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Significance: Hydrogen sulfide (H2S) has been recognized as a signaling molecule as well as a cytoprotectant. It modulates neurotransmission, regulates vascular tone, and protects various tissues and organs, including neurons, the heart, and kidneys, from oxidative stress and ischemia-reperfusion injury. H2S is produced from l-cysteine by cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3MST) along with cysteine aminotransferase. Recent Advances: In addition to these enzymes, we recently identified a novel pathway to produce H2S from d-cysteine, which involves d-amino acid oxidase (DAO) along with 3MST. These enzymes are localized in the cytoplasm, mitochondria, and peroxisomes. However, some enzymes translocate to organelles under specific conditions. Moreover, H2S-derived potential signaling molecules such as polysulfides and HSNO have been identified. Critical Issues: The physiological stimulations, which trigger the production of H2S and its derivatives and maintain their local levels, remain unclear. Future Directions: Understanding the regulation of the H2S production and H2S-derived signaling molecules and the specific stimuli that induce their release will provide new insights into the biology of H2S and therapeutic development in diseases involving these substances. Antioxid. Redox Signal. 22, 362-376. [ABSTRACT FROM AUTHOR]

Significance: Hydrogen sulfide (H2S) has been recognized as a physiological mediator with a variety of functions. It regulates synaptic transmission, vascular tone, inflammation, transcription, and angiogenesis; protects cells from oxidative stress and ischemia-reperfusion injury; and promotes healing of ulcers. Recent Advances: In addition to cystathionine β-synthase and cystathionine γ-lyase, 3-mercaptopyruvate sulfurtransferase along with cysteine aminotransferase was recently demonstrated to produce H2S. Even in bacteria, H2S produced by these enzymes functions as a defense against antibiotics, suggesting that the cytoprotective effect of H2S is a universal defense mechanism in organisms from bacteria to mammals. Critical Issues: The functional form of H2S-undissociated H2S gas, dissociated HS ion, or some other form of sulfur-has not been identified. Future Directions: The regulation of H2S production by three enzymes may lead to the identification of the physiological signals that are required to release H2S. The identification of the physiological functions of other forms of sulfur may also help understand the biological significance of H2S. Antioxid. Redox Signal. 20, 783-793. [ABSTRACT FROM AUTHOR]

It has been almost two decades since the first demonstration of hydrogen sulfide (H2S) as a physiological mediator of cognitive function and vascular tone. H2S is physiologically important because it protects various organs from ischemia-reperfusion injury besides regulating inflammation, oxygen sensing, cell growth, and senescence. The production, metabolism, and regulation of H2S have been studied extensively. H2S modulates target proteins through sulfhydration (or sulfuration) or by the reduction of cysteine disulfide bonds. A large number of novel H2S-donating compounds are being developed owing to the therapeutic potential of H2S. Recently, polysulfides, rather than H2S, have been identified as molecules that sulfhydrate (or sulfurate) their target proteins. Antioxid. Redox Signal. 22, 347-349. [ABSTRACT FROM AUTHOR]