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THE MOLECULAR NUTRITION OF AMINO ACIDS AND PROTEINS This pageintentionallyleftblank THE MOLECULAR NUTRITION OF AMINO ACIDS AND PROTEINS A Volume in the Molecular Nutrition Series Edited by D D OMINIQUE ARDEVET InstitutNationaldelaRechercheAgronomique(INRA),Ceyrat,France AMSTERDAM(cid:129)BOSTON(cid:129)HEIDELBERG(cid:129)LONDON NEWYORK(cid:129)OXFORD(cid:129)PARIS(cid:129)SANDIEGO SANFRANCISCO(cid:129)SINGAPORE(cid:129)SYDNEY(cid:129)TOKYO AcademicPressisanimprintofElsevier AcademicPressisanimprintofElsevier 125LondonWall,LondonEC2Y5AS,UK 525BStreet,Suite1800,SanDiego,CA92101-4495,USA 50HampshireStreet,5thFloor,Cambridge,MA02139,USA TheBoulevard,LangfordLane,Kidlington,OxfordOX51GB,UK Copyrightr2016ElsevierInc.Allrightsreserved. Nopartofthispublicationmaybereproducedortransmittedinanyformorbyanymeans,electronicormechanical, includingphotocopying,recording,oranyinformationstorageandretrievalsystem,withoutpermissioninwritingfrom thepublisher.Detailsonhowtoseekpermission,furtherinformationaboutthePublisher’spermissionspoliciesandour arrangementswithorganizationssuchastheCopyrightClearanceCenterandtheCopyrightLicensingAgency,canbe foundatourwebsite:www.elsevier.com/permissions. ThisbookandtheindividualcontributionscontainedinitareprotectedundercopyrightbythePublisher(otherthanas maybenotedherein). Notices Knowledgeandbestpracticeinthisfieldareconstantlychanging.Asnewresearchandexperiencebroadenour understanding,changesinresearchmethods,professionalpractices,ormedicaltreatmentmaybecomenecessary. Practitionersandresearchersmustalwaysrelyontheirownexperienceandknowledgeinevaluatingandusingany information,methods,compounds,orexperimentsdescribedherein.Inusingsuchinformationormethodstheyshouldbe mindfuloftheirownsafetyandthesafetyofothers,includingpartiesforwhomtheyhaveaprofessionalresponsibility. Tothefullestextentofthelaw,neitherthePublishernortheauthors,contributors,oreditors,assumeanyliabilityforany injuryand/ordamagetopersonsorpropertyasamatterofproductsliability,negligenceorotherwise,orfromanyuseor operationofanymethods,products,instructions,orideascontainedinthematerialherein. BritishLibraryCataloguing-in-PublicationData AcataloguerecordforthisbookisavailablefromtheBritishLibrary. LibraryofCongressCataloging-in-PublicationData AcatalogrecordforthisbookisavailablefromtheLibraryofCongress. ISBN:978-0-12-802167-5 ForInformationonallAcademicPresspublications visitourwebsiteathttp://www.elsevier.com/ Publisher:NikkiLevy AcquisitionEditor:MeganBall EditorialProjectManager:KarenMiller ProductionProjectManager:CarolineJohnson Designer:VictoriaPearson TypesetbyMPSLimited,Chennai,India Contents List of Contributors.......................................ix 4. Cellular and Molecular Mechanisms of Protein Synthesis Among Tissues Preface ........................................................xiii J.W.CARBONE,L.M.MARGOLISANDS.M.PASIAKOS 4.1 Introduction..............................................................................39 I 4.2 CellularandMolecularRegulationofHypertrophy...............42 4.3 Myogenesis:TheDevelopmentandRegeneration GENERAL AND INTRODUCTORY ofMuscle...................................................................................43 ASPECTS 4.4 AppliedImplicationsofProteinSynthesisInVivo................45 4.5 ConclusionsandSummaryofKeyPoints................................45 Disclosures.......................................................................................45 1. Bioactive Peptides Derived From Food Proteins References........................................................................................45 D.RE´MOND,I.SAVARY-AUZELOUXANDR.BOUTROU 1.1 PhysiologicalEffectsofFood-DerivedPeptides.........................3 5. Role of Amino Acid Transporters 1.2 InVivoEvidenceofFood-DerivedPeptideEffects...................6 in Protein Metabolism 1.3 BioactivePeptidesReleasedDuringDigestion.........................6 P.M.TAYLOR 1.4 PeptideBioavailability...............................................................7 1.5 Conclusion..................................................................................8 5.1 AminoAcidTransporters:StructureandMolecular References..........................................................................................8 Function...................................................................................49 5.2 AATransportersandCellularFunction..................................52 5.3 AATransportersinWhole-BodyNutrition............................56 2. Protein Intake Throughout Life and Current 5.4 AATransportersinMammalianEmbryonic Dietary Recommendations DevelopmentandGrowth.......................................................59 F.MARIOTTI 5.5 AATransportersandtheImmuneResponse...........................59 5.6 AAandPeptideTransportersasTherapeuticTargets............60 2.1 Introduction..............................................................................13 Acknowledgment.............................................................................60 2.2 CurrentEstimatesforProteinandAminoAcid References........................................................................................60 RequirementsThroughoutLife................................................14 2.3 TheoreticalandPracticalLimitationsandUncertainties......15 2.4 EvidenceforDefiningRequirementsBasedonMeals II RatherThananAverageDailyIntakeinOlderPeople.........17 2.5 TowardOtherCriteriatoDefineRequirements, CELLULAR ASPECTS OF PROTEIN UsingHealth-RelatedParameters?..........................................18 AND AMINO ACIDS METABOLISM 2.6 CurrentDietaryIntakeofProteinandAminoAcids.............20 2.7 ConclusionandPerspectives....................................................21 IN ANABOLIC AND CATABOLIC References........................................................................................22 SITUATIONS 3. Cellular Mechanisms of Protein Degradation Among Tissues 6. Amino Acids and Exercise: Molecular L.COMBARET,D.TAILLANDIER,C.POLGE,D.BE´CHETANDD.ATTAIX and Cellular Aspects C.McGLORYANDS.M.PHILLIPS 3.1 Introduction..............................................................................27 3.2 ProteolyticSystems...................................................................27 6.1 Introduction............................................................................67 3.3 SkeletalMuscleProteolysis......................................................29 6.2 RegulationoftheSizeofHumanMuscleMass....................67 3.4 ProteolysisinViscera................................................................33 6.3 ExerciseMode........................................................................68 3.5 ConcludingRemarks................................................................34 6.4 ProteinType...........................................................................69 Acknowledgments...........................................................................34 6.5 DoseResponseofMPStoProteinIngestionFollowing References........................................................................................34 ResistanceExercise.................................................................69 v vi CONTENTS 6.6 TimingandDistribution........................................................69 9.7 TheMolecularRegulationofSkeletalMuscleProtein 6.7 TheInfluenceoftheAgingProcess......................................71 SynthesisandMuscleProteinBreakdownbyAmino 6.8 TheRoleoftheEssentialandBranched-Chain AcidandInsulin.....................................................................118 AminoAcids..........................................................................72 9.8 Conclusions............................................................................120 6.9 TheMechanisticTargetofRapamycinComplex1 References......................................................................................121 (mTORC1).............................................................................72 6.10 ResistanceExercise,AminoAcids,andmTORC1..............73 6.11 FutureDirections....................................................................74 10. Protein Metabolism and Requirement 6.12 Conclusion..............................................................................75 in Intensive Care Units and Septic Patients References........................................................................................75 P.J.M.WEIJS 10.1 Introduction..........................................................................125 7. Protein Metabolism in the Elderly: Molecular 10.2 ProteinMetabolismintheCriticallyIllPatient................125 and Cellular Aspects 10.3 ProteinRequirementofCriticallyIllPatients: E.L.DILLON MechanisticStudies.............................................................126 10.4 ProteinRequirementsofCriticallyIllPatients: 7.1 AgingandSarcopenia.............................................................79 Outcome-BasedStudies.......................................................127 7.2 ProteinMetabolismintheAgingBody..................................79 10.5 ApplicationinClinicalPractice.........................................129 7.3 Age-RelatedChangesinNutrientSensitivity........................82 10.6 Protein(cid:1)EnergyRatio..........................................................129 7.4 RegulationofmTORSignalinginAging...............................84 10.7 Conclusion............................................................................130 7.5 TheRoleofPhysicalActivityDuringAging..........................86 References......................................................................................131 7.6 AgingandChangesinEndocrineFunction............................87 7.7 MolecularDysregulationofProteinMetabolism DuringAging............................................................................87 11. Muscle Protein Kinetics in Cancer Cachexia References........................................................................................89 J.M.ARGILE´S,S.BUSQUETSANDF.J.LO´PEZ-SORIANO 8. Specificity of Amino Acids and Protein 11.1 Introduction:MuscleWastingastheMainFeature ofCancerCachexia..............................................................133 Metabolism in Obesity 11.2 ControlofSkeletalMassinHealthyConditions...............133 C.GUILLET,C.DOMINGUES-FARIA,S.WALRANDANDY.BOIRIE 11.3 AnabolicSignals..................................................................134 11.4 InflammationandMuscleProteinDegradation..................136 8.1 Introduction:Fat-FreeMassinObesity...................................99 11.5 Cross-TalkBetweenAnabolicandCatabolic 8.2 InsulinResistanceandProteinMetabolism..........................100 Mediators..............................................................................138 8.3 LipotoxicityandMuscleProteinMetabolism.......................101 11.6 TherapeuticApproachestoInfluenceProteinKinetics.....139 8.4 RoleofAdiposeandMuscularCytokinesinthe 11.7 ConclusionsandFutureDirections.....................................141 Cross-TalkBetweenMuscleandAdiposeTissue..................102 References......................................................................................141 8.5 SarcopenicObesityandMetabolicImpairments..................103 8.6 BCAALevelsandMetabolisminObesity............................104 8.7 Conclusion..............................................................................105 12. Amino Acid and Protein Metabolism in References......................................................................................105 Pulmonary Diseases and Nutritional Abnormalities: A Special Focus on Chronic Obstructive 9. Feeding Modulation of Amino Acid Utilization: Pulmonary Disease Role of Insulin and Amino Acids in Skeletal Muscle E.BARREIROANDJ.GEA P.J.ATHERTON,D.J.WILKINSONANDK.SMITH 12.1 Introduction..........................................................................145 9.1 OverviewoftheMetabolicRoleofSkeletalMuscle 12.2 EpidemiologyandDefinitionofNutritional andasanAminoAcidRepository........................................109 AbnormalitiesinChronicRespiratoryPatients..................146 9.2 ImpactofSplanchnicExtractionandSourceofDietary 12.3 DiagnosisofNutritionalAbnormalitiesinPatients...........146 AminoAcidonBioavailabilityandMuscleProtein 12.4 EtiologicFactorsandBiologicalMechanismsInvolved Synthesis.................................................................................111 intheNutritionalAbnormalitiesofPatientsWith 9.3 InfluenceofAminoAcid,MacronutrientComposition, ChronicRespiratoryConditions:COPDasthe andCaloricLoadonMuscleProteinSynthesis....................114 Paradigm...............................................................................147 9.4 EffectsofDoseandDeliveryProfileofAminoAcid 12.5 ProteinMetabolism,Muscles,andExercise ontheFeeding-InducedStimulationofMuscle inHumans............................................................................150 ProteinSynthesis....................................................................115 12.6 PotentialTherapeuticTargetsofNutritional 9.5 InfluenceofMicrovascularResponsestoFeeding AbnormalitiesinChronicRespiratoryPatients..................152 inRelationtoMuscleProteinSynthesis...............................116 12.7 OtherChronicRespiratoryConditions...............................155 9.6 TheRoleofInsulininRegulatingMuscleProtein 12.8 ConclusionsandFuturePerspectives..................................155 Turnover..................................................................................117 References......................................................................................156 vii CONTENTS 13. Amino Acids, Protein, and the 16.3 DetectionofProteinandAminoAcidsDuring Gastrointestinal Tract DigestionandControlofFoodIntakebyFeedback Signaling...............................................................................224 M.J.BRUINS,K.V.K.KOELFATANDP.B.SOETERS 16.4 Protein-InducedReductioninEatingandCentral NeuronalPathways...............................................................226 13.1 Introduction........................................................................161 16.5 Conclusion............................................................................228 13.2 GastrointestinalAminoAcidandProteinMetabolism Acknowledgments.........................................................................228 inHealth.............................................................................161 References......................................................................................228 13.3 TheFirst-PassEffectofaBolusMeal................................163 13.4 GastrointestinalAminoAcidandProteinMetabolism inStressConditions...........................................................165 17. Dietary Protein and Hepatic Glucose Production 13.5 TheProductionofaSubstrateMixtoSupportHost ResponseinStress..............................................................167 C.GAUDICHON,D.AZZOUT-MARNICHEANDD.TOME´ 13.6 ProteinMetabolisminStressStarvation...........................169 17.1 Introduction..........................................................................233 13.7 SubstrateMetabolisminStressStarvationtoSpare 17.2 AminoAcidsasGlucosePrecursorsandEffect Protein................................................................................169 ofProteinIntake..................................................................233 13.8 TheRoleofIndividualAminoAcidsinthe 17.3 InsulinandGlucagonMediatedEffectsofAminoAcids GastrointestinalTract.........................................................170 andProteinsonGlucoseProduction...................................234 13.9 TheRoleoftheIntestineinBileSaltandAmino 17.4 ProteinMealandHepaticGlucoseProduction..................236 AcidMetabolism................................................................172 17.5 HighProteinDietandHepaticGlucoseProduction..........237 13.10 RoleoftheIntestineinAminoAcidMetabolism 17.6 Conclusion............................................................................238 inLiverFailure...................................................................174 References......................................................................................238 References......................................................................................175 18. Impact of Dietary Proteins on Energy Balance, 14. Regulation of Macroautophagy by Nutrients Insulin Sensitivity and Glucose Homeostasis: From and Metabolites Proteins to Peptides to Amino Acids S.LORIN,S.PATTINGRE,A.J.MEIJERANDP.CODOGNO G.CHEVRIER,P.MITCHELL,M.-S.BEAUDOINANDA.MARETTE 14.1 Introduction..........................................................................181 18.1 Introduction..........................................................................241 14.2 OverviewoftheAutophagicPathway................................183 18.2 Conclusion............................................................................256 14.3 TheNutrientCodeofAutophagy.......................................184 References......................................................................................257 14.4 MetabolitesandAutophagy.................................................194 14.5 Conclusion............................................................................196 Acknowledgments.........................................................................197 19. Sulfur Amino Acids Metabolism From Protein References......................................................................................197 Synthesis to Glutathione G.COURTNEY-MARTINANDP.B.PENCHARZ III 19.1 Introduction..........................................................................265 CELLULAR AND MOLECULAR 19.2 FunctionsoftheSAAs........................................................267 ACTIONS OF AMINO ACIDS IN 19.3 PhysiologicalAspectsofSAAMetabolism.........................267 19.4 NutritionalAspectsofSAAMetabolism............................269 NON PROTEIN METABOLISM 19.5 SAARequirement...............................................................272 19.6 Glutathione..........................................................................278 19.7 Conclusions..........................................................................282 15. Dietary Protein and Colonic Microbiota: References......................................................................................282 Molecular Aspects G.BOUDRY,I.LEHUE¨ROU-LURONANDC.MICHEL IV 15.1 Introduction..........................................................................207 DIETARYAMINO ACID AND PROTEIN 15.2 Conclusion............................................................................215 References......................................................................................216 ON GENE EXPRESSION 16. Control of Food Intake by Dietary Amino Acids 20. Adaptation to Amino Acid Availability: Role of and Proteins: Molecular and Cellular Aspects GCN2 in the Regulation of Physiological Functions G.FROMENTIN,N.DARCEL,C.CHAUMONTET,P.EVEN,D.TOME´AND and in Pathological Disorders C.GAUDICHON J.AVEROUS,C.JOUSSE,A.-C.MAURIN,A.BRUHATANDP.FAFOURNOUX 16.1 Introduction..........................................................................221 16.2 TheEffectofProteinIntakeandOverallEnergyIntake 20.1 Introduction..........................................................................289 onBodyWeightandBodyComposition............................222 20.2 TheGCN2-EIF2αPathway.................................................290 viii CONTENTS 20.3 ControlofPhysiologicalFunctionsbyGCN2....................295 22.2 MolecularPathwaysInvolvedinSkeletalMuscle 20.4 InvolvementofGCN2inPathology...................................298 Remodeling...........................................................................319 20.5 Conclusion............................................................................299 22.3 EffectsofFeedingonSkeletalMuscleRemodeling............323 References......................................................................................299 References......................................................................................326 21. Amino Acid-Related Diseases 23. Brain Amino Acid Sensing: The Use of a I.KNERR Rodent Model of Protein-Malnutrition, Lysine Deficiency 21.1 Introduction..........................................................................305 21.2 DisorderofPhenylalanineandTyrosineMetabolism K.TORIIANDT.TSURUGIZAWA (Phenylketonuria,Hyperphenylalaninemia,Tyrosinemia Type1)..................................................................................307 23.1 Introduction..........................................................................331 21.3 UreaCycleDisorders/Hyperammonemias...........................308 23.2 BrainEssentialAASensing:TheCaseoftheRodent 21.4 DisordersofBranched-ChainAminoAcidMetabolism ModelofLysineDeficiency.................................................332 (MapleSyrupUrineDisease,IsovalericAcidemia, 23.3 BrainFunctionalChangesElicitedbyIntragastric PropionicAcidemia,MethylmalonicAcidemia)................310 StimulationbyNutrients,Glucose,Glutamate,and 21.5 ClassicalHomocystinuria(HCU).......................................312 SodiumChloride..................................................................335 21.6 Miscellaneous.......................................................................313 23.4 GlutamateSignalingintheGutTriggers References......................................................................................313 Diet-InducedThermogenesisandAidsinthe PreventionofObesity..........................................................337 23.5 Conclusion............................................................................339 22. Genes in Skeletal Muscle Remodeling and Impact Acknowledgments.........................................................................339 of Feeding: Molecular and Cellular Aspects References......................................................................................339 Y.-W.CHEN,M.D.BARBERIOANDM.J.HUBAL 22.1 CellularEventsInvolvedinSkeletalMuscle Remodeling...........................................................................315 Index..........................................................341 List of Contributors J.M. Argile´s Cancer Research Group, Departament de A. Bruhat Unite´ de Nutrition Humaine, UMR 1019, INRA, Bioqu´ımica i Biologia Molecular, Facultat de Biologia, Universite´ d’Auvergne, Centre INRA de Clermont- Universitat de Barcelona, Barcelona, Spain; Institut de Ferrand-Theix,SaintGene`sChampanelle,France Biomedicina de la Universitat de Barcelona, Barcelona, M.J.Bruins TheHague,TheNetherlands Spain S. Busquets Cancer Research Group, Departament de P.J. Atherton MRC-ARUK Centre for Musculoskeletal Bioqu´ımica i Biologia Molecular, Facultat de Biologia, Ageing Research, School of Medicine, University of Universitat de Barcelona, Barcelona, Spain; Institut de Nottingham,Nottingham,UnitedKingdom Biomedicina de la Universitat de Barcelona, Barcelona, D. Attaix Clermont Universite´, Universite´ d’Auvergne, Spain Unite´ de Nutrition Humaine, Clermont-Ferrand, France; J.W. Carbone School of Health Sciences, Eastern Michigan INRA, UMR 1019, UNH, CRNH Auvergne, Saint Gene`s University,Ypsilanti,MI,UnitedStates Champanelle,France C. Chaumontet UMR Physiologie de la Nutrition et du J. Averous Unite´ de Nutrition Humaine, UMR 1019, INRA, Comportement Alimentaire, AgroParisTech, INRA, Universite´ d’Auvergne, Centre INRA de Clermont- Universite´ Paris-Saclay,Paris,France Ferrand-Theix,SaintGene`sChampanelle,France Y.-W. Chen Department of Integrative Systems Biology, D. Azzout-Marniche UMR Physiologie de la Nutrition et George Washington University, Washington DC, USA; du Comportement Alimentaire, AgroParisTech, INRA, Center for Genetic Medicine Research, Children’s Universite´ ParisSaclay,Paris,France NationalHealthySystem,WashingtonDC,USA M.D. Barberio Center for Genetic Medicine Research, G. Chevrier Department of Medicine, Faculty of Medicine, Children’sNationalHealthySystem,WashingtonDC,USA Cardiology Axis of the Que´bec Heart and Lung Institute, E. Barreiro Pulmonology Department, Muscle and Lung Que´bec, QC, Canada; Institute of Nutrition and Cancer Research Group, IMIM-Hospital del Mar, Parc de FunctionalFoods,LavalUniversity,Que´bec,QC,Canada Salut Mar, Health and Experimental Sciences Department P. Codogno INEM, Institut Necker Enfants-Malades, Paris, (CEXS), Universitat Pompeu Fabra (UPF), Barcelona France; INSERM U1151-CNRS UMR 8253, Paris, France; Biomedical Research Park (PRBB), Barcelona, Spain; Universite´ ParisDescartes,Paris,France Centro de Investigacio´n en Red de Enfermedades L. Combaret Clermont Universite´, Universite´ d’Auvergne, Respiratorias (CIBERES), Instituto de Salud Carlos III Unite´ de Nutrition Humaine, Clermont-Ferrand, France; (ISCIII),Barcelona,Spain INRA, UMR 1019, UNH, CRNH Auvergne, Saint Gene`s M.-S. Beaudoin Department of Medicine, Faculty of Champanelle,France Medicine, CardiologyAxisoftheQue´becHeartandLung G. Courtney-Martin Faculty of Kinesiology & Physical Institute, Que´bec, QC, Canada; Institute of Nutrition and Education, Department of Clinical Dietetics, University of FunctionalFoods,LavalUniversity,Que´bec,QC,Canada Toronto, The Hospital for Sick Children, Toronto, ON, D. Be´chet Clermont Universite´, Universite´ d’Auvergne, Canada Unite´ de Nutrition Humaine, Clermont-Ferrand, France; N. Darcel UMR Physiologie de la Nutrition et du INRA, UMR 1019, UNH, CRNH Auvergne, Saint Gene`s Comportement Alimentaire, AgroParisTech, INRA, Champanelle,France Universite´ Paris-Saclay,Paris,France Y. Boirie Clermont Universite´, Universite´ d’Auvergne, E.L. Dillon Department of Internal Medicine, Division of Unite´ de Nutrition Humaine, Clermont-Ferrand, France; Endocrinology and Metabolism, The University of Texas INRA, UMR 1019, UNH, CRNH Auvergne, Clermont- MedicalBranch,Galveston,TX,UnitedStates Ferrand, France; CHU Clermont-Ferrand, service de NutritionClinique,Clermont-Ferrand,France C. Domingues-Faria Clermont Universite´, Universite´ d’Auvergne, Unite´ de Nutrition Humaine, Clermont- G.Boudry INRAUR1341ADNC,St-Gilles,France Ferrand, France; INRA, UMR 1019, UNH, CRNH R. Boutrou INRA, UMR 1253, Science et Technologie du Auvergne,Clermont-Ferrand,France laitetdel’œuf,Rennes,France ix

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