Abstract:Background:Hydrogen sulfide (H 2 S) modulates physiological processes in mammals. Results: The reactivity of H 2 S toward disulfides (RSSR) and albumin sulfenic acid (RSOH) to form persulfides (RSSH) was assessed. Conclusion: H 2 S is less reactive than thiols. Persulfides have enhanced nucleophilicity. Significance: This kinetic study helps rationalize the contribution of the reactions with oxidized thiol derivatives to H 2 S biology.
“…In the case of higher order polysulfides, the same trend is expected. Importantly, the pK a of an RSSH species is typically 1–2 pK a units lower than the corresponding RSH species 42 (and possibly much lower 32), indicating that reactions with an RSS − leaving group should predominate over a reaction with an RS − leaving group. Thus, an RSS n R ( n > 1) species should be more electrophilic than the corresponding disulfide.…”
Section: The Chemical Biology Of Hydropersulfides and Polysulfidesmentioning
confidence: 99%
“…These reactions have been studied extensively 21, 22, 31, 32 and they represent possible routes of endogenous hydropersulfide formation. It needs to be mentioned, however, that formation of hydropersulfides via Reaction 1 has been questioned on the basis of the low reducing power of H 2 S, its relatively low concentration and the high concentrations of GSH 33.…”
Section: The Generation and Prevalence Of Hydropersulfides And Polysumentioning
The chemical biology of thiols (RSH, e.g., cysteine and cysteine‐containing proteins/peptides) has been a topic of extreme interest for many decades due to their reported roles in protein structure/folding, redox signaling, metal ligation, cellular protection, and enzymology. While many of the studies on thiol/sulfur biochemistry have focused on thiols, relatively ignored have been hydropersulfides (RSSH) and higher order polysulfur species (RSSnH, RSSnR, n > 1). Recent and provocative work has alluded to the prevalence and likely physiological importance of RSSH and related RSSnH. RSSH of cysteine (Cys‐SSH) has been found to be prevalent in mammalian systems along with Cys‐SSH‐containing proteins. The RSSH functionality has not been examined to the extent of other biologically relevant sulfur derivatives (e.g., sulfenic acids, disulfides, etc.), whose roles in cell signaling are strongly indicated. The recent finding of Cys‐SSH biosynthesis and translational incorporation into proteins is an unequivocal indication of its fundamental importance and necessitates a more profound look into the physiology of RSSH. In this Review, we discuss the currently reported chemical biology of RSSH (and related species) as a prelude to discussing their possible physiological roles.
“…In the case of higher order polysulfides, the same trend is expected. Importantly, the pK a of an RSSH species is typically 1–2 pK a units lower than the corresponding RSH species 42 (and possibly much lower 32), indicating that reactions with an RSS − leaving group should predominate over a reaction with an RS − leaving group. Thus, an RSS n R ( n > 1) species should be more electrophilic than the corresponding disulfide.…”
Section: The Chemical Biology Of Hydropersulfides and Polysulfidesmentioning
confidence: 99%
“…These reactions have been studied extensively 21, 22, 31, 32 and they represent possible routes of endogenous hydropersulfide formation. It needs to be mentioned, however, that formation of hydropersulfides via Reaction 1 has been questioned on the basis of the low reducing power of H 2 S, its relatively low concentration and the high concentrations of GSH 33.…”
Section: The Generation and Prevalence Of Hydropersulfides And Polysumentioning
The chemical biology of thiols (RSH, e.g., cysteine and cysteine‐containing proteins/peptides) has been a topic of extreme interest for many decades due to their reported roles in protein structure/folding, redox signaling, metal ligation, cellular protection, and enzymology. While many of the studies on thiol/sulfur biochemistry have focused on thiols, relatively ignored have been hydropersulfides (RSSH) and higher order polysulfur species (RSSnH, RSSnR, n > 1). Recent and provocative work has alluded to the prevalence and likely physiological importance of RSSH and related RSSnH. RSSH of cysteine (Cys‐SSH) has been found to be prevalent in mammalian systems along with Cys‐SSH‐containing proteins. The RSSH functionality has not been examined to the extent of other biologically relevant sulfur derivatives (e.g., sulfenic acids, disulfides, etc.), whose roles in cell signaling are strongly indicated. The recent finding of Cys‐SSH biosynthesis and translational incorporation into proteins is an unequivocal indication of its fundamental importance and necessitates a more profound look into the physiology of RSSH. In this Review, we discuss the currently reported chemical biology of RSSH (and related species) as a prelude to discussing their possible physiological roles.
“…Additionally, we showed that CysSSH is biosynthesised from cystine by cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE), which in turn may contribute to the production of GSSH and other CysSSH derivatives formed in humans 14 15 18. The antioxidant capacity and reactivity of GSSH and CysSSH are approximately 10–100 times greater than those of GSH and cysteine (CysSH) 14 15 17 19. Currently, the amounts of reactive persulfide and polysulfide species and their biosynthesis in the lungs of patients with COPD remain unknown.…”
We have identified a decrease in reactive persulfide and polysulfide species in the lungs of patients with COPD. These data suggest that the newly detected antioxidants reactive persulfides and polysulfides could be associated with the redox balance in the lungs of patients with COPD.
“…Despite an appreciation of sulfide signaling, the mechanisms of how H 2 S functions as a signaling molecule remain under investigation (12). Emerging evidence suggests that highly oxidized sulfur species, termed reactive sulfur species (RSS), are the actual sulfide-signaling species (13)(14)(15)(16). These include HS•, cysteine sulfenic acids, cysteine persulfides, glutathione persulfides (GSSHs), and inorganic polysulfide species, which catalyze persulfidation of specific proteins and enzymes (13,(17)(18)(19)(20), although the functional impact of this protein modification is as yet not generally clear (17).…”
Sulfide was used as an electron donor early in the evolution of photosynthesis, with many extant photosynthetic bacteria still capable of using sulfur compounds such as hydrogen sulfide (H 2 S) as a photosynthetic electron donor. Although enzymes involved in H 2 S oxidation have been characterized, mechanisms of regulation of sulfide-dependent photosynthesis have not been elucidated. In this study, we have identified a sulfide-responsive transcriptional repressor, SqrR, that functions as a master regulator of sulfide-dependent gene expression in the purple photosynthetic bacterium Rhodobacter capsulatus. SqrR has three cysteine residues, two of which, C41 and C107, are conserved in SqrR homologs from other bacteria. Analysis with liquid chromatography coupled with an electrospray-interface tandem-mass spectrometer reveals that SqrR forms an intramolecular tetrasulfide bond between C41 and C107 when incubated with the sulfur donor glutathione persulfide. SqrR is oxidized in sulfidestressed cells, and tetrasulfide-cross-linked SqrR binds more weakly to a target promoter relative to unmodified SqrR. C41S and C107S R. capsulatus SqrRs lack the ability to respond to sulfide, and constitutively repress target gene expression in cells. These results establish that SqrR is a sensor of H 2 S-derived reactive sulfur species that maintain sulfide homeostasis in this photosynthetic bacterium and reveal the mechanism of sulfide-dependent transcriptional derepression of genes involved in sulfide metabolism.sulfide sensor | photosynthesis regulation | reactive sulfur species | purple bacteria | Rhodobacter T he discovery of ∼550 deep-sea hydrothermal vents more than 30 y ago (1) has led to the theory that energy metabolism in early ancestral organisms may have arisen from deep-sea hydrothermal vents where simple inorganic molecules such as hydrogen sulfide or hydrogen gas, as well as methane, exist (2-4). Such ancient energy metabolism has been assumed to be similar to that of extant chemolithotrophs, which obtain energy from these molecules. Indeed, various chemolithoautotrophic microbes thrive in deep-sea hydrothermal vents and are capable of oxidizing sulfides, methane, and/or hydrogen gas for use as energy sources and electron donors (5). Some photosynthetic bacteria have also been isolated from deep-sea hydrothermal vents that can grow photosynthetically using sulfide as an electron donor and geothermal radiation as an energy source instead of solar radiation (6), as hypothesized for ancestral phototrophs.Many purple photosynthetic bacteria have remarkable metabolic versatility required to meet the energy demands of sulfidedependent and -independent photosynthesis as well as aerobic and anaerobic respiration. These bacteria tightly control the synthesis of their electron transfer proteins involved in each growth mode in response to a specific electron donor, oxygen tension, and light intensity (7, 8). Among these regulatory systems, oxygen-and lightsensing mechanisms have been well-studied; however, mechanisms used to sen...
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