2024
Glutathione synthesis in the mouse liver supports lipid abundance through NRF2 repression
Asantewaa G, Tuttle E, Ward N, Kang Y, Kim Y, Kavanagh M, Girnius N, Chen Y, Rodriguez K, Hecht F, Zocchi M, Smorodintsev-Schiller L, Scales T, Taylor K, Alimohammadi F, Duncan R, Sechrist Z, Agostini-Vulaj D, Schafer X, Chang H, Smith Z, O’Connor T, Whelan S, Selfors L, Crowdis J, Gray G, Bronson R, Brenner D, Rufini A, Dirksen R, Hezel A, Huber A, Munger J, Cravatt B, Vasiliou V, Cole C, DeNicola G, Harris I. Glutathione synthesis in the mouse liver supports lipid abundance through NRF2 repression. Nature Communications 2024, 15: 6152. PMID: 39034312, PMCID: PMC11271484, DOI: 10.1038/s41467-024-50454-2.Peer-Reviewed Original ResearchConceptsGlutamate-cysteine ligase catalytic subunitLipid abundanceLipogenic enzyme expressionAbundance in vivoLipid productionCatalytic subunitRepress Nrf2Transcription factorsNrf2 repressionAdult tissuesSynthesis of GSHEnzyme expressionNon-redundantRedox bufferMouse liverLoss of GSHTriglyceride productionIn vivo modelsAbundanceGlutathione synthesisLiver balanceFat storesOxidative stressLipidDeletion
2022
Glutathione-dependent redox balance characterizes the distinct metabolic properties of follicular and marginal zone B cells
Franchina DG, Kurniawan H, Grusdat M, Binsfeld C, Guerra L, Bonetti L, Soriano-Baguet L, Ewen A, Kobayashi T, Farinelle S, Minafra AR, Vandamme N, Carpentier A, Borgmann FK, Jäger C, Chen Y, Kleinewietfeld M, Vasiliou V, Mittelbronn M, Hiller K, Lang PA, Brenner D. Glutathione-dependent redox balance characterizes the distinct metabolic properties of follicular and marginal zone B cells. Nature Communications 2022, 13: 1789. PMID: 35379825, PMCID: PMC8980022, DOI: 10.1038/s41467-022-29426-x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB-LymphocytesGlutamate-Cysteine LigaseGlutathioneLymphoid TissueMiceOxidation-ReductionConceptsElectron transport chainMarginal zone B cellsMitochondrial electron transport chainGlutamate-cysteine ligaseCatalytic subunitRedox controlCell-specific ablationRedox balanceTransport chainMetabolic dependenciesCysteine ligaseProtein synthesisMetabolite succinateMTOR activationGlutathione synthesisATP levelsMetabolic propertiesB cellsMetabolic principlesMetabolic featuresDistinct metabolic propertiesMZBCellsActivationLigaseOxidative stress induces inflammation of lens cells and triggers immune surveillance of ocular tissues
Thompson B, Davidson EA, Chen Y, Orlicky DJ, Thompson DC, Vasiliou V. Oxidative stress induces inflammation of lens cells and triggers immune surveillance of ocular tissues. Chemico-Biological Interactions 2022, 355: 109804. PMID: 35123994, PMCID: PMC9136680, DOI: 10.1016/j.cbi.2022.109804.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcysteineAnimalsButhionine SulfoximineCell LineChemokine CCL7CytokinesDown-RegulationEpithelial CellsEpithelial-Mesenchymal TransitionEyeGlutamate-Cysteine LigaseImmunity, InnateLens, CrystallineLeukocytesMiceMice, Inbred C57BLMice, KnockoutOxidative StressReactive Oxygen SpeciesUp-RegulationConceptsPosterior capsule opacificationCytokine expressionKO miceImmune surveillanceOxidative stressLens epithelial cellsOcular structuresLens cellsDevelopment of PCOEpithelial cellsInnate immune cellsExpression of cytokinesEx vivo inductionOcular surface tissuesExpression of markersImmune response genesCON miceControl miceCapsule opacificationImmune cellsPostnatal dayΑ-SMAMouse modelOcular tissuesVivo induction
2019
Glutathione deficiency-elicited reprogramming of hepatic metabolism protects against alcohol-induced steatosis
Chen Y, Manna SK, Golla S, Krausz KW, Cai Y, Garcia-Milian R, Chakraborty T, Chakraborty J, Chatterjee R, Thompson DC, Gonzalez FJ, Vasiliou V. Glutathione deficiency-elicited reprogramming of hepatic metabolism protects against alcohol-induced steatosis. Free Radical Biology And Medicine 2019, 143: 127-139. PMID: 31351176, PMCID: PMC6848780, DOI: 10.1016/j.freeradbiomed.2019.07.025.Peer-Reviewed Original ResearchMeSH KeywordsAcetyl Coenzyme AAlcohol DrinkingAMP-Activated Protein KinasesAnimalsEthanolFatty AcidsFatty LiverGlucuronic AcidGlutamate-Cysteine LigaseGlutamatesGlutathioneHomeostasisLipogenesisLiverMaleMiceMice, Inbred C57BLMice, KnockoutOligonucleotide Array Sequence AnalysisOxidation-ReductionOxidative StressPentose Phosphate PathwayProtective AgentsTranscription, GeneticConceptsGlutamate-cysteine ligase modifier subunit geneProtein kinase pathwayAcetyl-CoA fluxMultiple cellular pathwaysAlcohol-induced steatosisCellular stressNucleotide biosynthesisLiver microarray analysisGlobal profilingSubunit geneCellular pathwaysMetabolic reprogrammingKinase pathwayMicroarray analysisMolecular mechanismsGSH poolCellular responsesMetabolic pathwaysLower GSHMolecular pathwaysMetabolic homeostasisAmino acidsDepletion of glutathioneCritical pathogenic eventGlucuronate pathwayHepatic metabolic adaptation in a murine model of glutathione deficiency
Chen Y, Golla S, Garcia-Milian R, Thompson DC, Gonzalez FJ, Vasiliou V. Hepatic metabolic adaptation in a murine model of glutathione deficiency. Chemico-Biological Interactions 2019, 303: 1-6. PMID: 30794799, PMCID: PMC6743730, DOI: 10.1016/j.cbi.2019.02.015.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDisease Models, AnimalFatty LiverGlutamate-Cysteine LigaseGlutathioneHomeostasisLiverMetabolomicsMiceMice, KnockoutOxidation-ReductionConceptsCellular non-protein thiolsMetabolic adaptationGlutamate-cysteine ligase modifier subunitNon-protein thiolsHepatic metabolic adaptationCellular redoxGlobal profilingGSH homeostasisModifier subunitLiver developmentBiochemical mechanismsMetabolic homeostasisAmino acidsGclm null miceDefense mechanismsEnvironmental insultsOxidative damageFatty liver developmentNull miceSpectrum of changesNucleic acidsMetabolic signaturesPivotal roleHomeostasisGlutathione deficiency
2018
Glutathione de novo synthesis but not recycling process coordinates with glutamine catabolism to control redox homeostasis and directs murine T cell differentiation
Lian G, Gnanaprakasam JR, Wang T, Wu R, Chen X, Liu L, Shen Y, Yang M, Yang J, Chen Y, Vasiliou V, Cassel TA, Green DR, Liu Y, Fan TW, Wang R. Glutathione de novo synthesis but not recycling process coordinates with glutamine catabolism to control redox homeostasis and directs murine T cell differentiation. ELife 2018, 7: e36158. PMID: 30198844, PMCID: PMC6152796, DOI: 10.7554/elife.36158.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationCell ProliferationDimethyl FumarateGlutamate-Cysteine LigaseGlutamineGlutathioneGlutathione DisulfideHomeostasisLymphocyte ActivationMice, Inbred C57BLOxidation-ReductionOxidative StressReactive Oxygen SpeciesReceptors, Antigen, T-CellTh17 CellsT-LymphocytesT-Lymphocytes, RegulatoryConceptsCell fateDe novo synthesisNovo synthesisCell differentiationT cell differentiationMurine T cell differentiationT cell fateGlutamate-cysteine ligaseLineage choiceRedox demandsGlutathione de novo synthesisRecycling pathwayInhibition of GSHRedox homeostasisGSH biosynthesisGlutamine catabolismRedox balanceModifier subunitEssential precursorIntracellular GSHEssential roleGlutathione disulfideDifferentiationGSH contentGSH
2017
Glutathione Primes T Cell Metabolism for Inflammation
Mak TW, Grusdat M, Duncan GS, Dostert C, Nonnenmacher Y, Cox M, Binsfeld C, Hao Z, Brüstle A, Itsumi M, Jäger C, Chen Y, Pinkenburg O, Camara B, Ollert M, Bindslev-Jensen C, Vasiliou V, Gorrini C, Lang PA, Lohoff M, Harris IS, Hiller K, Brenner D. Glutathione Primes T Cell Metabolism for Inflammation. Immunity 2017, 46: 675-689. PMID: 28423341, DOI: 10.1016/j.immuni.2017.03.019.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsEncephalomyelitis, Autoimmune, ExperimentalEnergy MetabolismGlutamate-Cysteine LigaseGlutamineGlutathioneGlycolysisImmunoblottingInflammationMice, Inbred C57BLMice, KnockoutNFATC Transcription FactorsProto-Oncogene Proteins c-mycReactive Oxygen SpeciesSignal TransductionT-LymphocytesTOR Serine-Threonine KinasesConceptsReactive oxygen speciesMYC transcription factorsConditional gene targetingT cell-specific ablationGlutamate-cysteine ligaseT cell metabolismRapamycin 1Catalytic subunitMetabolic integrationTranscription factorsGene targetingMetabolic reprogrammingBiosynthetic requirementsUnexpected roleExpression of NFATAntiviral defenseCysteine ligaseCell metabolismGSH pathwayMammalian targetGSH productionMurine TGSH deficiencyOxygen speciesCell effector functions
2013
Glutathione defense mechanism in liver injury: Insights from animal models
Chen Y, Dong H, Thompson DC, Shertzer HG, Nebert DW, Vasiliou V. Glutathione defense mechanism in liver injury: Insights from animal models. Food And Chemical Toxicology 2013, 60: 38-44. PMID: 23856494, PMCID: PMC3801188, DOI: 10.1016/j.fct.2013.07.008.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsLiver injuryGlutamate-cysteine ligaseMouse modelLiver disease processTransgenic mouse modelCellular GSH concentrationGSH homeostasisLiver diseaseClinical stageHepatic insultLiver pathologyDisease processRate-limiting enzymeAnimal modelsHepatic GSHHepatic responseModifier subunitGenetic deficiencyInjuryPathophysiological functionsGSH deficitThiol antioxidantGSH concentrationMiceRole of GSH
2012
Effect of chronic glutathione deficiency on the behavioral phenotype of Gclm(−/−) knockout mice
Chen Y, Curran CP, Nebert DW, Patel KV, Williams MT, Vorhees CV. Effect of chronic glutathione deficiency on the behavioral phenotype of Gclm(−/−) knockout mice. Neurotoxicology And Teratology 2012, 34: 450-457. PMID: 22580179, PMCID: PMC3404268, DOI: 10.1016/j.ntt.2012.04.009.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornBrainBrain ChemistryDisease Models, AnimalFemaleGlutamate-Cysteine LigaseGlutathioneMaleMiceMice, Inbred C57BLMice, KnockoutOxidative StressConceptsGlutamate-cysteine ligase modifier subunitMorris water mazeKO miceKnockout miceWater mazeOxidative stressChronic glutathione deficiencyPostnatal day 60Novel object recognitionWild-type littermatesTime of conceptionChronic GSH depletionChronic oxidative stressOpen-field activityKnockout mouse lineNormal spatial learningControl brain regionsAcoustic startleBehavioral abnormalitiesPostnatal lifeBrain regionsNeurodegenerative disordersDay 60Phenotyping testsMice
2011
Glutathione-Deficient Mice Are Susceptible to TCDD-Induced Hepatocellular Toxicity but Resistant to Steatosis
Chen Y, Krishan M, Nebert DW, Shertzer HG. Glutathione-Deficient Mice Are Susceptible to TCDD-Induced Hepatocellular Toxicity but Resistant to Steatosis. Chemical Research In Toxicology 2011, 25: 94-100. PMID: 22082335, DOI: 10.1021/tx200242a.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAspartate AminotransferasesEnvironmental PollutantsFatty LiverFemaleGamma-GlutamyltransferaseGene Expression RegulationGlutamate-Cysteine LigaseGlutathioneLipid MetabolismLiverMiceMice, Inbred C57BLMice, KnockoutNon-alcoholic Fatty Liver DiseaseOligonucleotide Array Sequence AnalysisPolychlorinated DibenzodioxinsReverse Transcriptase Polymerase Chain ReactionConceptsTetrachlorodibenzo-p-dioxinGlutamic oxaloacetic transaminaseGlutamate-cysteine ligaseHepatocellular toxicityPlasma glutamic oxaloacetic transaminaseWild-type female miceImpaired lipid metabolismTissue GSH levelsTCDD-induced hepatotoxicityGlutathione-deficient miceΓ-glutamyl transferaseHepatocellular injuryWT miceHepatocellular damageLipid metabolism genesFemale miceWT littermatesTransgenic miceCDNA microarray expression analysisDe novo GSH biosynthesisOxaloacetic transaminaseLipid metabolismConsecutive daysSteatosisMiceLipid metabolism and body composition in Gclm(−/−) mice
Kendig EL, Chen Y, Krishan M, Johansson E, Schneider SN, Genter MB, Nebert DW, Shertzer HG. Lipid metabolism and body composition in Gclm(−/−) mice. Toxicology And Applied Pharmacology 2011, 257: 338-348. PMID: 21967773, PMCID: PMC3226854, DOI: 10.1016/j.taap.2011.09.017.Peer-Reviewed Original ResearchConceptsHigh-fat dietExcessive weight gainInsulin resistanceWeight gainFatty liverBasal metabolic rateGlutamate-cysteine ligase modifier subunit geneDecreased respiratory quotientExcess body weightIntestinal lipid absorptionHepatic oxidative stress responseDietary energy consumptionWild-type controlsGlucose intoleranceOxidative stress responseFat dietNormal dietRisk factorsBody compositionBody weightMetabolic rateDietary lipidsLipid absorptionMetabolic diseasesExperimental animals
2010
Oral N-acetylcysteine rescues lethality of hepatocyte-specific Gclc-knockout mice, providing a model for hepatic cirrhosis
Chen Y, Johansson E, Yang Y, Miller ML, Shen D, Orlicky DJ, Shertzer HG, Vasiliou V, Nebert DW, Dalton TP. Oral N-acetylcysteine rescues lethality of hepatocyte-specific Gclc-knockout mice, providing a model for hepatic cirrhosis. Journal Of Hepatology 2010, 53: 1085-1094. PMID: 20810184, PMCID: PMC2970663, DOI: 10.1016/j.jhep.2010.05.028.Peer-Reviewed Original ResearchAcetylcysteineAdministration, OralAnimalsAntioxidantsBase SequenceCytokinesDisease Models, AnimalDNA PrimersGene Expression ProfilingGlutamate-Cysteine LigaseGlutathioneHepatocytesLiverLiver CirrhosisMiceMice, KnockoutMicroscopy, Electron, TransmissionMitochondria, LiverOxidative StressRNA, MessengerGlutathione deficient C57BL/6J mice are not sensitized to ozone-induced lung injury
Johansson E, Wesselkamper SC, Shertzer HG, Leikauf GD, Dalton TP, Chen Y. Glutathione deficient C57BL/6J mice are not sensitized to ozone-induced lung injury. Biochemical And Biophysical Research Communications 2010, 396: 407-412. PMID: 20417186, PMCID: PMC2892220, DOI: 10.1016/j.bbrc.2010.04.105.Peer-Reviewed Original ResearchConceptsOzone-induced lung injuryGlutamate-cysteine ligase modifier subunitLung injuryLung hyperpermeabilityDegree of neutrophiliaBronchoalveolar lavage fluidWild-type miceInflammatory gene expressionPulmonary susceptibilityLavage fluidCompensatory augmentationKnockout miceTotal protein concentrationPpm ozoneMiceModifier subunitMRNA levelsAntioxidant defenseMember 2Antioxidant glutathioneMetallothionein-1GSH depletionHyperpermeabilityInjuryAntioxidant responseRedox Dysregulation Affects the Ventral But Not Dorsal Hippocampus: Impairment of Parvalbumin Neurons, Gamma Oscillations, and Related Behaviors
Steullet P, Cabungcal JH, Kulak A, Kraftsik R, Chen Y, Dalton TP, Cuenod M, Q. K. Redox Dysregulation Affects the Ventral But Not Dorsal Hippocampus: Impairment of Parvalbumin Neurons, Gamma Oscillations, and Related Behaviors. Journal Of Neuroscience 2010, 30: 2547-2558. PMID: 20164340, PMCID: PMC6634545, DOI: 10.1523/jneurosci.3857-09.2010.Peer-Reviewed Original Research8-Hydroxy-2'-DeoxyguanosineAdaptation, OcularAnalysis of VarianceAnimalsAnimals, NewbornBehavior, AnimalBiological ClocksCalbindin 2CalbindinsConditioning, ClassicalDeoxyguanosineElectric StimulationElectroencephalographyExcitatory Amino Acid AgonistsExploratory BehaviorFearFeeding BehaviorGene Expression RegulationGene Expression Regulation, DevelopmentalGlutamate-Cysteine LigaseGlutathioneHippocampusInterneuronsKainic AcidMaleMaze LearningMiceMice, Inbred C57BLMice, KnockoutNeural PathwaysOxidation-ReductionOxidative StressParvalbuminsPattern Recognition, VisualRewardS100 Calcium Binding Protein GSpatial Behavior
2009
Early onset senescence occurs when fibroblasts lack the glutamate–cysteine ligase modifier subunit
Chen Y, Johansson E, Fan Y, Shertzer HG, Vasiliou V, Nebert DW, Dalton TP. Early onset senescence occurs when fibroblasts lack the glutamate–cysteine ligase modifier subunit. Free Radical Biology And Medicine 2009, 47: 410-418. PMID: 19427898, PMCID: PMC2773044, DOI: 10.1016/j.freeradbiomed.2009.05.003.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcysteineAnimalsBeta-GalactosidaseCell Culture TechniquesCell CycleCell Growth ProcessesCellular SenescenceCyclin-Dependent Kinase Inhibitor p21DNA DamageFemaleFetusFibroblastsFree Radical ScavengersGlutamate-Cysteine LigaseGlutathioneMiceMice, Inbred C57BLMice, KnockoutPregnancyProtein SubunitsReactive Oxygen SpeciesTumor Suppressor Protein p53ConceptsGlutamate-cysteine ligasePremature senescenceCellular redox environmentCellular antioxidant glutathionePrimary murine fibroblastsSenescence-associated beta-galactosidase activityCell cycle arrestInduction of p53Beta-galactosidase activityPrevents premature senescenceCatalytic subunitCellular senescenceGrowth arrestGlutamate cysteine ligase modifierModifier subunitP21 proteinPhysiological roleSenescenceDNA damageRedox environmentCycle arrestMurine fibroblastsGSH synthesisN-acetylcysteine increasesPrimary cellsCurcumin, quercetin, and tBHQ modulate glutathione levels in astrocytes and neurons: importance of the glutamate cysteine ligase modifier subunit
Lavoie S, Chen Y, Dalton TP, Gysin R, Cuénod M, Steullet P, Q. K. Curcumin, quercetin, and tBHQ modulate glutathione levels in astrocytes and neurons: importance of the glutamate cysteine ligase modifier subunit. Journal Of Neurochemistry 2009, 108: 1410-1422. PMID: 19183254, DOI: 10.1111/j.1471-4159.2009.05908.x.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceAnimalsAntioxidantsAstrocytesCell SurvivalCells, CulturedCerebral CortexCurcuminDose-Response Relationship, DrugEmbryo, MammalianEnzyme InhibitorsGene ExpressionGlutamate-Cysteine LigaseGlutathioneHydroquinonesMiceMice, Inbred C57BLMice, KnockoutNeuronsProtein SubunitsQuercetinUp-RegulationConceptsGlutamate-cysteine ligaseGCL activityRate-limiting synthesizing enzymeRedox regulatorCatalytic subunitGSH levelsGene expressionCysteine ligaseGlutamate cysteine ligase modifierModifier subunitCell deathCell typesGSH synthesisEnzymeNeurodegenerative diseasesCultured neuronsGCLMSubunitsMRNA levelsSynthesizing enzymesGSHLower GSHAbility of curcuminExpressionLigase
2007
Oxidative and electrophilic stress induces multidrug resistance–associated protein transporters via the nuclear factor‐E2–related factor‐2 transcriptional pathway
Maher JM, Dieter MZ, Aleksunes LM, Slitt AL, Guo G, Tanaka Y, Scheffer GL, Chan JY, Manautou JE, Chen Y, Dalton TP, Yamamoto M, Klaassen CD. Oxidative and electrophilic stress induces multidrug resistance–associated protein transporters via the nuclear factor‐E2–related factor‐2 transcriptional pathway. Hepatology 2007, 46: 1597-1610. PMID: 17668877, DOI: 10.1002/hep.21831.Peer-Reviewed Original ResearchMeSH Keywords5' Flanking RegionAnimalsAntioxidantsButylated HydroxyanisoleCell Line, TumorFluorescent Antibody Technique, IndirectGene Expression RegulationGlutamate-Cysteine LigaseGlutathioneHepatocytesLiverMiceMice, Inbred C57BLMice, KnockoutMultidrug Resistance-Associated ProteinsNF-E2-Related Factor 2Oxidative StressPromoter Regions, GeneticPyrazinesReverse Transcriptase InhibitorsThionesThiophenesConceptsTranscriptional pathwaysBinding of Nrf2Nrf2 transcriptional pathwayNrf2 target genesMarked geneAdenosine triphosphate-dependent transportersChromatin immunoprecipitationElectrophilic stressNuclear Nrf2 levelsTarget genesRegulatory pathwaysCoordinated inductionPromoter regionProtein transportersMultidrug resistance-associated proteinNrf2-null miceResponse elementResistance-associated proteinHepa1c1c7 cellsProtein inductionFactor 2 (Nrf2) activatorQuinone oxidoreductase 1MRP transportersTransportersNrf2 levelsHepatocyte‐specific Gclc deletion leads to rapid onset of steatosis with mitochondrial injury and liver failure
Chen Y, Yang Y, Miller ML, Shen D, Shertzer HG, Stringer KF, Wang B, Schneider SN, Nebert DW, Dalton TP. Hepatocyte‐specific Gclc deletion leads to rapid onset of steatosis with mitochondrial injury and liver failure. Hepatology 2007, 45: 1118-1128. PMID: 17464988, DOI: 10.1002/hep.21635.Peer-Reviewed Original ResearchConceptsLiver failureMitochondrial injuryLiver biochemistry testsSevere parenchymal damageNumerous liver diseasesMonths of ageGCLC geneHepatic failureLiver injuryParenchymal damageLiver diseaseDepletion of glutathioneHepatic steatosisHistological featuresGSH synthesisHepatic functionPostnatal dayHepatocyte deathKnockout miceRapid onsetBiochemistry testsHepatic GSHSteatosisUltrastructural examinationOxidative stressInteraction between the catalytic and modifier subunits of glutamate-cysteine ligase
Yang Y, Chen Y, Johansson E, Schneider SN, Shertzer HG, Nebert DW, Dalton TP. Interaction between the catalytic and modifier subunits of glutamate-cysteine ligase. Biochemical Pharmacology 2007, 74: 372-381. PMID: 17517378, DOI: 10.1016/j.bcp.2007.02.003.Peer-Reviewed Original ResearchMeSH KeywordsCatalysisCatalytic DomainDimerizationGlutamate-Cysteine LigaseGlutathioneProtein SubunitsSaccharomyces cerevisiaeStructure-Activity RelationshipTwo-Hybrid System TechniquesConceptsGlutamate-cysteine ligaseHeterodimer formationEnzyme structure-function relationshipsTwo-hybrid systemGlutathione biosynthesis pathwayPrimary amino acid sequenceC-terminal regionAmino acid sequenceN-terminal regionStructure-function relationshipsBiosynthesis pathwayRegulatory subunitCatalytic subunitDeletion analysisRate-limiting enzymeTertiary structureModifier subunitAmino acidsPoint mutationsSubunitsGCLCGSH inhibitionLigaseEnzyme activityGCLM
2005
Glutamate Cysteine Ligase Catalysis DEPENDENCE ON ATP AND MODIFIER SUBUNIT FOR REGULATION OF TISSUE GLUTATHIONE LEVELS*
Chen Y, Shertzer HG, Schneider SN, Nebert DW, Dalton TP. Glutamate Cysteine Ligase Catalysis DEPENDENCE ON ATP AND MODIFIER SUBUNIT FOR REGULATION OF TISSUE GLUTATHIONE LEVELS*. Journal Of Biological Chemistry 2005, 280: 33766-33774. PMID: 16081425, DOI: 10.1074/jbc.m504604200.Peer-Reviewed Original Research