Implications of differential peroxyl radical-induced inactivation of glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase for the pentose phosphate pathway

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dc.article.number21191
dc.catalogadorjwg
dc.contributor.authorReyes Valenzuela, Juan Sebastián
dc.contributor.authorFigueroa Alegría, Juan David
dc.contributor.authorMartínez Rojas, Francisco Javier
dc.contributor.authorLópez Alarcon, Camilo Ignacio
dc.contributor.authorFuentes Lemus, Eduardo Felipe
dc.contributor.authorHagglund, P.M.
dc.contributor.authorDavies, Michael J.
dc.contributor.authorFierro Huerta, Angelica María
dc.contributor.authorArenas, Felipe
dc.date.accessioned2025-01-02T18:20:27Z
dc.date.available2025-01-02T18:20:27Z
dc.date.issued2022
dc.description.abstract© 2022, The Author(s).Escherichia coli glucose-6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6PGDH) are key enzymes of the pentose phosphate pathway, responsible for the NADPH production in cells. We investigated modification of both enzymes mediated by peroxyl radicals (ROO·) to determine their respective susceptibilities to and mechanisms of oxidation. G6PDH and 6PGDH were incubated with AAPH (2,2?-azobis(2-methylpropionamidine)dihydrochloride), which was employed as ROO· source. The enzymatic activities of both enzymes were determined by NADPH release, with oxidative modifications examined by electrophoresis and liquid chromatography (LC) with fluorescence and mass (MS) detection. The activity of G6PDH decreased up to 62.0 ± 15.0% after 180 min incubation with 100 mM AAPH, whilst almost total inactivation of 6PGDH was determined under the same conditions. Although both proteins contain abundant Tyr (particularly 6PGDH), these residues were minimally affected by ROO·, with Trp and Met being major targets. LC–MS and in silico analysis showed that the modification sites of G6PDH are distant to the active site, consistent with a dispersed distribution of modifications, and inactivation resulting from oxidation of multiple Trp and Met residues. In contrast, the sites of oxidation detected on 6PGDH are located close to its catalytic site indicating a more localized oxidation, and a consequent high susceptibility to ROO·-mediated inactivation.
dc.description.funderFONDEQUIP
dc.description.funderEuropean Union’s Horizon 2020 research and innovation programme
dc.description.funderFondecyt
dc.description.funderNovo Nordisk Foundation
dc.fuente.origenORCID
dc.identifier.doi10.1038/s41598-022-25474-x
dc.identifier.eissn20452322
dc.identifier.issn20452322
dc.identifier.pubmedid36476946
dc.identifier.scopusidSCOPUS_ID:85143555859
dc.identifier.urihttps://www.nature.com/srep/
dc.identifier.urihttps://doi.org/10.1038/s41598-022-25474-x
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/89461
dc.information.autorucEscuela de Química; Fuentes Lemus, Eduardo Felipe; 0000-0002-1465-8466; 186720
dc.information.autorucEscuela de Química; Reyes Valenzuela Juan Sebastian; S/I; 1268701
dc.information.autorucEscuela de Química; Figueroa Alegria Juan David; S/I; 1071087
dc.information.autorucEscuela de Química; Martinez Rojas Francisco Javier; 0000-0001-9701-0528; 186659
dc.information.autorucEscuela de Química; Fierro Huerta Angelica Maria; 0000-0002-6507-4188; 218137
dc.issue.numero1
dc.language.isoen
dc.nota.accesocontenido completo
dc.publisherNature Research
dc.relation.ispartofScientific Reports
dc.revistaScientific Reports
dc.rightsacceso restringido
dc.subject.ddc570
dc.subject.deweyBiologíaes_ES
dc.titleImplications of differential peroxyl radical-induced inactivation of glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase for the pentose phosphate pathway
dc.typeartículo
dc.volumen12
sipa.codpersvinculados186720
sipa.codpersvinculados1268701
sipa.codpersvinculados1071087
sipa.codpersvinculados186659
sipa.codpersvinculados218137
sipa.trazabilidadORCID;2024-12-23
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