GLUTATHIONE AND SULFUR AMINO ACIDS IN HUMAN HEALTH AND DISEASE Editedby ROBERTA MASELLA GIUSEPPE MAZZA GLUTATHIONE AND SULFUR AMINO ACIDS IN HUMAN HEALTH AND DISEASE GLUTATHIONE AND SULFUR AMINO ACIDS IN HUMAN HEALTH AND DISEASE Editedby ROBERTA MASELLA GIUSEPPE MAZZA Copyright#2009byJohnWiley&Sons,Inc.Allrightsreserved PublishedbyJohnWiley&Sons,Inc.,Hoboken,NewJersey PublishedsimultaneouslyinCanada Nopartofthispublicationmaybereproduced,storedinaretrievalsystem,ortransmittedinanyformor byanymeans,electronic,mechanical,photocopying,recording,scanning,orotherwise,exceptaspermitted underSection107or108ofthe1976UnitedStatesCopyrightAct,withouteitherthepriorwritten permissionofthePublisher,orauthorizationthroughpaymentoftheappropriateper-copyfeetothe CopyrightClearanceCenter,Inc.,222RosewoodDrive,Danvers,MA01923,(978)750-8400,fax(978) 750-4470,oronthewebatwww.copyright.com.RequeststothePublisherforpermissionshouldbe addressedtothePermissionsDepartment,JohnWiley&Sons,Inc.,111RiverStreet,Hoboken,NJ07030, (201)748-6011,fax(201)748-6008,oronlineathttp://www.wiley.com/go/permission. LimitofLiability/DisclaimerofWarranty:Whilethepublisherandauthorhaveusedtheirbesteffortsin preparingthisbook,theymakenorepresentationsorwarrantieswithrespecttotheaccuracyorcompleteness ofthecontentsofthisbookandspecificallydisclaimanyimpliedwarrantiesofmerchantabilityorfitness foraparticularpurpose.Nowarrantymaybecreatedorextendedbysalesrepresentativesorwrittensales materials.Theadviceandstrategiescontainedhereinmaynotbesuitableforyoursituation.Youshould consultwithaprofessionalwhereappropriate.Neitherthepublishernorauthorshallbeliableforanyloss ofprofitoranyothercommercialdamages,includingbutnotlimitedtospecial,incidental,consequential, orotherdamages. Forgeneralinformationonourotherproductsandservicesorfortechnicalsupport,pleasecontactour CustomerCareDepartmentwithintheUnitedStatesat(800)762-2974,outsidetheUnitedStatesat (317)572-3993orfax(317)572-4002. Wileyalsopublishesitsbooksinvarietyofelectronicformats.Somecontentthatappearsinprintmay notbeavailableinelectronicformat.FormoreinformationaboutWileyproducts,visitourwebsiteat www.wiley.com. LibraryofCongressCataloging-in-PublicationData Masella,Roberta. Glutathioneandsulfuraminoacidsinhumanhealthanddisease/RobertaMasella,GiuseppeMazza. p.cm. Includesindex. ISBN978-0-470-17085-4(cloth) 1. Glutathione. 2. Sulfuraminoacids. I. Mazza,Giuseppe. II. Title. QP552.G58M372009 612.3098—dc22 2009011739 PrintedintheUnitedStatesofAmerica 10 9 8 7 6 5 4 3 2 1 CONTENTS PREFACE xv CONTRIBUTORS xix I INTRODUCTION 1 1 GLUTATHIONEANDTHESULFUR-CONTAINING AMINOACIDS:ANOVERVIEW 3 JohnT.BrosnanandMargaretE.Brosnan 1.1 Introduction / 3 1.2 WhySulfur-ContainingAminoAcids? / 4 1.3 S-Adenosylmethionine,Nature’sWonderCofactor / 7 1.4 Glutathione / 10 1.5 Taurine—theSecondEssentialSulfur-ContainingAminoAcid? / 13 1.6 Conclusions / 15 Acknowledgments / 15 References / 15 II CHEMISTRY AND METABOLISM OF GSH AND SULFUR AMINO ACIDS 19 2 SULFURAMINOACIDSCONTENTSOFDIETARYPROTEINS: DAILYINTAKEANDREQUIREMENTS 21 Ce´cileBos,Jean-Franc¸oisHuneau,andClaireGaudichon 2.1 Introduction / 21 2.2 SulfurAminoAcids(SAA)ContentofDietaryProtein / 21 2.3 SulfurAminoAcidIntake / 24 v vi CONTENTS 2.4 NutritionalRequirementforTotalSulfurAminoAcids / 24 2.5 Conclusions / 29 References / 30 3 CELLULARCOMPARTMENTALIZATIONOF GLUTATHIONE 35 FedericoV.Pallardo´,JelenaMarkovic,andJose´ Vin˜a 3.1 Introduction / 35 3.2 GlutathioneContentinCells / 36 References / 42 4 INTESTINALMETABOLISMOFSULFURAMINOACIDS 47 NancyBenight,DouglasG.Burrin,andBarbaraStoll 4.1 Introduction / 47 4.2 IsotopicApproachestoStudyMetabolism / 49 4.3 EvidenceofGutSulfurAminoAcidMetabolism / 50 4.4 OtherKeyPlayersinIntestinalSulfurAminoAcid Metabolism / 53 4.5 CysteineinRedoxFunctionandOxidantStress intheGut / 58 4.6 PathophysiologyofSulfurAminoAcidMetabolism intheGIT / 59 4.7 Conclusions / 64 References / 65 5 HEPATICSULFURAMINOACIDMETABOLISM 73 KevinL.Schalinske 5.1 Introduction / 73 5.2 DietaryRelationbetweenMethionineandCysteine / 73 5.3 MetabolicRelationbetweenHepaticSulfurAminoAcids, BVitamins,andMethylGroupMetabolism / 75 5.4 RegulationofSulfurAminoAcidMetabolismandRelated MetabolicPathwaysintheLiver / 77 5.5 ImpactofPhysiologicandNutritionalFactorsonSulfur AminoAcidMetabolism / 81 5.6 Conclusions / 84 References / 84 CONTENTS vii III ANTIOXIDANT AND DETOXIFICATION ACTIVITIES 91 6 GLUTATHIONEANDSULFURCONTAINING AMINOACIDS:ANTIOXIDANTAND CONJUGATIONACTIVITIES 93 Nils-ErikHuseby,ElisabethSundkvist,andGunbjørgSvineng 6.1 Introduction / 93 6.2 ReactiveOxygenSpeciesandAntioxidants / 94 6.3 GlutathioneRedoxCycle / 98 6.4 RegulationofGSHandCysteineLevels / 102 6.5 Biotransformation / 106 6.6 ROS-MediatedCellularSignaling / 109 6.7 TranscriptionRegulationofAntioxidantand ConjugationEnzymes / 110 6.8 OxidativeStressandDiseases / 111 References / 113 7 GLUTAREDOXINANDTHIOREDOXINENZYMESYSTEMS: CATALYTICMECHANISMSANDPHYSIOLOGICAL FUNCTIONS 121 ElizabethA.SabensandJohnJ.Mieyal 7.1 Introduction / 121 7.2 GeneralCharacteristicsofGlutaredoxins / 124 7.3 GeneralCharacteristicsofThioredoxins / 126 7.4 GlutaredoxinMechanismofAction / 128 7.5 ThioredoxinMechanismofAction / 132 7.6 ControlofGrxExpression / 133 7.7 ControlofTrxExpressioninMammalian Systems / 134 7.8 CellularFunctionsofGrx / 135 7.9 CellularFunctionsofTrx / 139 7.10 ReversibleSulfhydrylOxidationand Disease / 142 7.11 Conclusions / 145 References / 146 viii CONTENTS 8 METHIONINESULFOXIDEREDUCTASES:APROTECTIVE SYSTEMAGAINSTOXIDATIVEDAMAGE 157 HerbertWeissbachandNathanBrot 8.1 Introduction / 157 8.2 HistoryoftheMsrSystem / 158 8.3 MsrAandMsrBProteinStructureandMechanismofAction / 160 8.4 MsrReducingRequirement / 162 8.5 OtherMembersoftheMsrFamily / 165 8.6 TheMsrSystem:BothaRepairEnzymeanda ScavengerofROS / 166 8.7 GeneticStudiesontheRoleoftheMsrSysteminProtecting CellsAgainstOxidativeDamage / 167 8.8 EvidencethatOxidativeDamageisaMajorFactorinAging: RoleofMitochondriaandtheMsrSystem / 170 8.9 HowcantheMsrSystembeUtilizedforDrugDevelopment? / 174 8.10 MethionineSulfoxideandDisease / 176 Acknowledgment / 180 References / 181 IV BIOACTIVITY OF GSH AND SULFUR AMINO ACIDS AS REGULATORS OF CELLULAR PROCESSES 189 9 REGULATIONOFPROTEINFUNCTIONBY GLUTATHIONYLATION 191 PietroGhezziandPaoloDiSimplicio 9.1 Introduction / 191 9.2 GlutathioneandRedoxRegulationinImmunity / 192 9.3 ProteinCysteineOxidation / 193 9.4 MechanismsforPSSGFormationandtheComplex ScenarioofProteinGlutathionylation / 196 9.5 Deglutathionylation / 199 9.6 IdentificationofProteinsUndergoing Glutathionylation / 200 9.7 FunctionalConsequencesofProteinGlutathionylation / 202 9.8 StructuralChangesInducedbyProteinGlutathionylation / 203 9.9 Conclusions / 203 References / 203