Carbohydrate metabolism.docx

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