Carbohydrate metabolism.docx
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Carbohydrate metabolism.docx
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Carbohydratemetabolism
substratelevelphosphorylation
底物分子内部能量重新分布,生成高能键,使ADP磷酸化生成ATP的过程,称为底物水平磷酸化.ATPgeneratedbytransferringhighenergyphosphatedirectlytoADPfrommetabolite.
IntroductionofCarbohydrateMetabolism
IntroductionofGlycolysis
KeypathwayhavingthethreeKeyenzymes:
TwoATP-consumedpathways:
TwoATP-producedpathways:
Pathway:
NAD+,NADH+H+
Glycolyticpathway:
(1)happenposition:
Cytosol
(2)totalreaction:
glucose+2Pi+2ADP+2NAD+—————〉2pyruvate+2ATP+2NADH+2H++2H2O
10stepreactions,threeofthemareirreversible
2ATPareconsumedinthefirststage,and4ATPareproducedinthelatterstage.
(3)outletofpyruvate
(4)outletofNADHH+
Regulationofglucagonsandinsulin
Glucagons:
Insulin:
Insulin---(+)-glucokinasegenetranscription
Regulationofglycolysis
Ⅰ.6-phosphofructokinase-1(PFK-1)
⏹Allostericactivators:
ADP,AMP,F-1,6-DP(positivefeedback),F-2,6-DP
⏹Allostericinhibitors:
ATP,citricacid
⏹F-2,6-DPisproducedbyPFK-2,thestrongesteffecterregulation(μmol)ofglycolysis
Ⅱ.Pyruvatekinase(PK)
⏹AllostericInhibitors:
ATP,alanine
⏹Allostericactivators:
F-1,6-DP
Ⅲ.Hexokinase(HK)
⏹G-6-Pnegativefeedback
⏹glucokinase(liver,pancrea),alsocalledhexokinaseD,haslowaffinitytoglucose,notinhibitedbyG-6-PbutF-6-P.
⏹
⏹Insulin-----glucokinasegenetranscription
RegulationofglycolysisByFBP-2/PFK-2
Significanceoftheglycolysis
1.Energyrapidsupplywhenshortageofoxygene.g.strongexercise,musclecontraction.
2.Specialtissue(orcell)supplyenergye.g.nervesystem,bloodcells,retina,brain
3.Essentialstepsforaerobicpathway.
AEROBICOXIDATIONofcarbohydrates
Inexistenceofoxygen,glucosecanbethoroughlyoxidizedtocarbondioxideandwaterthrough4stages.
1.Glycolysispathway(inCytosol)
2.Pyr-decarboxylation(inmitochondria)
3.Tricarboxylicacidcycle(TCAcycle)
4.Oxidativephosphorylation
PDC
pyruvatedehydrogenaseComplex
Thesystemconsistof
3ENZYMS5COENZYMES
PyruvatedehydrogenaseTPP(B1),CoA
Dihydrolipoamidetransacetylaselipoicacid
DihydrolipoamidedehydrogenaseB2intheformofFAD
PPintheformofNAD+
TCA
Sum:
Acetyl-CoA+3NAD++FAD+GDP+Pi+2H2O————〉
2CO2+CoA+3NADH+3H++FADH2+GTP
Keyenzymeswithinpathways:
Step1:
condensation(缩合作用)/citratesynthase
keyenzyme1:
citratesynthase
Step3:
oxidativedecarboxylation/isocitratedehydrogenase
keyenzyme2:
isocitratedehydrogenase
coenzyme:
NAD+
Step4:
oxidativedecarboxylation/α-ketoGDC
keyenzyme3:
α-ketoGDC
coenzyme:
NAD+
ATP/GTP-producedpathways:
Step5:
substrate-levelphosphorylation/succinyl-CoAsynthetase
produce1GTP
H+-passedpathways:
Step3:
oxidativedecarboxylation/isocitratedehydrogenase
keyenzyme2:
isocitratedehydrogenase
coenzyme:
NAD+
Step4:
oxidativedecarboxylation/α-ketoGDC
keyenzyme3:
α-ketoGDC
coenzyme:
NAD+
Step6:
dehydrogenation/succinatedehydrogenase
coenzyme:
FAD
Step8:
dehydrogenation/malatedehydrogenase苹果酸
coenzyme:
NAD+
SignificanceofTCACycle
⏹Commonpathwayforcarbohydrate,lipid,andAAmetabolism;
⏹Muchfreeenergyareliberatedviadehydrogenation;
⏹Interconversionofmetabolitese.g.carbohydratetofattyacid;ureacycletoTCAcycle.
Energychangeintheaerobicoxidation
Stage1~3:
C6H12O6+6H2O+10NAD++FAD+4ADP+4Pi——〉
6CO2+10NADH+10H++2FADH2+4ATP
Stage4Oxidativephosphorylation
NADH+H++1/2O2——〉NAD++H2O2.5ATPx10=25
FADH2+1/2O2——〉FAD+H2O1.5ATPx2=3
Sumreactionofaerobicoxidation:
C6H12O6+6H2O+10NAD++FAD+4ADP+4Pi——〉
6CO2+12H2O+32ATP(or30ATP)
Regulationofaerobicoxidation
底物产物关键酶活性
Pastuereffect
⏹Aerobicoxidationinhibitstheanaerobicdegradationofglcucose.
⏹Explain:
inaerobic,ATPandNADHincrease,theyarenegativeeffectorsforPFK(keyenzymesinglycolysis),ADPandNADaspositiveeffectorsaredecreased.
Comparisionofglycolyticpathwayandaerobicpathway:
THEPENTOSE-PhosphateSHUNT
1.AnoxidativepathwayinwhichG-6-Pisdegradedtocarbondioxide,accompaniedbyreductionofNADPtoNADPH,followedbyacyclesetofreactionswhichregeneratetrioseandhexose.
2.Pathways
1ststage——DehydrogenationgiveNADPH(notNADH)andchangeHexose-PtoPentose-P.G6PD(G-6-Pdehydrogenase):
thekeyenzymeinchangingHexose-PtoPentose-P.veryimportantinunderstandingdruginducedhemolysis.ItscoenzymeisNADP(notNAD)
2ndstage——GrouptransferReactions:
interconversionbetween5C,3C,7C,4C,and6Csugars,catalyzedbyTransketolaseandTransaldolase,theircoenzymeconsistofTPP(B1).
3.Significance
A)BiosynthesisofnucleotideneedRibose.NucleotidesmakeupDNA,RNA.
B)NADPHas2Hdonorarerequiredin
1) Fattyacidandcholesterolsynthesis
2)HydroxylationreactionsinBiotransformationandconversionofcholesteroltocholicacids,steroidhormones.
3)MaintaintheformofGSH,protectionofPr,whichisthereasonfordruginducedhemolysis.BroadbeanDiseaseisaninbornerrorofG6PDdefficiencycommonlyseeninEastGuangdongpopulation.
GlycogenSignificance
⏹Glycogenisthestorageformofcarbohydrates
⏹Liverglycogencanbeusedassourcesofbloodglucose
⏹Muscularglycogengothroughoxidationpathwaysforenergysupply
Glycogen
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