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Hydrogen Sulfide Chemical Biology: Pathophysiological Roles and Detection


Hydrogen Sulfide Chemical Biology: Pathophysiological Roles and Detection

Gopi K Kolluru et al. Nitric Oxide.


Hydrogen sulfide (H2S) is the most recent endogenous gasotransmitter that has been reported to serve many physiological and pathological functions in different tissues. Studies over the past decade have revealed that H2S can be synthesized through numerous pathways and its bioavailability regulated through its conversion into different biochemical forms. H2S exerts its biological effects in various manners including redox regulation of protein and small molecular weight thiols, polysulfides, thiosulfate/sulfite, iron-sulfur cluster proteins, and anti-oxidant properties that affect multiple cellular and molecular responses. However, precise measurement of H2S bioavailability and its associated biochemical and pathophysiological roles remains less well understood. In this review, we discuss recent understanding of H2S chemical biology, its relationship to tissue pathophysiological responses and possible therapeutic uses.

Keywords: Cardiovascular; Cysteine; Nitric oxide; Oxidative stress; Sulfide.


Figure 1
Figure 1. Enzymatic and non-enzymatic synthesis of H2S and its metabolism
Enzymatic synthesis of H2S involves three enzymes in the mammalian systems, Cystathionine β-synthase (CBS), Cystathionine γ-lyase (CGL or CSE) and 3-mercaptopyruvate sulfurtransferase (MST) to form H2S. Non-enzymatic synthesis occurs through glucose, glutathione and polysulfides. H2S further metabolized into thiocyanate, methanethiol and thiosulfate catalyzed by rhodanese, bisulfide methyltransferase (BMT) and thiosulfate reductase (TSR) enzymes respectively. Thiosulfate can oxidize to sulfite through thiosulfate sulfurtransferase (TSST) and subsequently to sulfate. H2S reacts with hemoglobin to form sulfhemoglobin and with proteins in the tissues in the form of bound sulfur pool.
Figure 2
Figure 2. Storage and release of H2S and factors involved
H2S can be interconverted between gaseous and other complex storage compounds involving various factors like pH, oxidation, reduction, hydrogenation, and alkalization, microorganisms like sulfate reducing bacteria (SRB), apart from enzymatic catalyses through CSE, CBS, 3MST, sulfite reductase α-sub unit (CysJ), anaerobic sulfide reductase A (AsrA).
Figure 3
Figure 3. Interactions of H2S and NO signaling pathways
H2S and NO have common signaling that include upstream molecules like VEGF, HIF-1α, AKT, eNOS and XO mediated nitrite reduction to NO under ischemia; downstream signaling involves cGMP/PKG, Ras/Raf and MEK/ERK pathways leading to vascular remodeling. NO and H2S possibly react chemically to form novel compounds like S-nitrosothiol (SNO), nitroxyl (HNO), simple form of S-nitrosothiol (HSNO) and sulfinyl nitrite FS(O)NO.

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