondrial enzymes, which oxidize sulfide and persulfide (or sulfane sulfur), are regulated to increase or decrease H2S or sulfane-sulfur pools. FUTURE DIRECTIONS: In this review, we focus on the enzymology of H2S homeostasis and discuss H2S-based signaling via persulfidation and thionitrous acid.