蛋白质和氨基酸代谢（英文版）

ProteinandAminoAcidMetabolismCatabolismofaminoacidAnabolismofaminoacid

Thecontents:1.Dietaryproteinnutrition2.Digestion,Absorptionandputrefaction(腐败)3.Generalpathwaysofaminoacidcatabolism4.Ammoniametabolism5.MetabolismofindividualaminoacidsLearningoutcomes*

Bytheendofthislecture,youshouldlearn:

DemonstrateanunderstandingofthemajorpathwaysofaminoacidsmetabolismExplainthetransaminationanddeaminationreactionsingeneralpathwayofaminoacidscatabolism.Discusstheureacycle，graspthephysiologicalsignificanceandthekeyenzymes.Section1

DietaryProteinNutrition

1.Keepthecellsandtissuesgrowing,renewingandmending(structuralfunction)2.Takepartinsomekindsofimportantphysiologicalactivities(dynamicfunction)3.Oxidationandsupplyenergy§1.1Thesignificanceofproteins

2023/10/107soybeanProteindeficiency——kwashiorkorEmaciationGeneralizededema(全身性水肿)Hepatomegaly(肝肿大)Abdomenbulged（腹部膨隆）

§1.2Therequirementsandnutritiousvalueofproteins1.NitrogenbalanceMeasuringtheamountofintakeandlossesoftotalnitrogen,canhelpustoknowthegeneralsituationofproteinmetabolism.threekindsofconditions:Normalnitrogenbalance（nitrogenequilibrium）

intakeN=lossesN2)PositivenitrogenbalanceintakeN>lossesN3)NegativenitrogenbalanceintakeN<lossesN2.PhysicalrequirementsofproteinsLowestrequirement:30~50g/dayRecommendrequirement:80g/day(65kgman)3.Nutritionvalueofproteins(1)Essentialaminoacids:Aminoacidsthatcannotbesynthesizedbythebodyandmustbeobtainedfromthediet.8kindsofessentialAAs:

Val,Ile,Leu,Phe,Met,Trp,Thr,Lys缬异亮亮苯丙蛋色苏赖携一两本淡色书来(2)Non-essentialaminoacidsother12kindsofAAs(3)Semi-essentialaminoacids

Tyr←Phe

Cys←MetNote:HisandArgareessentialAAsforinfantsandchildren.(4)ComplementaryeffectofdietaryproteinsTwoormoreplantproteinsareconsumedtogetherwhichcomplementeachotherinessentialaminoacidcontent.legumescerealsSection2

Digestion,AbsorptionandPutrefaction§2.1Digestionsite:stomach,smallintestineenzymes:pepsin

pepsinogenPeptidebondsofaromaticAApeptone

Proteolyticenzymesofpancreatic

juiceendopeptidasesexopeptidasestrypsin:Arg,Lys(C)chymotrypsin:Tyr,Trp,Phe,Met,Leu(C)elastase:Ala,Gly,Ser(C)carboxypeptidaseaminopeptidase内肽酶外肽酶trypsinchymotrypsinogenelastaseprocarboxypeptidasetrypsinogenenterokinase(肠激酶)chymotrypsinproelastasecarboxypeptidase19TheactivationprocessoftrypsinogenAcutepancreatitisPancreasdigestitselfPancreasnecrosis§2.2AbsorptionTheabsorptionofAAisanactivetransportprocessSite:smallintestinalmucosacellsForm:AA,oligopeptide,dipeptideMechanism:activeabsorptionprocessneedsATP

extracellularmembraneintracellularAAAANa+Na+Na+ADP+PiATPAA-Na+transportNa+-K+

ATPaseSecondaryactivetransportTheprocessofsecondaryactivetransport2.γ-glutamylcycle（Meistercycle）γ-谷氨酰基循环

TransportAAviaglutathione(GSH)GSHregeneration谷氨酸

5-氧脯氨酸酶ATPADP+Pi半胱氨酰甘氨酸(Cys-Gly)半胱氨酸甘氨酸二肽酶γ-谷氨酰环化转移酶氨基酸5-氧脯氨酸γ-谷氨酰半胱氨酸γ-谷氨酰半胱氨酸合成酶ADP+PiATP谷胱甘肽合成酶ATPADP+Pi

γ-谷氨酰基转移酶谷胱甘肽

GSHγ-谷氨酰氨基酸AA§2.3

PutrefactionofproteinsConcept:Someundigestedproteinsandnoabsorbedproductsareanaerobicdecomposedbythebacteriaincolon.Theproductsaretoxictobodyexceptfewvitaminandfattyacid.1)Productionofamines2)Productionofammonia(NH3)Twosources:(1)Metabolismonunabsorbedaminoacids(2)Ureahydrolyzedbyurease3)SomeothertoxicmaterialsTyr→phenolTrp→indoleCys→hydrogensulfide(H2S)FiberrichfoodsSection3GeneralMetabolismofAminoAcidOverviewofthecatabolismofaminoacidsinmammals§3.1ThesourcesandfatesofAAsAminoacidmetabolicpool:aminoacidsinintracellularandextracellularfluids.1.SourcesofaminoacidsDietaryproteinfromintestineBreakdownoftissueproteinSynthesisinthebody

2.FatesofaminoacidsSynthesisofproteinsDeamination

DecarboxylationSynthesisofnon-proteinnitrogencompoundssuchaspurineandpyrimidinegeneralmetabolismofAAsProteinturnover:degradationandresynthesisofprotein§3.2DegradationofproteinincellsBodyproteinAminoAcids1-2%proteinsdegradation75-80%AAsreutilizationfornewproteinsynthesishalftime（t1/2）DegradationofcellularproteinsTherearetwomajorintracellulardevicesinwhichdamagedorunneededproteinsarebrokendown.lysosomes

proteasomes

1.LysosomalpathwayExogenousproteins,membrane-associatedproteinsandlong-livedproteinsATP-independentprocessCathepsins2.Proteasomal(Cytosol)pathwayAbnormalproteins,damagedproteinsandshort-livedproteinsATPandubiquitinProteasome§3.3ThecatabolismofAAs1.DeaminationofAAs3types:

transaminationoxidativedeamination

uniondeamination(transdeamination)(1)transaminationaminotransferase

(氨基转移酶)transaminase

(转氨酶)

Transaminationistheprocessbywhichanaminogroup,usuallyfromglutamate,istransferredtoanα-ketoacid,withformationofthecorrespondingaminoacidplusα-ketoglutarate.

Keypoints:①reversible②Lys,Thr,Procan’tbetransaminated.Aminotransferasesutilizeacoenzyme-pyridoxalphosphate-whichisderivedfromvitaminB6.Nonetdeamination(lossofaminogroup)ALT:Alanineaminotransferase(inliver)

AST:Aspartateaminotransferase(inheart)Twoimportanttransaminases:theactivitiesofALT,ASTineachorgansofhealthyhumantissue

ALTASTtissue

ALTAST

liver

44000142000pancreas

200028000

kidney

1900091000spleen

120014000heart

7100156000lung

70010000muscle

480099000serum

1620Site:liver,

brain,kideny

coenzyme:NAD+orNADP+Inhibitor:GTP,ATPActivator:

GDP,ADPL-GluNH3α-ketoglutarateNAD(P)+NAD(P)H+H+H2O(2)Oxidativedeamination

L-glutamatedehydrogenaseL-glutamateα-ketoglutarate＋NH3

L-glutamatedehydrogenase

NAD+NADH+H+(NADP+)(NADPH+H+)(3)Transdeamination

（Uniondeamination）Theα-aminogroupofmostaminoacidsistransferredtoα-ketoglutaratetoformanα-ketoacidandglutamatebytransaminase.Glutamateisthenoxidativelydeaminatedtoyieldammoniaandα-ketoglutaratebyglutamatedehydrogenase.GluL-glutamatedehydrogenaseα-ketoglutaratetransaminaseNH4+α-AANAD++H2Oα-ketoacidNH32HHighactivitywidespreadMaindeaminationwayNADH+H+CenteronL-glutamatedehydrogenasemalate

腺苷酸代琥珀酸

(IMP)腺苷酸代琥珀酸合成酶α-ketoglutarateAAGluα-ketoacid

转氨酶1oxaloacetateAspAST腺苷酸脱氨酶H2ONH3fumarate(AMP)(4)

Purinenucleotidecycle(inmuscle)

2.Metabolismof-ketoacid(1)Formationofnon-essentialAAs(2)Formationofglucoseorlipids(3)Provideenergy

catabolitesofaminoacid-KetoglutarateSuccinylCoAFumarateOxaloacetatePyruvateAcetylCoAAcetoacetylCoAIntermediatesofTACPEPGlucoseFattyacidKetonebodies

Aminoacidsofconvertedintoketonebodiesorfattyacidsaretermedketogenicaminoacids.Aminoacidsofconvertedintoglucosearetermedglucogenicaminoacids.Aminoacidsofconvertedintobothglucoseandketonebodiesaretermedglucogenicandketogenicaminoacids.ClassificationtypesaminoacidsGlucogenicAAsothersGlucogenicandketogenicAAsIle,Phe,Tyr,Trp,ThrKetogenicAAsLeu,LysSection4

MetabolismofAmmonia1.Sources:⑴Endogenoussources:

①

DeaminationofAAs--mainsource②Catabolismofothernitrogencontainingcompounds③Kidneysecretion(Gln)§4.1Sourceandoutletofammonia(NH3)

⑵Exogenoussources：①Putrefactionintheintestine.②Degradationofureaintheintestine2.Outlets:(1)Formationofurea(2)FormationofGln(3)Excreteinurine(4)SynthesisofAA§4.2TransportationofNH31.Alanine-glucosecycle2.TransportationofammoniabyGln

1.Alanine-glucosecycle2.TransportationofammoniabyGln§4.3Formationofurea1.Site:liver(mitochondriaandcytosol)2.Process---------ornithinecycle（ureacycle）

①Formationofcarbamoylphosphate(inmitochondria)

CarbamoylphosphatesynthetaseⅠ(CPSⅠ)isanallostericenzymeandisabsolutelydependentuponN-acetylglutamicacid(AGA)foritsactivity.②Formationofcitrulline

(inmitochondria)OCT:ornithinecarbamoyltransferase③Formationofarginine(incytosol)twosub-stepsASS:argininosuccinatesynthetaseASL:argininosuccinatelyase④Formationofurea(incytosol)Totalformula：Linksbetweentheureacycleandcitricacidcycle3.SummaryofureasynthesisOnenitrogenofureamoleculecomesfromammonia,anothernitrogencomesfromAsp.Synthesisofaureawillconsume4~P.Keyenzyme:ASS；CPS-IConverttheammoniaintourea

Normalcondition：NH3<1mg/L(0.6umol/L)

centralnervoussystemdysfunctionsymptoms：tremor（震颤）slurredspeech（语言障碍）blurredvision（视力模糊）

coma（昏迷）deathAmmoniamustbedisposedquickly4.hyperammonemiaTAC↓LackofenergyCNSdysfunctionα-ketoglutarateGluGlnNH3NH3

（brain）α-ketoglutarate↓MolecularbasisSection5MetabolismofindividualAminoAcidDecarboxylationofaminoacidsMetabolismofonecarbonunitMetabolismofsulfur-containingAAsMetabolismofaromaticAAsMetabolismofbranched-chainAAs

§5.1Decarboxylationofaminoacids1.Glu→γ-aminobutyricacid

(GABA)2.Cys→taurine3.His→histamine

4.Trp→5-hydroxytryptamine(5-HT)(serotonin)

5.Polyamines§5.2Metabolismofonecarbonunit1.OnecarbonunitOnecarbonunits(orgroups)areone

carbon-containinggroupsproducedincatabolismofsomeaminoacids.

2.Tetrahydrofolicacid(FH4)OnecarbonunitsarecarriedbyFH4.TheN5andN10ofFH4participateinthetransferofonecarbonunits.

3.Formationofonecarbonunit(1)Ser→N5,N10-CH2-FH4

(2)Gly→N5,N10-CH2-FH4(3)His→N5-CH=NHFH4(4)Trp→N10-CHOFH44.Onecarbonunitexchange5.SignificanceofonecarbonunitSubstanceforsynthesisofnucleicacid.N10－CHOFH4N5,N10－CH2－FH4§5.3Metabolismofsulfur-containingAAs

Methionine,cysteineandcystine1.Metabolismof