Abstract
SIGNIFICANCE: Hydrogen sulfide (H(2)S) metabolism leads to the formation of oxidized sulfide species, including polysulfide, persulfide, and others. Evidence is emerging that many biological effects of H(2)S may indeed be due to polysulfide and persulfide activation of signaling pathways and reactivity with discrete small molecules. Recent Advances: Exogenous oxidized sulfide species, including polysulfides, are more reactive than H(2)S with a wide range of molecules. Importantly, endogenous polysulfide and persulfide formation has been reported to occur via transsulfuration enzymes, cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS). CRITICAL ISSUES: In light of the recent understanding of oxidized sulfide metabolite formation and reactivity, comparatively few studies have been reported comparing cellular biological and in vivo effects of H(2)S donors versus polysulfide and persulfide donors. Likewise, it is equally unclear when, how, and to what extent persulfide and polysulfide formation occurs in vivo under pathophysiological conditions. FUTURE DIRECTIONS: Additional studies regarding persulfide and polysulfide formation and molecular reactions are needed in nearly all aspects of biology to better understand how sulfide metabolites contribute to key chemical biology reactions involved in cardiovascular health and immune responses. Antioxid. Redox Signal. 27, 634-653.