{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T01:16:23Z","timestamp":1790471783897,"version":"4.1.0"},"reference-count":71,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,4,21]],"date-time":"2022-04-21T00:00:00Z","timestamp":1650499200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Oxidation of glyceraldehyde\u22123\u2212phosphate dehydrogenase (GAPDH) by reactive oxygen species such as H2O2 activate pleiotropic signaling pathways is associated with pathophysiological cell fate decisions. Oxidized GAPDH binds chaperone proteins with translocation of the complex to the nucleus and mitochondria initiating autophagy and cellular apoptosis. In this study, we establish the mechanism by which H2O2\u2212oxidized GAPDH subunits undergo a subunit conformational rearrangement. H2O2 oxidizes both the catalytic cysteine and a vicinal cysteine (four residues downstream) to their respective sulfenic acids. A \u2018two\u2212cysteine switch\u2019 is activated, whereby the sulfenic acids irreversibly condense to an intrachain thiosulfinic ester resulting in a major metastable subunit conformational rearrangement. All four subunits of the homotetramer are uniformly and independently oxidized by H2O2, and the oxidized homotetramer is stabilized at low temperatures. Over time, subunits unfold forming disulfide\u2212linked aggregates with the catalytic cysteine oxidized to a sulfinic acid, resulting from thiosulfinic ester hydrolysis via the highly reactive thiosulfonic ester intermediate. Molecular Dynamic Simulations provide additional mechanistic insights linking GAPDH subunit oxidation with generating a putative signaling conformer. The low\u2212temperature stability of the H2O2\u2212oxidized subunit conformer provides an operable framework to study mechanisms associated with gain\u2212of\u2212function activities of oxidized GAPDH to identify novel targets for the treatment of neurodegenerative diseases.<\/jats:p>","DOI":"10.3390\/ijms23094604","type":"journal-article","created":{"date-parts":[[2022,4,22]],"date-time":"2022-04-22T05:07:22Z","timestamp":1650604042000},"page":"4604","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Mechanism of GAPDH Redox Signaling by H2O2 Activation of a Two\u2212Cysteine Switch"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4831-1313","authenticated-orcid":false,"given":"Paul A.","family":"Hyslop","sequence":"first","affiliation":[{"name":"Arkley Research Labs, Arkley BioTek, LLC, 4444 Decatur Blvd., Indianapolis, IN 46241, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael O.","family":"Chaney","sequence":"additional","affiliation":[{"name":"Eli Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/0891-5849(95)00005-I","article-title":"Hydrogen peroxide as a potent bacteriostatic antibiotic: Implications for host defense","volume":"19","author":"Hyslop","year":"1995","journal-title":"Free Radic. Biol. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1517\/13543784.5.8.1013","article-title":"Section Review Anti\u2212infectives: Natural mediators of host\u2212defence: The role of H2O2 in the regulation of bacteriostasis","volume":"5","author":"Hyslop","year":"1996","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/0006-8993(94)01291-O","article-title":"Measurement of striatal H2O2 by microdialysis following global forebrain ischemia and reperfusion in the rat: Correlation with the cytotoxic potential of H2O2 in vitro","volume":"671","author":"Hyslop","year":"1995","journal-title":"Brain Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/0006-8993(93)91110-E","article-title":"A cellular model of oxidant\u2212mediated neuronal injury","volume":"615","author":"Hinshaw","year":"1993","journal-title":"Brain Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1038\/ncb2114","article-title":"GAPDH mediates nitrosylation of nuclear proteins","volume":"12","author":"Kornberg","year":"2010","journal-title":"Nat. Cell Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"26562","DOI":"10.1074\/jbc.M704199200","article-title":"The Active Site Cysteine of the Proapoptotic Protein Glyceraldehyde\u22123\u2212phosphate Dehydrogenase Is Essential in Oxidative Stress\u2212induced Aggregation and Cell Death","volume":"282","author":"Nakajima","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"11669","DOI":"10.1073\/pnas.94.21.11669","article-title":"Glyceraldehyde\u22123\u2212phosphate dehydrogenase: Nuclear translocation participates in neuronal and nonneuronal cell death","volume":"94","author":"Sawa","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1242\/jcs.114.9.1643","article-title":"Potential role of nuclear translocation of glyceraldehyde\u22123\u2212phosphate dehydrogenase in apoptosis and oxidative stress","volume":"114","author":"Dastoor","year":"2001","journal-title":"J. Cell Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1038\/ncb1747","article-title":"Nitric oxide\u2212induced nuclear GAPDH activates p300\/CBP and mediates apoptosis","volume":"10","author":"Sen","year":"2008","journal-title":"Nat. Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1515\/hsz-2014-0295","article-title":"Cytosolic thiol switches regulating basic cellular functions: GAPDH as an information hub?","volume":"396","author":"Hildebrandt","year":"2015","journal-title":"Biol. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Lazarev, V.F., Guzhova, I.V., and Margulis, B.A. (2020). Glyceraldehyde\u22123\u2212phosphate Dehydrogenase is a Multifaceted Therapeutic Target. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12050416"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Tossounian, M.A., Zhang, B., and Gout, I. (2020). The Writers, Readers, and Erasers in Redox Regulation of GAPDH. Antioxidants, 9.","DOI":"10.20944\/preprints202012.0024.v1"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Butera, G., Mullappilly, N., Masetto, F., Palmieri, M., Scupoli, M.T., Pacchiana, R., and Donadelli, M. (2019). Regulation of Autophagy by Nuclear GAPDH and Its Aggregates in Cancer and Neurodegenerative Disorders. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20092062"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1046\/j.1471-4159.2003.01755.x","article-title":"Hydrogen peroxide induces association between glyceraldehyde 3\u2212phosphate dehydrogenase and phospholipase D2 to facilitate phospholipase D2 activation in PC12 cells","volume":"85","author":"Kim","year":"2003","journal-title":"J. Neurochem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1007\/s00726-021-02959-z","article-title":"The role of posttranslational modification in moonlighting glyceraldehyde\u22123\u2212phosphate dehydrogenase structure and function","volume":"53","author":"Sirover","year":"2021","journal-title":"Amino Acids"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"369","DOI":"10.3233\/JAD-2010-1375","article-title":"Oxidatively modified glyceraldehyde\u22123\u2212phosphate dehydrogenase (GAPDH) and Alzheimer\u2019s disease: Many pathways to neurodegeneration","volume":"20","author":"Butterfield","year":"2010","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1080\/10409238.2020.1787325","article-title":"Moonlighting glyceraldehyde\u22123\u2212phosphate dehydrogenase: Posttranslational modification, protein and nucleic acid interactions in normal cells and in human pathology","volume":"55","author":"Sirover","year":"2020","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.arr.2018.09.003","article-title":"Oxidatively modified glyceraldehyde\u22123\u2212phosphate dehydrogenase in neurodegenerative processes and the role of low molecular weight compounds in counteracting its aggregation and nuclear translocation","volume":"48","author":"Gerszon","year":"2018","journal-title":"Ageing Res. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.ijbiomac.2019.01.064","article-title":"Glycation of alpha\u2212synuclein amplifies the binding with glyceraldehyde\u22123\u2212phosphate dehydrogenase","volume":"127","author":"Semenyuk","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3019","DOI":"10.1007\/s11033-020-05364-z","article-title":"The amyloid precursor protein affects glyceraldehyde 3\u2212phosphate dehydrogenase levels, organelle localisation and thermal stability","volume":"47","author":"Delport","year":"2020","journal-title":"Mol. Biol. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"134641","DOI":"10.1016\/j.neulet.2019.134641","article-title":"Nuclear accumulation of GAPDH, GluA2 and p53 in post\u2212mortem substantia nigral region of patients with Parkinson\u2019s disease","volume":"716","author":"Sekar","year":"2020","journal-title":"Neurosci. Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.neuroscience.2021.06.035","article-title":"GAPDH siRNA Regulates SH\u2212SY5Y Cell Apoptosis Induced by Exogenous alpha\u2212Synuclein Protein","volume":"469","author":"Ping","year":"2021","journal-title":"Neuroscience"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Tsai, C.W., Tsai, C.F., Lin, K.H., Chen, W.J., Lin, M.S., Hsieh, C.C., and Lin, C.C. (2020). An investigation of the correlation between the S\u2212glutathionylated GAPDH levels in blood and Alzheimer\u2019s disease progression. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0233289"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6329041","DOI":"10.1155\/2021\/6329041","article-title":"Identification of the Hub Genes in Alzheimer\u2019s Disease","volume":"2021","author":"Gui","year":"2021","journal-title":"Comput. Math. Methods Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1007\/s10571-006-9011-6","article-title":"Nitric Oxide\u2212GAPDH\u2212Siah: A Novel Cell Death Cascade","volume":"26","author":"Hara","year":"2006","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_26","first-page":"671","article-title":"Cerebral ischemia\u2212reperfusion induces GAPDH S\u2212nitrosylation and nuclear translocation","volume":"77","author":"Li","year":"2012","journal-title":"Biochemistry"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4727","DOI":"10.1074\/jbc.M116.759084","article-title":"Glyceraldehyde\u22123\u2212phosphate Dehydrogenase (GAPDH) Aggregation Causes Mitochondrial Dysfunction during Oxidative Stress\u2212induced Cell Death","volume":"292","author":"Nakajima","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Muronetz, V.I., Medvedeva, M.V., Sevostyanova, I.A., and Schmalhausen, E.V. (2021). Modification of Glyceraldehyde\u22123\u2212Phosphate Dehydrogenase with Nitric Oxide: Role in Signal Transduction and Development of Apoptosis. Biomolecules, 11.","DOI":"10.3390\/biom11111656"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/S0021-9258(19)78208-8","article-title":"The mechanism of inactivation of glyceraldehyde 3\u2212phosphate dehydrogenase by tetrathionate, o\u2212iodosobenzoate, and iodine monochloride","volume":"244","author":"Parker","year":"1969","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/0005-2744(75)90033-9","article-title":"The conversion of glyceraldehyde\u22123\u2212phosphate dehydrogenase to an acylphosphatase by trinitroglycerin and inactivation of this activity by azide and ascorbate","volume":"384","author":"You","year":"1975","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_31","first-page":"19","article-title":"Immunoblot detection of proteins that contain cysteine sulfinic or sulfonic acids with antibodies specific for hyperoxidized cysteine\u2212containing sequences","volume":"4","author":"Woo","year":"2010","journal-title":"Methods Redox Signal."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1042\/BJ20090854","article-title":"Oxidative modifications of glyceraldehyde\u22123\u2212phosphate dehydrogenase play a key role in its multiple cellular functions","volume":"423","author":"Hwang","year":"2009","journal-title":"Biochem. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"M110.000513","DOI":"10.1074\/mcp.M110.000513","article-title":"Novel oxidative modifications in redox\u2212active cysteine residues","volume":"10","author":"Jeong","year":"2011","journal-title":"Mol. Cell. Proteom."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1038\/nchembio.1720","article-title":"A proton relay enhances H2O2 sensitivity of GAPDH to facilitate metabolic adaptation","volume":"11","author":"Peralta","year":"2015","journal-title":"Nat. Chem. Biol."},{"key":"ref_35","first-page":"114","article-title":"Partial catalytic Cys oxidation of human GAPDH to Cys\u2212sulfonic acid","volume":"5","author":"Lia","year":"2020","journal-title":"Wellcome Open Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1107\/S0907444905042289","article-title":"High\u2212resolution structure of human D\u2212glyceraldehyde\u22123\u2212phosphate dehydrogenase","volume":"62","author":"Jenkins","year":"2006","journal-title":"Acta Crystallogr. Sect. D Biol. Crystallogr."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"129560","DOI":"10.1016\/j.bbagen.2020.129560","article-title":"S\u2212glutathionylation of human glyceraldehyde\u22123\u2212phosphate dehydrogenase and possible role of Cys152\u2212Cys156 disulfide bridge in the active site of the protein","volume":"1864","author":"Barinova","year":"2020","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/BF00926576","article-title":"Regulation of the activity of glyceraldehyde 3\u2212phosphate dehydrogenase by glutathione and H2O2","volume":"129","author":"Vaidyanathan","year":"1993","journal-title":"Mol. Cell. Biochem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"30632","DOI":"10.1074\/jbc.M801401200","article-title":"Human Glyceraldehyde\u22123\u2212phosphate Dehydrogenase Plays a Direct Role in Reactivating Oxidized Forms of the DNA Repair Enzyme APE1","volume":"283","author":"Azam","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1093\/abbs\/gmp026","article-title":"Immunoaffinity purification and characterization of glyceraldehyde\u22123\u2212phosphate dehydrogenase from human erythrocytes","volume":"41","author":"Mountassif","year":"2009","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2207","DOI":"10.1016\/j.bbapap.2010.09.002","article-title":"Recombinant human sperm\u2212specific glyceraldehyde\u22123\u2212phosphate dehydrogenase: Structural basis for enhanced stability","volume":"1804","author":"Elkina","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1039\/p29730001547","article-title":"Kinetics of the reaction of hydrogen peroxide with cysteine and cysteamine","volume":"11","author":"Barton","year":"1973","journal-title":"J. Chem. Soc. Perkin Trans. II"},{"key":"ref_43","first-page":"1","article-title":"Glyceraldehyde\u22123\u2212phosphate dehydrogenase","volume":"Volume Chapter 1","author":"Boyer","year":"1976","journal-title":"The Enzymes"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1021\/tx700168z","article-title":"Reactive sulfur species: Kinetics and mechanism of the hydrolysis of cysteine thiosulfinate ester","volume":"20","author":"Nagy","year":"2007","journal-title":"Chem. Res. Toxicol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1006\/abio.1998.2924","article-title":"A spectrophotometric assay for allicin and alliinase (Alliin lyase) activity: Reaction of 2\u2212nitro\u22125\u2212thiobenzoate with thiosulfinates","volume":"265","author":"Miron","year":"1998","journal-title":"Anal. Biochem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1073\/pnas.0813167106","article-title":"Detergent binding explains anomalous SDS\u2212PAGE migration of membrane proteins","volume":"106","author":"Rath","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/adsc.201900864","article-title":"Thiosulfonates as Emerging Reactants: Synthesis and Applications","volume":"362","author":"Mampuys","year":"2019","journal-title":"Adv. Synth. Catal."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/S0076-6879(02)48634-X","article-title":"Quantitation of protein sulfinic and sulfonic acid, irreversibly oxidized protein cysteine sites in cellular proteins","volume":"348","author":"Hamann","year":"2002","journal-title":"Methods Enzymol."},{"key":"ref_49","first-page":"67","article-title":"Hydrogen peroxide produced by Lactobacillus species as a regulatory molecule for vaginal microflora","volume":"56","author":"Strus","year":"2004","journal-title":"Med. Do\u015bwiadczalna Mikrobiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1111\/j.1574-695X.2006.00120.x","article-title":"The in vitro effect of hydrogen peroxide on vaginal microbial communities","volume":"48","author":"Strus","year":"2006","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1021\/bi701520y","article-title":"Reactivity of sulfenic acid in human serum albumin","volume":"47","author":"Turell","year":"2008","journal-title":"Biochemistry"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1021\/bi00831a039","article-title":"The reactivity of the sulfhydryl groups of lobster muscle glyceraldehyde 3\u2212phosphate dehydrogenase","volume":"8","author":"Wassarman","year":"1969","journal-title":"Biochemistry"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1016\/S0021-9258(19)77928-9","article-title":"Mechanisms of oxidant\u2212mediated cell injury. The glycolytic and mitochondrial pathways of ADP phosphorylation are major intracellular targets inactivated by hydrogen peroxide","volume":"263","author":"Hyslop","year":"1988","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1002\/psc.843","article-title":"The sequence TGAAKAVALVL from glyceraldehyde\u22123\u2212phosphate dehydrogenase displays structural ambivalence and interconverts between alpha\u2212helical and beta\u2212hairpin conformations mediated by collapsed conformational states","volume":"13","author":"Patel","year":"2007","journal-title":"J. Pept. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3405","DOI":"10.1073\/pnas.0511316103","article-title":"Mutant Huntingtin: Nuclear translocation and cytotoxicity mediated by GAPDH","volume":"103","author":"Bae","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/S0959-440X(00)00194-9","article-title":"Steered molecular dynamics and mechanical functions of proteins","volume":"11","author":"Isralewitz","year":"2001","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2","DOI":"10.3410\/B5-2","article-title":"Protein flexibility, not disorder, is intrinsic to molecular recognition","volume":"5","author":"Janin","year":"2013","journal-title":"F1000 Biol. Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.patbio.2014.08.002","article-title":"Glyceraldehyde\u22123\u2212phosphate dehydrogenase (GAPDH) and Alzheimer\u2019s disease","volume":"62","author":"Slassi","year":"2014","journal-title":"Pathol. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.freeradbiomed.2015.12.025","article-title":"Small molecules preventing GAPDH aggregation are therapeutically applicable in cell and rat models of oxidative stress","volume":"92","author":"Lazarev","year":"2016","journal-title":"Free Radic. Biol. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"26057","DOI":"10.1073\/pnas.1914484116","article-title":"Glutathionylation primes soluble glyceraldehyde\u22123\u2212phosphate dehydrogenase for late collapse into insoluble aggregates","volume":"116","author":"Zaffagnini","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.14336\/AD.2020.1230","article-title":"Extracellular GAPDH Promotes Alzheimer Disease Progression by Enhancing Amyloid\u2212beta Aggregation and Cytotoxicity","volume":"12","author":"Lazarev","year":"2021","journal-title":"Aging Dis."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Cyrne, L., Antunes, F., Sousa\u2212Lopes, A., Diaz\u2212Berrio, J., and Marinho, H.S. (2010). Glyceraldehyde\u22123\u2212phosphate dehydrogenase is largely unresponsive to low regulatory levels of hydrogen peroxide in Saccharomyces cerevisiae. BMC Biochem., 11.","DOI":"10.1186\/1471-2091-11-49"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4908","DOI":"10.1073\/pnas.83.13.4908","article-title":"Hydrogen peroxide\u2212induced injury of cells and its prevention by inhibitors of poly(ADP\u2212ribose) polymerase","volume":"83","author":"Schraufstatter","year":"1986","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3167","DOI":"10.1016\/j.bbagen.2017.09.008","article-title":"S\u2212glutathionylation of glyceraldehyde\u22123\u2212phosphate dehydrogenase induces formation of C150\u2212C154 intrasubunit disulfide bond in the active site of the enzyme","volume":"1861","author":"Barinova","year":"2017","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1172\/JCI112126","article-title":"Alterations in adenosine triphosphate and energy charge in cultured endothelial and P388D1 cells after oxidant injury","volume":"76","author":"Spragg","year":"1985","journal-title":"J. Clin. Investig."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/S0021-9258(19)52325-0","article-title":"Phosphate binding and the glyceraldehyde\u22123\u2212phosphate dehydrogenase reaction","volume":"203","author":"Velick","year":"1953","journal-title":"J. Biol. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/0003-9861(59)90090-6","article-title":"Tissue sulfhydryl groups","volume":"82","author":"Ellman","year":"1959","journal-title":"Arch Biochem. Biophys."},{"key":"ref_68","unstructured":"Atkins, P., Atkins, P.W., and de Paula, J. (2006). The rates of chemical reactions. Atkins\u2019 Physical Chemistry, W.H. Freeman. [8th ed.]."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/0003-2697(84)90786-3","article-title":"Sensitive quantitative analysis of disulfide bonds in polypeptides and proteins","volume":"138","author":"Thannhauser","year":"1984","journal-title":"Anal. Biochem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1055\/s-2006-960087","article-title":"HPLC analysis of allicin and other thiosulfinates in garlic clove homogenates","volume":"57","author":"Lawson","year":"1991","journal-title":"Planta Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1002\/jcc.20933","article-title":"The generalized Born\/volume integral implicit solvent model: Estimation of the free energy of hydration using London dispersion instead of atomic surface area","volume":"29","author":"Labute","year":"2008","journal-title":"J. Comput. Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/9\/4604\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:58:24Z","timestamp":1760137104000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/9\/4604"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,21]]},"references-count":71,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["ijms23094604"],"URL":"https:\/\/doi.org\/10.3390\/ijms23094604","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,21]]}}}