carbohydrates-中国医科大学-糖代谢-生物化学-英文

Chapter4CarbohydratesMetabolismThebiochemistryandmolecularbiologydepartmentofCMU§1Overview•Carbohydratesingeneralarepolyhydroxyaldehydesorketonesorcompoundswhichyieldtheseonhydrolysis.BiosignificanceofCarbohydrates•Themajorsourceofcarbonatomsandenergyforlivingorganisms.•Supplyingahugearrayofmetabolicintermediatesforbiosyntheticreactions.•Thestructuralelementsincellcoatorconnectivetissues.Glucosetransporters(GLUT)•GLUT1~5GLUT1:RBCGLUT4:adiposetissue,muscleThemetabolismofglucose•glycolysis•aerobicoxidation•pentosephosphatepathway•glycogensynthesisandcatabolism•gluconeogenesisglycogenGlycogenesisGlycogenolysisPentosephosphatepathwayRibose,NADPHlactateH2O+CO2starchLactate,aminoacids,glycerolglucose§2GlycolysisGlycolysis•Theanaerobiccatabolicpathwaybywhichamoleculeofglucoseisbrokendownintotwomoleculesoflactate.glucose→2lacticacid(lackofO2)•Alloftheenzymesofglycolysislocateincytosol.1.TheprocedureofglycolysisGpyruvatelacticacidglycolyticpathway1)Glycolyticpathway:G→pyruvateincluding10reactions.•PhosphorylatedGcannotgetoutofcell•Hexokinase,HK(4isoenzymes),glucokinase,GKinliver;•Irreversible.(1)Gphosphorylatedintoglucose6-phosphateOHOHHOHHOHHOHCH2HHOOHOHHOHHOHHOHCH2HOPATPADPHexokinaseMg2+GG-6-PhexokinaseglucokinaseoccurrenceinalltissuesonlyinliverKmvalue0.1mmol/L10mmol/LSubstrateG,fructose,glucosemannoseRegulationG-6-PInsulinComparisonofhexokinaseandglucokinase(2)G-6-P→fructose6-phosphateOHOHHOHHOHHOHCH2HOPG-6-PisomeraseOHCH2OHHCH2OHHHOHOOPF-6-P(3)F-6-P→fructose1,6-bisphosphate•Thesecondphosphorylation•phosphofructokinase-1,PFK-1OHCH2OHHCH2OHHHOHOOPF-1,6-BPOHCH2HCH2OHHHOHOOPOPATPADPMg2+F-6-PPFK-1(4)F-1,6-BP→2Triosephosphates•ReversibleF-1,6-BPCH2COCHHOCOHHCOHHCH2OPOPCH2COOPCHOCHOHCH2OPCH2OH+aldolasedihydroxyacetonephosphate,DHAPglyceraldehyde3-phosphate,GAP(5)TriosephosphateisomerizationG→2moleculeglyceraldehyde-3-phosphate,consume2ATP.CH2COOPCHOCHOHCH2OPCH2OHDHAPGAPphosphotrioseisomerase(6)Glyceraldehyde3-phosphate→glycerate1,3-bisphosphateCHOCHOHCH2OPNAD+NADH+H+Piglyceraldehyde3-phosphatedehydrogenase,GAPDHCCHOHCH2OPOO~Pglycerate1,3-bisphosphate,1,3-BPGglyceraldehyde3-phosphate(7)1,3-BPG→glycerate3-phosphate•SubstratelevelphosphorylationCOO-CHOHCH2OPCCHOHCH2OPOO~PADPATPglycerate1,3-bisphosphateglycerate3-phosphatePhosphoglyceratekinase(8)Glycerate3-phosphate→glycerate2-phosphateCOO-CHOHCH2OPCOO-CHCH2OHOPglycerate3-phosphateglycerate2-phosphateMutase(9)Glycerate2-phosphate→phosphoenolpyruvateCOO-CHCH2OHOPCOO-CCH2OPEP~P+H2Oenolaseglycerate2-phosphate(10)PEP→pyruvate•Secondsubstratelevelphosphorylation•irreversibleCOO-CCH3ADPATPCOO-CCH2OPEP~PpyruvatekinaseOPyruvate2)Pyruvate→lactateCOOCCH3NAD+NADH+H+OPyrCOOCHOHCH3Lactatedehydrogenase,LDHLacticacidSummaryofGlycolysisATPADPMg2+PFK-1GAPDHAPglycerate1,3-bisphosphateNADH+H+glyceraldehyde3-phosphatedehydrogenaseH3PO4NADH+H+NAD+ADPATPglycerate3-phosphateglycerate2-phosphateH2OPEPATPADPpyruvatekinaselactatepyruvateGG-6-PF-6-PF-1,6-BPNAD+PhosphoglyceratekinaseIsomeraseAldolaseMutaseEnolaseLDHHKATPADPMg2+Totalreaction:C6H12O6+2ADP+2Pi2CH3CHOHCOOH+2ATP+2H2OFormationofATP:Thenetyieldis2~Por2moleculesofATPperglucose.2.RegulationofGlycolysis•Threekeyenzymescatalyzeirreversiblereactions:Hexokinase,Phosphofructokinase&PyruvateKinase.1)PFK-1ThereactioncatalyzedbyPFK-1isusuallytherate-limitingstepoftheGlycolysispathway.Thisenzymeisregulatedbycovalentmodification,allostericregulation.bifunctionalenzyme2)Pyruvatekinase•Allostericregulation:F-1,6-BPactsasallostericactivator；ATPandAlainliveractasallostericinhibitors;•Covalentmodification:phosphorylatedbyGlucagonthroughcAMPandPKAandinhibited.ATPADPPKAGlucagonPyruvateKinase(active)PyruvateKinase-P(inactive)cAMP3)Hexokinaseandglucokinase•Thisenzymeisregulatedbycovalentmodification,allostericregulationandisoenzymeregulation.•InhibitedbyitsproductG-6-P.•Insulininducessynthesisofglucokinase.3.Significanceofglycolysis1)Glycolysisistheemergencyenergy-yieldingpathway.2)GlycolysisisthemainwaytoproduceATPinsometissues,eventhoughtheoxygensupplyissufficient,suchasredbloodcells,retina,testis,skin,medullaofkidney.•Inglycolysis,1molGproduces2mollacticacidand2molATP.§3AerobicOxidationofGlucose•TheprocessofcompleteoxidationofglucosetoCO2andwaterwithliberationofenergyastheformofATPisnamedaerobicoxidation.•ThemainpathwayofGoxidation.1.ProcessofaerobicoxidationGPyrcytosolMitochodriaglycolyticpathwaysecondstagethirdstageCO2+H2O+ATPPyrCH3CO~SCoAfirststageTAC1)OxidativedecarboxylationofPyruvatetoAcetylCoA•irreversible;•inmitochodria.COO-CCH3NAD+NADH+H+OpyruvateCH3CPyruvatedehydrogenasecomplexAcetylCoAO~SCoA+HSCoA+CO2Pyruvatedehydrogenasecomplex:E1pyruvatedehydrogenaseEsE2dihydrolipoyltransacetylaseE3dihydrolipoyldehydrogenasethiaminepyrophosphate,TPP(VB1)HSCoA(pantothenicacid)cofactorslipoicAcidNAD+(Vpp)FAD(VB2)HSCoANAD+Pyruvatedehydrogenasecomplex:ThestructureofpyruvatedehydrogenasecomplexSSCHH2CH2C(CH2)4COOHSHSHCHH2CH2C(CH2)4COOH+2H-2HlipoicaciddihydrolipoicacidCCNH2HCNCH2SCCNCNCHCH3CH2CH2H3COPOO-OPOO-O-+TPPHSCoAHSCH2CH2NHCCH2OCH2NHCCOOHHCCH2CH3CH3OPOOHOPOH