{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T02:36:17Z","timestamp":1785551777039,"version":"3.56.0"},"reference-count":103,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>\n                    Reactive sulfur species (RSS), which include various persulfides and polysulfides, are generated by multiple enzymes\n                    <jats:italic>in vivo<\/jats:italic>\n                    and play critical roles in mammalian physiological processes such as redox signaling, metabolic regulation, radical scavenging and anti-inflammatory responses. Cystathionine\n                    <jats:italic>\u03b2<\/jats:italic>\n                    -synthase (CBS), cystathionine\n                    <jats:italic>\u03b3<\/jats:italic>\n                    -lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3MST) are well known to mediate endogenous production of hydrogen sulfide (H\n                    <jats:sub>2<\/jats:sub>\n                    S), and, together with the mitochondrial isoform of cysteinyl-tRNA synthetase (CARS2), are proposed to be major sources of intracellular persulfides and polysulfides. In mitochondria, enzymes involved in the sulfide oxidation pathway, including sulfide:quinone oxidoreductase (SQOR), persulfide dioxygenase (ETHE1) and thiosulfate sulfurtransferase (TST), also contribute to maintaining and regulating intracellular persulfide levels. Selective inhibitors targeting these enzymes are expected to be powerful tools for elucidating the functions of RSS, as well as having therapeutic potential. In this review, we present a comprehensive overview of these enzymes, focusing on their reaction mechanisms and inhibitors.\n                  <\/jats:p>","DOI":"10.3389\/fphys.2026.1764165","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T05:22:04Z","timestamp":1770614524000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Enzymes that generate and regulate intracellular persulfides and polysulfides: mechanistic insights and inhibitors"],"prefix":"10.3389","volume":"17","author":[{"given":"Ko","family":"Hirabayashi","sequence":"first","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, Keio University","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eita","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, Keio University","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisashi","family":"Ohno","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, Keio University","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orie","family":"Takayama","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, Keio University","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sota","family":"Yamada","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, Keio University","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenjiro","family":"Hanaoka","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, Keio University","place":["Tokyo, Japan"]},{"name":"Human Biology-Microbiome-Quantum Research Center (WPI-Bio2Q), Keio University","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1111\/bph.14574","article-title":"3-Mercaptopyruvate sulfurtransferase supports endothelial cell angiogenesis and bioenergetics","volume":"177","author":"Abdollahi Govar","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"6124","DOI":"10.1021\/ja00799a053","article-title":"Acetylenic enzyme inactivators. Inactivation of gamma-cystathionase, in vitro and in vivo, by propargylglycine","volume":"95","author":"Abeles","year":"1973","journal-title":"J. Am. Chem. Soc."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1038\/s41467-017-01311-y","article-title":"Cysteinyl-tRNA synthetase governs cysteine polysulfidation and mitochondrial bioenergetics","volume":"8","author":"Akaike","year":"2017","journal-title":"Nat. Commun."},{"key":"B4","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1016\/j.freeradbiomed.2024.07.007","article-title":"New aspects of redox signaling mediated by supersulfides in health and disease","volume":"222","author":"Akaike","year":"2024","journal-title":"Free Radic. Biol. Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"5453","DOI":"10.1111\/bph.70141","article-title":"Effect of 3-mercaptopyruvate sulfurtransferase (3-MST) inhibitors on contractile responses in porcine coronary artery","volume":"182","author":"Almaheize","year":"2025","journal-title":"Br. J. Pharmacol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"9982","DOI":"10.3390\/ijms24129982","article-title":"Cystathionine \u03b3-lyase self-inactivates by polysulfidation during cystine metabolism","volume":"24","author":"Araki","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B7","doi-asserted-by":"publisher","first-page":"102331","DOI":"10.1016\/j.redox.2022.102331","article-title":"Emerging roles of cystathionine \u03b2-synthase in various forms of cancer","volume":"53","author":"Ascen\u00e7\u00e3o","year":"2022","journal-title":"Redox Biol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"102466","DOI":"10.1016\/j.redox.2022.102466","article-title":"Regulation of CyR61 expression and release by 3- mercaptopyruvate sulfurtransferase in colon cancer cells","volume":"56","author":"Ascen\u00e7\u00e3o","year":"","journal-title":"Redox Biol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1823","DOI":"10.3390\/antiox11091823","article-title":"Sequential accumulation of \u201cdriver\u201d pathway mutations induces the upregulation of hydrogen-sulfide-producing enzymes in human colonic epithelial cell organoids","volume":"11","author":"Ascen\u00e7\u00e3o","year":"","journal-title":"Antioxidants"},{"key":"B10","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1111\/bph.12171","article-title":"Selectivity of commonly used pharmacological inhibitors for cystathionine \u03b2 synthase (CBS) and cystathionine \u03b3 lyase (CSE)","volume":"169","author":"Asimakopoulou","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/biom10030447","article-title":"Role of 3-mercaptopyruvate sulfurtransferase in the regulation of proliferation, migration, and bioenergetics in murine colon cancer cells","volume":"10","author":"Augsburger","year":"2020","journal-title":"Biomolecules"},{"key":"B12","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.abb.2004.08.037","article-title":"Redox regulation and reaction mechanism of human cystathionine-beta-synthase: a PLP-dependent hemesensor protein","volume":"433","author":"Banerjee","year":"2005","journal-title":"Arch. Biochem. Biophys."},{"key":"B13","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/s1570-9639(03)00044-x","article-title":"Reaction mechanism and regulation of cystathionine beta-synthase","volume":"1647","author":"Banerjee","year":"2003","journal-title":"Biochim. Biophys. Acta"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/bph.16271","article-title":"Supersulfide biology and translational medicine for disease control","volume":"183","author":"Barayeu","year":"2023","journal-title":"Br. J. Pharmacol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"128443","DOI":"10.1016\/j.bmcl.2021.128443","article-title":"Synthesis and evaluation of potent novel inhibitors of human sulfide:quinone oxidoreductase","volume":"54","author":"Baugh","year":"2021","journal-title":"Bioorg Med. Chem. Lett."},{"key":"B16","doi-asserted-by":"publisher","first-page":"15466","DOI":"10.1074\/jbc.RA120.014728","article-title":"Acidity and nucleophilic reactivity of glutathione persulfide","volume":"295","author":"Benchoam","year":"2020","journal-title":"J. Biol. Chem."},{"key":"B17","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.freeradbiomed.2016.09.020","article-title":"The chemical biology of the persulfide (RSSH)\/perthiyl (RSS\u00b7) redox couple and possible role in biological redox signaling","volume":"101","author":"Bianco","year":"2016","journal-title":"Free Radic. Biol. Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1089\/ars.2010.3678","article-title":"Mitochondria and sulfide: a very old story of poisoning, feeding, and signaling?","volume":"15","author":"Bouillaud","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"B19","doi-asserted-by":"publisher","first-page":"8452","DOI":"10.3390\/ijms23158452","article-title":"Thiosulfate-cyanide sulfurtransferase a mitochondrial essential enzyme: from cell metabolism to the biotechnological applications","volume":"23","author":"Buonvino","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B20","doi-asserted-by":"publisher","first-page":"11601","DOI":"10.1074\/jbc.M808026200","article-title":"H2S biogenesis by human cystathionine \u03b3-Lyase leads to the novel sulfur metabolites lanthionine and homolanthionine and is responsive to the grade of hyperhomocysteinemia","volume":"284","author":"Chiku","year":"2009","journal-title":"J. Biol. Chem."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1483","DOI":"10.1016\/j.chembiol.2020.10.012","article-title":"Discovery of an inhibitor for bacterial 3-mercaptopyruvate sulfurtransferase that synergistically controls bacterial survival","volume":"27","author":"Croppi","year":"2020","journal-title":"Cell. Chem. Biol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"26866","DOI":"10.1074\/jbc.M115.672816","article-title":"Reaction of hydrogen sulfide with disulfide and sulfenic acid to form the strongly nucleophilic persulfide","volume":"290","author":"Cuevasanta","year":"2015","journal-title":"J. Biol. Chem."},{"key":"B23","doi-asserted-by":"publisher","first-page":"16456","DOI":"10.1038\/s41598-023-43536-6","article-title":"Discovery of a cystathionine \u03b3-lyase (CSE) selective inhibitor targeting active-site pyridoxal 5\u2019-phosphate (PLP) via schiff base formation","volume":"13","author":"Echizen","year":"2023","journal-title":"Sci. Rep."},{"key":"B24","doi-asserted-by":"publisher","first-page":"E3845","DOI":"10.1073\/pnas.1414545111","article-title":"Structural insight into the molecular mechanism of allosteric activation of human cystathionine \u03b2-synthase by S-adenosylmethionine","volume":"111","author":"Ere\u00f1o-Orbea","year":"2014","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B25","doi-asserted-by":"publisher","first-page":"34543","DOI":"10.1074\/jbc.M114.605733","article-title":"Characterization and interaction studies of two isoforms of the dual localized 3-mercaptopyruvate sulfurtransferase TUM1 from humans","volume":"289","author":"Fr\u00e4sdorf","year":"2014","journal-title":"J. Biol. Chem."},{"key":"B26","doi-asserted-by":"publisher","first-page":"e181299","DOI":"10.1172\/JCI181299","article-title":"Sulfite oxidase deficiency causes persulfidation loss and hydrogen sulfide release","volume":"135","author":"Fu","year":"2025","journal-title":"J. Clin. Invest"},{"key":"B27","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1111\/bph.14356","article-title":"Persulfide synthases that are functionally coupled with translation mediate sulfur respiration in Mammalian cells: persulfide synthases and sulfur respiration","volume":"176","author":"Fujii","year":"2019","journal-title":"Br. J. Pharmacol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"2140","DOI":"10.1002\/1873-3468.13090","article-title":"Biological hydropersulfides and related polysulfides \u2013 a new concept and perspective in redox biology","volume":"592","author":"Fukuto","year":"2018","journal-title":"FEBS Lett."},{"key":"B29","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1107\/s090744499701216x","article-title":"Structure of sulfur-substituted rhodanese at 1.36 \u00c5 resolution","volume":"54","author":"Gliubich","year":"1998","journal-title":"Acta Crystallogr. D."},{"key":"B30","doi-asserted-by":"publisher","first-page":"2183","DOI":"10.1212\/WNL.0000000000001055","article-title":"A homozygous splice-site mutation in CARS2 is associated with progressive myoclonic epilepsy","volume":"83","author":"Hallmann","year":"2014","journal-title":"Neurology"},{"key":"B31","doi-asserted-by":"publisher","first-page":"40227","DOI":"10.1038\/srep40227","article-title":"Discovery and mechanistic characterization of selective inhibitors of H2S-producing enzyme: 3-mercaptopyruvate sulfurtransferase (3MST) targeting active-site cysteine persulfide","volume":"7","author":"Hanaoka","year":"2017","journal-title":"Sci. Rep."},{"key":"B32","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1089\/ars.2022.0067","article-title":"A metabolic paradigm for hydrogen sulfide signaling via electron transport chain plasticity","volume":"38","author":"Hanna","year":"2023","journal-title":"Antioxid. Redox Signal."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1134","DOI":"10.1038\/nsmb849","article-title":"Shape-selective RNA recognition by cysteinyl-tRNA synthetase","volume":"11","author":"Hauenstein","year":"2004","journal-title":"Nat. Struct. Mol. Biol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/0167-4838(82)90499-x","article-title":"The specificity of active-site alkylation by iodoacetic acid in the enzyme thiosulfate sulfurtransferase","volume":"702","author":"Horowitz","year":"1982","journal-title":"Biochim. Biophys. Acta"},{"key":"B35","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1016\/j.jmb.2009.11.058","article-title":"Site-directed mutagenesis on human cystathionine-gamma-lyase reveals insights into the modulation of H2S production","volume":"396","author":"Huang","year":"2010","journal-title":"J. Mol. Biol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"BSR20221006","DOI":"10.1042\/BSR20221006","article-title":"Reactive sulfur species and their significance in health and disease","volume":"42","author":"Iciek","year":"2022","journal-title":"Biosci. Rep."},{"key":"B37","doi-asserted-by":"publisher","first-page":"7606","DOI":"10.1073\/pnas.1321232111","article-title":"Reactive cysteine persulfides and S-polythiolation regulate oxidative stress and redox signaling","volume":"111","author":"Ida","year":"2014","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B38","doi-asserted-by":"publisher","first-page":"6804","DOI":"10.1021\/bi300778t","article-title":"Human sulfide:quinone oxidoreductase catalyzes the first step in hydrogen sulfide metabolism and produces a sulfane sulfur metabolite","volume":"51","author":"Jackson","year":"2012","journal-title":"Biochemistry"},{"key":"B39","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1016\/j.str.2019.03.002","article-title":"X-ray structure of human sulfide:quinone oxidoreductase: insights into the mechanism of mitochondrial hydrogen sulfide oxidation","volume":"27","author":"Jackson","year":"2019","journal-title":"Structure"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1771","DOI":"10.1093\/cvr\/cvab206","article-title":"Discovery of a first-in-class inhibitor of sulfide:quinone oxidoreductase that protects against adverse cardiac remodelling and heart failure","volume":"118","author":"Jackson","year":"2022","journal-title":"Cardiovasc Res."},{"key":"B41","doi-asserted-by":"publisher","first-page":"10625","DOI":"10.1021\/bi010711p","article-title":"Regulation of human cystathionine beta-synthase by S-adenosyl-L-methionine: evidence for two catalytically active conformations involving an autoinhibitory domain in the C-terminal region","volume":"40","author":"Janos\u00edk","year":"2001","journal-title":"Biochemistry"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1402","DOI":"10.3390\/antiox13111402","article-title":"Persulfidation of human cystathionine \u03b3-lyase inhibits its activity: a negative feedback regulation mechanism for H2S production","volume":"13","author":"Jia","year":"2024","journal-title":"Antioxidants"},{"key":"B43","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1016\/j.bbrc.2016.10.022","article-title":"Protein polysulfidation-dependent persulfide dioxygenase activity of ethylmalonic encephalopathy protein 1","volume":"480","author":"Jung","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B44","doi-asserted-by":"publisher","first-page":"44561","DOI":"10.1074\/jbc.M112.407411","article-title":"Characterization of patient mutations in human persulfide dioxygenase (ETHE1) involved in H2S catabolism","volume":"287","author":"Kabil","year":"2012","journal-title":"J. Biol. Chem."},{"key":"B45","doi-asserted-by":"publisher","first-page":"12429","DOI":"10.1074\/jbc.RA118.004096","article-title":"Mechanism-based inhibition of human persulfide dioxygenase by \u03b3-glutamyl-homocysteinyl-glycine","volume":"293","author":"Kabil","year":"2018","journal-title":"J. Biol. Chem."},{"key":"B46","doi-asserted-by":"publisher","first-page":"111","DOI":"10.3164\/jcbn.20-124","article-title":"Regulation of redox signaling by reactive sulfur species","volume":"68","author":"Kasamatsu","year":"2021","journal-title":"J. Clin. Biochem. Nutr."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1721","DOI":"10.3390\/molecules21121721","article-title":"Redox signaling regulated by cysteine persulfide and protein polysulfidation","volume":"21","author":"Kasamatsu","year":"2016","journal-title":"Molecules"},{"key":"B48","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1007\/s00726-010-0510-x","article-title":"Hydrogen sulfide: its production, release and functions","volume":"41","author":"Kimura","year":"2011","journal-title":"Amino Acids"},{"key":"B49","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.niox.2014.01.002","article-title":"The physiological role of hydrogen sulfide and beyond","volume":"41","author":"Kimura","year":"2014","journal-title":"Nitric Oxide"},{"key":"B50","doi-asserted-by":"publisher","first-page":"131","DOI":"10.2183\/pjab.91.131","article-title":"Hydrogen sulfide and polysulfides as signaling molecules","volume":"91","author":"Kimura","year":"2015","journal-title":"Proc. Jpn. Acad. Ser. B"},{"key":"B51","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-017-11004-7","article-title":"3-Mercaptopyruvate sulfurtransferase produces potential redox regulators cysteine- and glutathione-persulfide (Cys-SSH and GSSH) together with signaling molecules H2S2, H2S3 and H2S","volume":"7","author":"Kimura","year":"2017","journal-title":"Sci. Rep."},{"key":"B52","doi-asserted-by":"publisher","first-page":"165716","DOI":"10.1016\/j.bbadis.2020.165716","article-title":"Unraveling the role of thiosulfate sulfurtransferase in metabolic diseases","volume":"1866","author":"Kruithof","year":"2020","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1645","DOI":"10.1016\/s1357-2725(03)00005-0","article-title":"Inhibition of the catalytic activity of rhodanese by S-nitrosylation using nitric oxide donors","volume":"35","author":"Kwiecie\u0144","year":"2003","journal-title":"Int. J. Biochem. Cell. Biol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"11641","DOI":"10.1074\/jbc.M117.788547","article-title":"H2S oxidation by nanodisc-embedded human sulfide quinone oxidoreductase","volume":"292","author":"Landry","year":"2017","journal-title":"J. Biol. Chem."},{"key":"B55","doi-asserted-by":"publisher","first-page":"1515","DOI":"10.1016\/j.chembiol.2019.09.010","article-title":"A catalytic trisulfide in human sulfide quinone oxidoreductase catalyzes coenzyme A persulfide synthesis and inhibits butyrate oxidation","volume":"26","author":"Landry","year":"2019","journal-title":"Cell. Chem. Biol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"14295","DOI":"10.1021\/jacs.0c06066","article-title":"Dismantling and rebuilding the trisulfide cofactor demonstrates its essential role in human sulfide quinone oxidoreductase","volume":"142","author":"Landry","year":"2020","journal-title":"J. Am. Chem. Soc."},{"key":"B57","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1002\/cbic.202000661","article-title":"Hydrogen sulfide oxidation by sulfide quinone oxidoreductase","volume":"22","author":"Landry","year":"2021","journal-title":"Chembiochem"},{"key":"B58","doi-asserted-by":"publisher","first-page":"1892","DOI":"10.1016\/S0021-9258(18)93525-8","article-title":"The mechanism of the rhodanese-catalyzed thiosulfate-cyanide reaction","volume":"243","author":"Leininger","year":"1968","journal-title":"J. Biol. Chem."},{"key":"B59","doi-asserted-by":"publisher","first-page":"30901","DOI":"10.1074\/jbc.M114.602664","article-title":"Organization of the human mitochondrial hydrogen sulfide oxidation pathway","volume":"289","author":"Libiad","year":"2014","journal-title":"J. Biol. Chem."},{"key":"B60","doi-asserted-by":"publisher","first-page":"23579","DOI":"10.1074\/jbc.M115.675694","article-title":"Polymorphic variants of human rhodanese exhibit differences in thermal stability and sulfur transfer kinetics","volume":"290","author":"Libiad","year":"2015","journal-title":"J. Biol. Chem."},{"key":"B61","doi-asserted-by":"publisher","first-page":"7010","DOI":"10.1021\/acscatal.6b01417","article-title":"Mechanism of the glutathione persulfide oxidation process catalyzed by ethylmalonic encephalopathy protein 1","volume":"6","author":"Lin","year":"2016","journal-title":"ACS Catal."},{"key":"B62","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/s40635-020-0296-4","article-title":"Emerging pharmacological tools to control hydrogen sulfide signaling in critical illness","volume":"8","author":"Marutani","year":"2020","journal-title":"Intensive Care Med. Exp."},{"key":"B63","doi-asserted-by":"publisher","first-page":"17582","DOI":"10.1073\/pnas.0407613101","article-title":"Menadione metabolism to thiodione in hepatoblastoma by scanning electrochemical microscopy","volume":"101","author":"Mauzeroll","year":"2004","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B64","doi-asserted-by":"publisher","first-page":"36018","DOI":"10.1074\/jbc.M114.610782","article-title":"Inter-domain communication of human cystathionine \u03b2-synthase: structural basis of S-adenosyl-L-methionine activation","volume":"289","author":"McCorvie","year":"2014","journal-title":"J. Biol. Chem."},{"key":"B65","doi-asserted-by":"publisher","first-page":"2931","DOI":"10.1038\/s41467-024-46864-x","article-title":"Architecture and regulation of filamentous human cystathionine beta-synthase","volume":"15","author":"McCorvie","year":"2024","journal-title":"Nat. Commun."},{"key":"B66","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1042\/BJ20110841","article-title":"Thioredoxin and dihydrolipoic acid are required for 3-mercaptopyruvate sulfurtransferase to produce hydrogen sulfide","volume":"439","author":"Mikami","year":"2011","journal-title":"Biochem. J."},{"key":"B67","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1016\/j.freeradbiomed.2023.09.020","article-title":"Targeting gamma-glutamyl transpeptidase: a pleiotropic enzyme involved in glutathione metabolism and in the control of redox homeostasis","volume":"208","author":"Mitri\u0107","year":"2023","journal-title":"Free Radic. Biol. Med."},{"key":"B68","doi-asserted-by":"publisher","first-page":"1219","DOI":"10.2174\/092986706776360914","article-title":"The mercaptopyruvate pathway in cysteine catabolism: a physiologic role and related disease of the multifunctional 3-mercaptopyruvate sulfurtransferase","volume":"13","author":"Nagahara","year":"2006","journal-title":"Curr. Med. Chem."},{"key":"B69","doi-asserted-by":"publisher","first-page":"2778","DOI":"10.1093\/emboj\/21.11.2778","article-title":"Structural origins of amino acid selection without editing by cysteinyl-tRNA synthetase","volume":"21","author":"Newberry","year":"2002","journal-title":"EMBO J."},{"key":"B70","doi-asserted-by":"publisher","first-page":"103018","DOI":"10.1016\/j.redox.2023.103018","article-title":"Longevity control by supersulfide-mediated mitochondrial respiration and regulation of protein quality","volume":"69","author":"Nishimura","year":"2024","journal-title":"Redox Biol."},{"key":"B71","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1089\/ars.2022.0191","article-title":"Actions of thiols, persulfides, and polysulfides as free radical scavenging antioxidants","volume":"39","author":"Noguchi","year":"2023","journal-title":"Antioxid. Redox Signal"},{"key":"B72","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1089\/ars.2023.0405","article-title":"Persulfide biosynthesis conserved evolutionarily in all organisms","volume":"39","author":"Ogata","year":"2023","journal-title":"Antioxid. Redox Signal"},{"key":"B73","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.freeradbiomed.2014.09.007","article-title":"Redox chemistry and chemical biology of H2S, hydropersulfides, and derived species: implications of their possible biological activity and utility","volume":"77","author":"Ono","year":"2014","journal-title":"Free Radic. Biol. Med."},{"key":"B74","doi-asserted-by":"publisher","first-page":"2237","DOI":"10.3390\/ijms26052237","article-title":"The selective 3-MST inhibitor I3MT-3 works as a potent caspase-1 inhibitor","volume":"26","author":"Otani","year":"2025","journal-title":"Int. J. Mol. Sci."},{"key":"B75","doi-asserted-by":"publisher","first-page":"172","DOI":"10.3390\/biom15020172","article-title":"The therapeutic potential of supersulfides in oxidative stress-related diseases","volume":"15","author":"Pan","year":"2025","journal-title":"Biomolecules"},{"key":"B76","doi-asserted-by":"publisher","first-page":"1775","DOI":"10.1039\/c5mb00216h","article-title":"Persulfides: current knowledge and challenges in chemistry and chemical biology","volume":"11","author":"Park","year":"2015","journal-title":"Mol. Biosyst."},{"key":"B77","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1515\/hsz-2020-0249","article-title":"3-Mercaptopyruvate sulfurtransferase: an enzyme at the crossroads of sulfane sulfur trafficking","volume":"402","author":"Pedre","year":"2021","journal-title":"Biol. Chem."},{"key":"B78","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1007\/s00018-022-04479-9","article-title":"H2S biogenesis by cystathionine beta-synthase: mechanism of inhibition by aminooxyacetic acid and unexpected role of serine","volume":"79","author":"Petrosino","year":"2022","journal-title":"Cell. Mol. Life Sci."},{"key":"B79","doi-asserted-by":"publisher","first-page":"2458","DOI":"10.1093\/hmg\/ddv007","article-title":"Crystal structure of human persulfide dioxygenase: structural basis of ethylmalonic encephalopathy","volume":"24","author":"Pettinati","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"B80","doi-asserted-by":"publisher","first-page":"6489","DOI":"10.1073\/pnas.0509531103","article-title":"S-adenosylmethionine stabilizes cystathionine beta-synthase and modulates redox capacity","volume":"103","author":"Prudova","year":"2006","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B81","doi-asserted-by":"publisher","first-page":"603","DOI":"10.3390\/antiox12030603","article-title":"Role of 3-mercaptopyruvate sulfurtransferase (3-MST) in physiology and disease","volume":"12","author":"Rao","year":"2023","journal-title":"Antioxidants"},{"key":"B82","doi-asserted-by":"publisher","first-page":"3884","DOI":"10.1111\/j.1742-4658.2008.06535.x","article-title":"Rhodanese-thioredoxin system and allyl sulfur compounds: implications in apoptosis induction","volume":"275","author":"Sabelli","year":"2008","journal-title":"FEBS J."},{"key":"B83","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/B978-0-443-18827-5.00010-8","article-title":"Chemical approaches to discover selective inhibitors of sulfurtransferases and transsulfuration enzymes","volume-title":"Sulfurtransferases: essential enzymes for life","author":"Sasaki","year":"2023"},{"key":"B84","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1111\/bph.14446","article-title":"Regulators of the transsulfuration pathway: modulating the transsulfuration pathway in disease","volume":"176","author":"Sbodio","year":"2019","journal-title":"Br. J. Pharmacol."},{"key":"B85","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1007\/s10545-009-9006-9","article-title":"Dealing with methionine\/homocysteine sulfur: cysteine metabolism to taurine and inorganic sulfur","volume":"34","author":"Stipanuk","year":"2011","journal-title":"J. Inherit. Metab. Dis."},{"key":"B86","doi-asserted-by":"publisher","first-page":"3076","DOI":"10.1074\/jbc.M805459200","article-title":"Structural basis for the inhibition mechanism of human cystathionine gamma-lyase, an enzyme responsible for the production of H2S","volume":"284","author":"Sun","year":"2009","journal-title":"J. Biol. Chem."},{"key":"B87","doi-asserted-by":"publisher","first-page":"102899","DOI":"10.1016\/j.redox.2023.102899","article-title":"How super is supersulfide? reconsidering persulfide reactivity in cellular biology","volume":"67","author":"Switzer","year":"2023","journal-title":"Redox Biol."},{"key":"B88","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1093\/intimm\/dxad057","article-title":"Regulation of innate immune and inflammatory responses by supersulfides","volume":"36","author":"Tsutsuki","year":"2024","journal-title":"Int. Immunol."},{"key":"B89","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1089\/ars.2023.0352","article-title":"Emerging chemical biology of protein persulfidation","volume":"39","author":"Vignane","year":"2023","journal-title":"Antioxid. Redox Signal"},{"key":"B90","doi-asserted-by":"publisher","first-page":"5465","DOI":"10.1016\/S0021-9258(18)91969-1","article-title":"Studies on the active site of rhodanese","volume":"243","author":"Wang","year":"1968","journal-title":"J. Biol. Chem."},{"key":"B91","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1038\/s41419-018-1063-2","article-title":"A pharmacological probe identifies cystathionine \u03b2-synthase as a new negative regulator for ferroptosis","volume":"9","author":"Wang","year":"2018","journal-title":"Cell. Death Dis."},{"key":"B92","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1146\/annurev.pa.24.040184.002315","article-title":"Cyanide intoxication and its mechanism of antagonism","volume":"24","author":"Way","year":"1984","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"B93","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1042\/CS20110267","article-title":"Emerging role of hydrogen sulfide in health and disease: critical appraisal of biomarkers and pharmacological tools","volume":"121","author":"Whiteman","year":"2011","journal-title":"Clin. Sci."},{"key":"B94","doi-asserted-by":"crossref","first-page":"407","DOI":"10.18388\/abp.2007_3263","article-title":"Menadione effect on l-cysteine desulfuration in U373 cells","volume":"54","author":"Wr\u00f3bel","year":"2007","journal-title":"Acta Biochim. Pol."},{"key":"B95","doi-asserted-by":"publisher","first-page":"102353","DOI":"10.1016\/j.cbpa.2023.102353","article-title":"Emergence of (hydro)persulfides as suppressors of lipid peroxidation and ferroptotic cell death","volume":"76","author":"Wu","year":"2023","journal-title":"Curr. Opin. Chem. Biol."},{"key":"B96","doi-asserted-by":"publisher","first-page":"43464","DOI":"10.1074\/jbc.M112.414722","article-title":"Detection of reaction intermediates during human cystathionine \u03b2-synthase-monitored turnover and H2S production","volume":"287","author":"Yadav","year":"2012","journal-title":"J. Biol. Chem."},{"key":"B97","doi-asserted-by":"publisher","first-page":"20002","DOI":"10.1074\/jbc.M113.466177","article-title":"Structure and kinetic analysis of H2S production by human mercaptopyruvate sulfurtransferase","volume":"288","author":"Yadav","year":"2013","journal-title":"J. Biol. Chem."},{"key":"B98","doi-asserted-by":"publisher","first-page":"11011","DOI":"10.1074\/jbc.RA119.009047","article-title":"S-3-Carboxypropyl-l-cysteine specifically inhibits cystathionine \u03b3-lyase-dependent hydrogen sulfide synthesis","volume":"294","author":"Yadav","year":"2019","journal-title":"J. Biol. Chem."},{"key":"B99","doi-asserted-by":"publisher","first-page":"6299","DOI":"10.1074\/jbc.RA120.012616","article-title":"Thioredoxin regulates human mercaptopyruvate sulfurtransferase at physiologically-relevant concentrations","volume":"295","author":"Yadav","year":"2020","journal-title":"J. Biol. Chem."},{"key":"B100","doi-asserted-by":"publisher","first-page":"1913","DOI":"10.1093\/oxfordjournals.jbchem.a133393","article-title":"The mechanism of the L-cystine cleavage reaction catalyzed by rat liver \u03b3-cystathionase","volume":"89","author":"Yamanishi","year":"1981","journal-title":"J. Biochem."},{"key":"B101","doi-asserted-by":"publisher","first-page":"868","DOI":"10.3390\/antiox12040868","article-title":"Synthesis of sulfides and persulfides is not impeded by disruption of three canonical enzymes in sulfur metabolism","volume":"12","author":"Zainol","year":"2023","journal-title":"Antioxidants"},{"key":"B102","doi-asserted-by":"publisher","first-page":"1355","DOI":"10.2741\/4286","article-title":"Regulation of cystathionine gamma-lyase\/H2S system and its pathological implication","volume":"19","author":"Zhao","year":"2014","journal-title":"Front. Biosci."},{"key":"B103","doi-asserted-by":"publisher","first-page":"697","DOI":"10.3390\/biom10050697","article-title":"Cystathionine-\u03b2-synthase: molecular regulation and pharmacological inhibition","volume":"10","author":"Zuhra","year":"2020","journal-title":"Biomolecules"}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2026.1764165\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T05:22:05Z","timestamp":1770614525000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2026.1764165\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,9]]},"references-count":103,"alternative-id":["10.3389\/fphys.2026.1764165"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2026.1764165","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,9]]},"article-number":"1764165"}}