代谢与能量英文教学课件：Physiological functions and nutrition issues of proteins

Decomposition

ofproteins

&

MetabolismofaminoacidsChapter1

PhysiologicalfunctionsandnutritionissuesofproteinsFunctionsofproteinsandaminoacidsCellgrowth,repair,andmaintenancephysiologicallyactivesubstancesHormone、NeurotransmitterSpecialphysiologicalfunctionsenzyme、antibody、Bloodcoagulation、HbEnergysourceNitrogenbalanceThedifferencebetweenintakeandoutputofnitrogenouscompoundsisknownasnitrogenbalance.Itcanevaluatethestateofproteinnutrition.

intakeN:fromthedietLossesN:lossesinurine,feces,sweat,shedskinNitrogenbalance:equilibrium

Inahealthyadult,nitrogenbalanceisequilibrium,whenintakenitrogenequalsoutputnitrogen,andthereisnochangeinthetotalbodycontentofprotein.

Positivenitrogenbalance

Inchildren,pregnantwomen,orpeopleinrecoveryfromproteinloss,theexcretionofnitrogenouscompoundsislessthanthedietaryintakeandthereisnetretentionofnitrogeninthebody.NegativenitrogenbalanceInresponsetotraumaorinfection,oriftheintakeofproteinisinadequatetomeetrequirements,theexcretionofnitrogenouscompoundsismorethanthedietaryintakeandthereisnetlossofproteinnitrogenfromthebody.NutritionalRequirementsforproteinsDailyproteinintakeadult1-1.2g/kgChild/pregnantwoman2-4g/kgNitrogenisalsoconstantlybeinglostfromthebodyeveryday.Essential

/

conditionallyessential

/nonessentialaminoacidsEssentialaminoacids:

theaminoacidswhichcan’tbesynthesizedinthebodyandmustbeobtainedfromfood.

Valine/Val,Leucine/Leu,Isoleucine/Ile,

Threonine/Thr,Phenylalanine/Phe,

Tryptophan/Trp,Lysine/Lys,Methionine/MetNonessentialaminoacids:

theaminoacidsthathumancansynthesizeandarenotneededinthediet.Glycine/Gly,Alanine/Ala,Proline/Pro,Serine/Ser,

Tyrosine/Tyr,Asparagine/Asn,Glutamine/Gln,

Cysteine/Cys,Glutamate/Glu,Aspartate/AspConditionallyessentialaminoacids:

theaminoacidsthataresynthesizedatratesinadequatetosupportgrowthofchildren.

Histidine/His,Arginine/ArgBiologicalValue(BV)ofProteinsMeasureofProteinQualitybasedonNITROGENRETENTIONBV=X100theessentialaminoacidscomposition.NitrogenabsorptionNitrogenretentionComplementaryeffectof

dietaryproteinsProteinsorigin

lysinetryptophangraindeficientrichsoybeanrichdeficienttogetherrichrichChapter2

Digestion,AbsorptionandPutrefactionofproteinsDigestionDietaryproteins

StomachsmallintestineproteasesFreeaminoacids

SmallpeptidesProteasesendopeptidasescleavetheinternalpeptidebonds

pepsintrypsinchymotrypsinelastaseexopeptidasesremoveAAsfromN-orC-terminalendscarboxypeptidaseAcarboxypeptidaseBAminopeptidase

Aminoacids+FreeaminoacidsDipeptidaseCarboxypeptidaseAminopeptidaseendopeptidasesAbsorptionIntestineFreeaminoacidsMechanisms:sodiumpump，anATP-requiringprocessγ-glutamylcycleγ-glutamylcycleAminoacidcysteineglycine(Cys-Gly)GSH1γ-glutamyl-aminoacid

γ-glutamyl-transpeptidaseAminoacid5-OxiprolineGlutamate

ATPADP+Piγ-glutamylcysteineADP+PiATPATPADP+Pi

CellmembranePutrefactionInthelargeintestine,thedecompositionoftheundigestedproteinsandunabsorbedaminoacidsbybacteriaiscalledputrefaction.Decarboxylation:aminesReductivedeamination:

NH3,phenol,indole,CH4Fecalexcretion,ProcessedinliverNH3intheintestinePutrefactionDegradationofureaintheintestineH2N-CO-NH2

urease

2NH3+CO2ImportantsourceofbloodNH3Chapter3

GeneralMetabolism

ofAminoAcids

Proteinturnoverthedegradationandsynthesisofprotein.

1%-2%oftotalbodyproteinsturnovereachday.Halftime(t1/2):thetimerequiredtoreducetheproteinsconcentrationto50%ofitsinitialvalue.TwopathwaystodegradeproteinsincellsLysosomalpathwayextracellular;membrane-associated;long-livedproteinsATPindependentprocessdegradedbycathepsin(pH5.0)Cytosolpathwayabnormal,damaged,short-livedproteinsrequireATPandubiquitin

degradedbyproteosome(pH7.8)

Aminoacidsmetabolicpool-

ketoaciddeamination

KetobodyEnergyglucoseAminedecaboxylationNH3

ureaconversionNon-proteinNitrogencompoundsDietaryproteinsabsorptionAminoacisSynthesis(non-essencialAAs)AminoacidmetabolicpoolTissueproteinssynthesisdegradationTissueproteinsSource

utilizationDeaminationofAAsRemovaloftheaminogroupsofAAsOxidativedeamination

Transamination

CombineddeaminationPurinenucleotidecycle

Non-oxidativedeamination

OxidativedeaminationofL-glutamateL-glutamateiscatalyzedbyL-Gludehydrogenasetoreleaseammoniaandtobetransformedtoα-ketoglutarate.L-glutamateDehydrogenase

NAD+,NADP+widedistribution,highactivity(exceptmuscle)ReversibleAllostericenzymeinhibitors:GTP,ATP;activators:GDP,ADPTransaminationTransaminationinterconvertspairsofα-aminoacidsandα-ketoacids.Theα-aminogroupofanaminoacidistransferredtoα-ketoacid,thentheα-aminoacidformsacorrespondingα-ketoacid,theα-ketoacidformsacorrespondingα-aminoacid.Alltheproteinaminoacidsexceptlysine,threonine,prolineandhydroxyprolineparticipateintransamination.CatalyzedbytransaminaseTransaminasewidedistribution!REVERSIBLE!-NH2,notreallyremovedcoenzyme:pyridoxalphosphate(vit.B6derivative)The-aminogroupofmostaminoacidsistransferredto-ketoglutaratetoformglutamatealanineaminotransferase

(ALT=GPT)aspartateaminotransferase

(AST=GOT)Aminotransferasesimportantinmedicine(„transaminases“)liverheartCofactoroftransaminase:

pyridoxalphosphate

AminoacidpyridoxalphosphateSchiffbaseIsomerofSchiffbasepyridoxaminephosphateα-ketoacidpyridoxalphosphatepyridoxaminephosphateSchiffbaseIsomerofSchiffbaseIsomerofSchiffbaseSchiffbaseIsomerofSchiffbaseCombineddeamination/transdeaminationThecombinedactionofanaminotransferaseandglutamatedehydrogenaseisreferredtoastransdeamination.The-aminogroupofmostaminoacidsistransferredto-ketoglutaratetoformglutamatebytransaminase.Thenglutamateisdeaminated

toammoniaand-ketoglutaratebyglutamatedehydrogenase.

PurineNucleotideCycleTheactivityofL-glutamatedehydrogenaseislowintheskeletalmuscleNon-oxidativedeaminationMetabolismofAmmoniaAlaUreaUrea(intestine)Putrefactionnon-essencialAAsN-compoundNH3IntestinalabsorptionNH3undigestedproteinsnoabsorbedAAsUreaseTissuesdeaminationGlnAAsMuscleLiverLiver,kidneyGlutaminaseGlnsynthetaseMuscle,etalSources

OutletsDeaminationofAAs--mainsourceOxidativedeaminationTransdeaminationSourcesofammonia:HydrolysisofGln(Kidneysecretion）Intestinalabsorption

PutrefactionDegradationofureaintheintestineH2N-CO-NH2

urease

2NH3+CO2Sourcesofammonia:TransportationofNH3Onlytracesofammonia(NH3)existinblood.NH3istoxictothecentralnervoussystem.Soitmustbetransportedinnontoxictype.glutamineAlanineglutaminesynthetaseBrain,muscleGLUTAMINE=themostimportanttransportformafaminonitrogeninblood„amidation“

ofglutamate=sidechaincarboxylicgroupofGluisconvertedtoamidegroupGlutaminase

catalyzeglutamine→glutamate+NH4+

liver:NH3

→Urea

kidneysecretionGLUTAMINEThetemporarynon-toxicstorageandtransportformofNH3AkindofdetoxificationpathwayServesasasourceofaminogroupsinavarietyofbiosyntheticreactions

Nitrogencompounds:

purines,pyrimidines……Maintaintheacid-basebalanceSynthesizedinbrainandmuscle

DegradedinkidneyandliverAlanineservesasacarrierofammoniaandofthecarbonskeletonofpyruvatefromskeletalmuscletoliver.Theammoniaisexcretedandthepyruvateisusedtopro-duceglucose,whichisreturnedtothemuscle.Glucose-AlaninecycleGlucose-AlaninecycleproteinAminoacidNH3Gluα-keto-glutarate

pyruvateMuscleBloodAlaglucoseα-ketoglutarateGlupyruvateNH3ureaLiverglucoseglucoseAlaAlaFormationofUreaThemajorproductofammonia.Synthesizedinliver,excretedbykidney.Theprocessiscalledureacycleorornithine

cyclefoundbyHansKrebs.Thesynthesisof1molurearequires:1molammonia1molα-aminonitrogenfromaspartate1molCO24molATP1.ThesynthesisofcarbamoylphosphateinmitochondriaCarbamoylphosphatesynthetaseⅠ(CPS

I)ATPIrreversibleCPSⅠ:allostericenzymeActivator:N-acetylglutamicacid(AGA)

Glu+CH3COSCOAAGAsynthaseAGA+HS-COAAGAsynthase:allostericenzymeActivator:Arg2.Carbamoylphosphateplusornithine

formscitrullineinmitochondriaOrnithinecarbamoyltransferase(OCT)incytosol,twosub-steps*Citrullineplusaspartateformsargininosuccinate3.FormationofArginine

ASAS:argininosuccinatesynthetaseRate-limitingenzymeASAL:argininosuccinatelyase3.FormationofArginine*Cleavageofargininosuccinateformsarginine&fumarateReutilizationofaspartateAminoacidoxaloacetateMalateα-ketoglutarateglutamateα-ketoacidFumarateArginine

Aspartate

argininosuccinatecitrulline4.Cleavageofargininereleasesurea

&re-formsornithineincytosol,ArginaseThesynthesisofcarbamoylphosphateinitiatesureabiosynthesis,carbamoylphosphateplusOrnithineformscitrulline,citrullineplusaspartateformsargininosuccinate,cleavageofargininosuccinateformsarginine&fumarate.Then,Cleavageofargininereleasesurea&re-formsornithine.

Somereactionsoccurinthematrixofthemitochondrion,otherreactionsinthecytosol.

Rate-limitingenzyme:ASASargininosuccinatesynthetase

Urea(ornithine)cycleDetoxificationpathway(NH3istoxicforbrain)ProceedsintheliverAmmonia、aspartateLocalizedinmitochondria/cytoplasm

synthesisofcarbamoylphosphateFormationofcitrullineSynthesisofArginineHydrolysisofargininemitochondriacytosolUrea(ornithine)cycleRate-limitingenzyme:ASASCanacidifyanorganism(consumesHCO3-)Needsenergy

(3ATP,but4energyrichbonds)Connectedwithcitratecyclethroughfumarate

Ureaisendproductof–NH2metabolism

(→urine)RegulationinureabiosynthesisDietarynitrogenintake:CPS-Ⅰ:regulatoryenzymeactivationcarbamoylphosphate

synthetaseI

(=mitochondrial)N-acetylglutamate(AGA)N-acetylglutamate

synthasearginineGlu+CH3COSCOAAGAsynthaseAGA+HS-COARegulationinureabiosynthesisornithine、citrulline、arginineKeyenzyme:

ASASHyperammonemiaHighlevelofammoniaintheblood.Reasons:

-inbornerrorsofenzymesinureacycle-liverfailureDamage:

(ammoniapoisoning)comaandirreversiblebraindamageMechanism

ofthebraindamage:TAC↓-

ketoglutarateGlutamateglutamineNH3NH3Quantityof-

ketoglutarateinbrain↓ATPdeficiencyGlutamate

inbrain↓GABA↓Metabolismof-ketoacid(1)Formationofnon-essentialAAs(2)Formationofglucoseorlipid(3)Energysource

1.Formationofnon-essentialAAs-ketoacidnon-essentialAAs

pyruvate→

Ala

oxaloacetate→Asp

-ketoglutarate→

GluGlu-ketoglutarate

TCAoxaloacetateAsp

2.FormationofglucoseorlipidGlucogenicaminoacids:

Theaminoacidsthataredegradedtopyruvate,-ketoglutarate,succinyl-CoA,fumarate,and/oroxaloacetatecanbeconvertedtoglucoseandglycogen.

KetogenicaminoacidscanbedegradedtoacetylCoAoracetoacetylCoA,whichareprecursorsofproducingketonebodies.LeuKetogenicandglucogenicaminoacids

Ile,Phe,Trp,TyrCategoryAminoacidsGlucogenicAAsAla,Arg,Asp,Cys,Glu,Gly,His,Met,Pro,Ser,Thr,Val,Gln,AsnKetogenicAAsLeuGlucogenic&KetogenicAAsIle,Phe,Trp,Tyr,LysPEPphosphoglycetateglucoseglucoseAlaCysGlySerTrpAcetylCoApyruvateIleLeu

TrpAsnAspPheTyrValThrMetIleLeuLys

TrpPheTyr

GluGlnArgHisProAcetoacetylCoAKetobodyGlycerol3-phosphateFAsLipidsTAGSuccinylCoAFumarateoxaloacetateα-ketoglutarateCitrateCO2CO2TACpyruvate

Gly,Cys,Ala,Ser,Trpoxaloacetate

Asp,Asn-ketoglutarateGlu,Gln,Pro,Arg,Hissuccinyl-CoAVal,Ile,Met,ThrfumaratePhe,Tyracetyl-CoAIle,Leu,Trpacetoacetyl-CoALys,Leu,Phe,Tyr,TrpglucogenicAAsketogenicAAsDecarboxylationofAminoAcidDecarboxylaseCoenzyme:pyridoxalphosphateAmide:PhysiologicaleffectsdecarboxylaseAminoAcidAmineRCH2NH2+CO2Puridoxalphosphate1.γ-aminobutyricacid(GABA)GABAisformedbydecarboxylationofL-glutamate,areactioncatalyzedbyL-glutamatedecarboxylase.

Itfunctionsinbraintissueasaninhibitoryneurotransmitterbyalteringtransmembranepotentialdifference.2.5-hydroxytryptamine(5-HT)Followinghydroxylationoftryptophanto5-hydroxytryptophanbyhydroxylase,subsequentdecarboxylationformsserotonin.Serotoninisoneofinhibitoryneurotransmittersinbrain,andapotentvasoconstrictandstimulatorofsmoothmusclecontraction.3.Taurine

Cysteineisaprecursoroftaurinethatconjugateswithbileacidssuchastaurocholicacid.4.Histamine

Vasodilation:allergicreactionstimulatethesecretionof

pepsinandhydrochloricacidcausecontractionofsmoothmuscle

Bronchialasthma

5.Polyaminesimportanttocellproliferation

andtissuegrowthChapter4

Metabolismof

IndividualAminoAcidsMetabolismofonecarbonunitMetabolismofsulfur-containingAAsMetabolismofaromaticAAsMetabolismofbranched-chainAAsOneCarbonUnitsonecarbon-containinggroupsthatareproducedincatabolismofsomeaminoacidsarecarriedbyFH4

Tetrahydrofolate(FH4)FolicacidFH2FH4NADPH+H+NADP+NADPH+H+NADP+DihydrofolatereductaseFormationofonecarbonunitSer→N5,N10-CH2-FH4Gly→N5,N10-CH2-FH4His→N5-CH=NHFH4Trp→N10-CHOFH4OnecarbonunitexchangeMethylene-FH4Methyl-FH4AsdonorsinpurineandpyrimidinesynthesisThemethylationofmanysubstratesInterconnectionoftheAAsmetabolism

withthenucleicacidsmetabolismFunctionofonecarbonunitsdUMPdTMPMethylene-FH4FH2CystineMethioninesulfur-containingaminoacidsCysteineMetabolismofsulfur-containingaminoacidsMetandtransmethylationEssentialaminoacidImportant–CH3groupdonoractivatedmethionine:

S-adenosylmethionine(SAM)Thefigureisfrom/thcme/mwking/amino-acid-metabolism.html(Jan2007)Formationofactivatedmethionine

=S-adenosylmethionine(SAM)SAMissynthesizedfromATPandmethioninebytheactionofmethionineadenosyltransferase.SAMisusedas–CH3groupdonorinmetabolicmethylations.SAMSAMisthepreferredcofactorforbiologicalmethylgrouptransfers.Tosynthesizemanyimportantmaterialssuchas:choline,creatine,etcModificationofproteinsandnucleicacidBiotransformationB12RegenerationofMet(vitamins:folate+B12)MetcycleSAMissynthesizedfromATPandmethioninebytheactionofmethionineadenosyltransferase.TransferofthemethylgroupfromS-adenosylmethioninetoanacceptoryieldsS-adenosylhomocysteine,whichissubsequentlybrokendowntohomocysteineandadenosine.Methionineisregeneratedbytransferofamethylgrouptohomo-cysteineinareactioncatalyzedbymethioninesynthase,andmethionineisreconvertedtoS-adenosylmethioninetocompleteanactivated-methylcycle.MetcycleRegenerationofMetN5-CH3FH4istheindirectdonorofmethylinthebodyThefreefolicacidorVitB12decreasewillleadtomegaloblastic

anemia.Folicacid/VitB12deficiency

-MegaloblasticanemiaSecondarytothedeficiencyofvitaminB12,thereisfunctionaldeficiencyoffolate.

1.SAMformshomocysteine,whichmayberemethylatedbymethyl-tetrahydrofolatecatalyzedbymethioninesynthase,aVitB12-dependentenzyme.2.Thereductionofmethylene-FH4tomethyl-FH4isirreversible.3.ImpairmentofmethioninesynthaseinB12deficiencyresultsintheaccumulationofmethyltetrahydrofolate–the“folatetrap”.B12Thesynthesisofth