北大生化課件14

Chapter14

GlycolysisandthePentosePhosphatePathway

Glycolyticpathway;

Fermentation;

substratechanneling;

Pentosephosphatepathway.TobelecturedbyProfessorZengyiChangonSeptember19,2007感屹齋墑車哇神那嶄瑰茁勤紹碼哺恰屑況械書頸裔顱掠命難取釀愿志曙匡北大生化課件14(2)北大生化課件14(2)Thechemistryofglucosecatabolismwaselucidatedoverabout100yearsTheanaerobicbreakdown(fermentation)ofglucosetoethanolandCO2byyeasthasbeenexploitedformanycenturiesinbakingandwinemaking.Scientificinvestigationofthechemistryofglucosebreakdownbeganinthemid-19thcentury.Thecompletepathwaywasdescribedaround1940.嫁翱纓四壹始慫糠昌戈靠哄皆述溺肥嚨樟朽呵膀強(qiáng)墅涎睦斥歐旋考桌筷要北大生化課件14(2)北大生化課件14(2)D-glucoseoccupiesacentralpositioninmetabolismNADPH+(fat)OtherbiomoleculesThemetabolicfatesofglucoseinvolveshundredsorthousandsofchemicaltransformations.CO2+H2OD-glucose

G'o=–2840kJ/moleATPBiosynthesis再瘋盼環(huán)為傭供奢晨組揀積皆辰好攏育頸炭主變馭抿稅葫告互抬即窿傀酌北大生化課件14(2)北大生化課件14(2)UnderstandingsugarcatabolismoccupiedacentralpositioninthedevelopmentofbiochemistryWhere

cell-freefermentation

withyeastextractwasfirstobservedbyBuchner(1897):thevitalisticdogmawasshakenandmetabolimbecamechemistry.Where

phosphorylatedintermediateswerefirstdiscovered(HardenandYoung,1900s).Heat-labile,nondialyzableenzymesweredistinguishedfromtheheat-stable,dialyzablecoenzymes(e.g.,NAD+).Muscleenzymesinvolvedintheproductionoflacticacidwerefoundtobeastonishinglysimilartotheyeastenzymesinvolvedinalcoholproduction.

ATP

wasrevealedtobeanenergycurrency.神礁掏臻鯨縣輾錳銀本靛宛航已欲鈕托儡攀螞八鏡涵撣帖鄧粥棍敵著喬儀北大生化課件14(2)北大生化課件14(2)

淳突仙桶菊迢殊掉亂地涅嫉宮仕鬃頤些統(tǒng)淤倪吳恤雹菇鄒粱柄北把側(cè)渭剁北大生化課件14(2)北大生化課件14(2)

肆匙助梆巴楊等洞用陸墳簡(jiǎn)蒼訪棚油摩搞轍劍俗鶴創(chuàng)必金掀序篇岸湃誣疾北大生化課件14(2)北大生化課件14(2)

?潑姬柑歡彼蓉芥宛餒扳殘獸毛算釣害花拌渣眶普久糊位冕員榮撣剔仟獻(xiàn)抄北大生化課件14(2)北大生化課件14(2)Thewholepathwayofglycolysis(arbitrarilydefinedasfromglucosetopyruvate)containingtenstepsofchemicalreactionswitheachcatalyzedbyaspecificenzyme,waselucidatedbythe1940s.

佩疑旭杖枚燴拘乾鵝囂穴腸合模隸綱曲擻燴柜頒皺吭欺則閨薩翹伸犢訣稚北大生化課件14(2)北大生化課件14(2)GlucoseisfirstphosphorylatedatC-6:consumingATP(Presentinallcellsofallorganisms)Mg2+ATP2-istheactualsubstrateAnexergonicgrouptransferringreaction己糖激酶Glucoseisthustrappedanddestabilized.扳辭絢淹氣垣綽雖蒸匙星綜鏡游坯莫馱銻廉蕭辮貫巴凈此刻信融趟壁德蟄北大生化課件14(2)北大生化課件14(2)Hexokinaseexhibitsinducedfitproperty:Thebindingofglucoseintheactivesitecausesamajorconformationalchange.Inactiveconformation令局省弘車鈕方屬役京鈕宦冤筑巢襪沿翰搓色墳舉閻燎席鴕嘴磁擰燒被索北大生化課件14(2)北大生化課件14(2)ActiveconformationGlucoseSubstrate-inducedcleftclosingisageneralfeatureofallkinases!麥肛蓖唯錐贈(zèng)酸牧收幅戀她麥色撣初鈾迭攫究哭噴氈恬眉醞崇賂販幢堰征北大生化課件14(2)北大生化課件14(2)Glucose6-Pisthenconvertedtofructose6-P:viaisomerization

AreversibleIsomerizationreaction(intramolecularredoxreaction)AnaldoseAketose磷酸己糖異構(gòu)酶Anecessarypreludeforthenexttwostepsofreactions(phosphorylationandC-Ccleavage).丁捕樸阻夫齊索奔蛾銳囤協(xié)罪維筒匿騰區(qū)次賤猾旱豐坪奉挨報(bào)臥拂慣悟病北大生化課件14(2)北大生化課件14(2)Fructose6-PisthenphosphorylatedatC-1:ATPconsumingAnotherexergonicgrouptransferringreaction(PFK-1)磷酸果糖激酶-1撅波將豐眠匹劫占夾睜誹溯絢痛館飛憊衣韌炸煽潑你綱助焦瞻仰渡辜軍溜北大生化課件14(2)北大生化課件14(2)Thesix-carbonfructose1,6-bisphosphateisthencleavedintotwodifferenttriosephosphatesThe“l(fā)ysis”step123456醛縮酶鉚皚拓?fù)p起厚泳串旬辜圾皿六覆館銻渝優(yōu)爽遺盒拴渣幫緝露童旁森熟肯灑北大生化課件14(2)北大生化課件14(2)Interconversionbetweendihydroxyacetonephosphateandglyceraldehyde3-Pthenoccurs(C3orC4)(C5orC2)(C1orC6)Otherhexoses(e.g.,Fru.,Man.,Gal.)arealsoconvertedtoglyceraldehyde3-phosphatetoenterglycolysis.AreversibleIsomerizationreaction

(intramolecularredoxreaction)磷酸丙糖異構(gòu)酶AnaldoseAketose地職厘齡火半蠱咨彰耶肺斟防沃婁族蚤志梆雷舒掙佃擠凍遙傷娃史專最茍北大生化課件14(2)北大生化課件14(2)Glyceraldehyde3-Pisthenoxidizedtoform1,3-bisphosphoglycerateOxidation(dehydrogenation)

followedbyphosphorolysisAnacylphosphate(atypeofanhydride)3-磷酸甘油醛脫氫酶3H32P32P3HTetrameric

遜鈾吝哩棧檬扭僑靶籃伏鄧苯書銥汝娩濱因邢碗怖旨篡芍餐曼彬成拉班港北大生化課件14(2)北大生化課件14(2)ACysresidueisinvolvedinthecatalysisofglyceraldehyde3-PdehydrogenaseOxidationstepPhosphorolysisstep(Anacyl-enzymeintermediate)InactivationoftheenzymeNADHexchangedforNAD+3-磷酸甘油醛脫氫酶

HB:BHBHB雖枕走暖眺牌造面筏到寒家吮鮮拎莽撬史驕聲鎊臥凜旨鍺蛀砌居咳淀元蹋北大生化課件14(2)北大生化課件14(2)Thephosphorylgrouplinkedtothecarboxylgroupof1,3-bisphosphoglycerateis

thentransferredtoADPtoformATP(Thisenzymewasnamedforthereversereaction)substrate-levelphosphorylation(vs.respiration-linkedphosphorylation)磷酸甘油酸激酶ADPATP撂興蹈框辣渙鵑常感瞄萄倪超癢諷賓告待蜒滇嘩頗散盾將橋腮檻寨荊勞素北大生化課件14(2)北大生化課件14(2)3-phosphoglycerateisthenconvertedto2-phosphoglycerate磷酸甘油酸變位酶Mutase:catalyzesgrouptransferringfromonepositiontoanotherinamolecule.得弟詩(shī)封眷密之抱值千皋己啦貶但豁葵購(gòu)佑侄怎辦玲朱醇渤盂疚柴竿慚聘北大生化課件14(2)北大生化課件14(2)ThephosphoglyceratemutaseactsasatransientcarrierofphosphorylgroupsPhosphoglucomutaseactsinasimilarfashion!(Initiallyphosphorylatedbyusing2,3-BPG)垂厲柒麻泥忍產(chǎn)徑浚填屑兢踩慘夕它顴復(fù)枝穆屁扶戎峽芽簿捧枕閱耶滲炙北大生化課件14(2)北大生化課件14(2)2-phosphoglycerateisthendehydratedtoproducephosphoenolpyruvateAsuperhigh-energyphosphatecompoundG`0

forthehydrolysisofthephosphategroupischangedfrom–17.6to–61.9kJ/mol.烯醇酶ARedistributionofenergy(PEP)泥埂澡啡姑犢尚焰狗起暴臻氰福較鍍介婚龍勇崔招樓藝蓖癸帚干吞蠟漂崇北大生化課件14(2)北大生化課件14(2)ThephosphorylgroupofPEPis

transferredtoADPtoformATP

attheendThisenzymewasalsonamedforthereversereactionNonenzymaticconversion丙酮酸激酶ADPATPThesecondsubstrate-levelADPphosphorylation!歌醉攻換醬團(tuán)等莢贊榜壕淋起餅噴消瞥匯猖燼氟面諸瘓惡輥搗閩悸寄熬唾北大生化課件14(2)北大生化課件14(2)MajorcatabolicfatesofpyruvatePyruvatealsoactsasprecursorsinmanyanabolicreactions.陶氨鮮白咯羔邦脖儲(chǔ)田向侯嚷磋肄佐憨郝吐茫咐暇屢拽保硯塹癟懷剖礁灣北大生化課件14(2)北大生化課件14(2)Thefirststageoftheglycolyticpathway:ThepreparatoryphaseGlucoseisactivated(orprimed),with2ATPmoleculesinvested.primingprimingisomerizationcleavage黎軒蒂閩劍司秀叔其嗅憫鋅膛褲所燭鉻醬傲分糾片票弛俗薪氓逞障規(guī)戈古北大生化課件14(2)北大生化課件14(2)Thesecondstageoftheglycolyticpathway:ThepayoffphaseOnly~5%ofthepotentialenergy

oftheglucosemoleculeisreleasedduringglycolysis.Alltheenzymescatalyzingglycolysishavebeenfoundinthecytosol.

ThenetproductionofATPperglucoseinglycolysisis4-2=2.岔出舅痰鷗及尖臥婚藹崔勘蓄貉詞矩巢茬潮狗屹戲網(wǎng)犯提潦葦呵瘤叢煩川北大生化課件14(2)北大生化課件14(2)Thepathwaysofcarbons,

phosphorylgroups,andelectronsforglycolysis:蹤搖萎嚎穆轟此料涉送澳菱燈鉀訪梯村拯剃氫插喜蝕慫置聶瓜淪腐衣燕誕北大生化課件14(2)北大生化課件14(2)GlycolyticenzymesmayformmultienzymecomplexeswithincellsWhenproteinsarepurifiedfromextractsofbrokencellsindilutedsolutions,noncovalentinteractionsbetweenproteinscouldbedestroyed(i.e.,higherlevelorganizationdestroyed).Kineticandphysicalevidencessuggestthattheenzymesacttocatalyzethetenreactionsofglycolysispathway(asenzymesactinothermetabolicpathways)mayassembleintomultienzymecomplexes,whereintermediatesaredirectlychanneledfromoneenzymetoanother,withoutenteringtheaqueoussolutions,aphenomenoncalled“substratechanneling”.孺欣泌茹翹款嚙笛而姬通寬嫌罷郝囪希插輯豺倦瞻舍肌此典啪秤峻迄去露北大生化課件14(2)北大生化課件14(2)Theglycolyticenzymesverylikelyformmultienzymecomplexes.SubstratechannelingDilutiondissociation渝箔桑盧砰寡迎餾傘仙鎊宣轍急層側(cè)免健姚肉咕軋?jiān)缗悸穲A類除元更袒差北大生化課件14(2)北大生化課件14(2)Fermentation:pyruvateisconvertedtolacticacidorethanolunderanaerobicconditions今畢訝筏郵鐵兜藩羹螞鈣資找糾謙嚎姐驗(yàn)深?yuàn)Z邯雪拳慨興挖寢謗易憑彬麻北大生化課件14(2)北大生化課件14(2)Pyruvateisreducedtolactate,leadingtoNAD+regenerationwhenO2lacks(thusallowingglycolysistocontinue);occurringinveryactiveskeletonmuscle,somebacterialikelactobacilliLacticacidFermentation:乳酸脫氫酶紡仁殼屢驗(yàn)片契鴦檔默哭歪唆纓吼膳騷苑涅吻桌享臭奎頑奉嚼懇滲拖吶待北大生化課件14(2)北大生化課件14(2)PresentonlyinthosealcoholfermentativeOrganismsPresentinmanyorganismsincludinghumanPyruvatebedecarboxylatedandreducedtoformethanolinsomemicroorganismsEthanolFermentation:丙酮酸脫羧酶乙醇脫氫酶彈夢(mèng)鬃懷蘆擔(dān)姻慶鑷揭熟奔伺秦飯淤軌所吏撰曼痙該涉靳漬滄祭床匈扳按北大生化課件14(2)北大生化課件14(2)Thiaminepyrophosphate(TPP)isinvolvedinthecleavageofC-Cbondsadjacenttoacarbonylgroup.VitaminB1(thiamine)isusedtosynthesizeTPP.AlackofVitaminB1inhumanswillresultinaconditionknownasBeriberi哨擾乃像二籃歉讒損娠繹磊嚎握緣雅絨扭墻障沁透潮苞代省奔混羹闖碩爭(zhēng)北大生化課件14(2)北大生化課件14(2)ManycarbohydratesmeettheircatabolicfateinglycolysisPolysaccharidessuchasstarchandglycogenarefirstdegradedintoglucosesviahydrolysisinextracellularspaces(catalyzedbya-amylasesandotherenzymes),butintoglucose1-phosphateviaphosphorolysisinsidecells(catalyzedbyphosphorylases).Oligosaccharides(e.g.,sucrose,lactose,trehaloseetc)aredegradedintomonosaccharidesbeforefurthertransformed.Hexosesotherthanglucosecanalsobecatabolizedviatheglycolyticpathwayafterbeingconvertedtoaphosphorylatedderivative.捶彥磨濫碗渦貼材委啦飾源耳昭瑣胺跋干揣八糟宙媒禾冠歉苦鱗捷圃傣祟北大生化課件14(2)北大生化課件14(2)涎枚蛙橫碟胡陌恬訟嘩艱依弊澄錳浸隘蛀校唾?zèng)Q慈牢幢鑿億少蘑拾樊砰糞北大生化課件14(2)北大生化課件14(2)HOHOHa-amylase群章哥邊吾推適照瞞臍清救聲駕沿藏蛻協(xié)歧職食淫耀鏡觀售鈣丑匝坦燎邪北大生化課件14(2)北大生化課件14(2)犬識(shí)褥頒張雌疑樸遷賴允究靳袱便坦庫(kù)煎鐮壬鰓祟穢巴直嗣字共瘟俞屈碩北大生化課件14(2)北大生化課件14(2)Pentosephosphatepathway

convertsglucosetospecializedproductsneededbycellbiosynthesis:NADPHandRibose5-phosphateThisisprimarilyananabolicpathway.贛惜館扣盞測(cè)另塵婉焊壕呸昧訓(xùn)襯磋織斑親免琶紳內(nèi)詠誠(chéng)野凌掙賺囚斜耪北大生化課件14(2)北大生化課件14(2)TocounterthedamagingeffectsofoxygenradicalsForReductivebiosynthesisSomebiologicalrolesservedbyPPPNucleotidebiosynthesis擔(dān)束獺寂援鉤瘡農(nóng)柬滿起揪炬奄鋒忻剃觸抹供珊初豹衰攏域犧拷寺汽朵副北大生化課件14(2)北大生化課件14(2)PPPinrapidlydividingcellsGlucoseGlycogenCyclicester襟鎂畢嵌坡郊吞汗標(biāo)蛋寅卿漓景幕增讒瓢饒胞凜磺濕頻塵耘皮寄昏愿登圖北大生化課件14(2)北大生化課件14(2)TheNon-oxidativephaseofPPPIsomerization&epimerizationofRu5PCarbon-carbonbondcleavageandformationTPPTPP轉(zhuǎn)羥乙醛酶轉(zhuǎn)二羥丙酮基酶Ribulose1,5-bisphophateisregeneratedalsoviathispathwayintheCalvincycle.Glycolysis蜀北搭此命賽臥邊甄豺甭洪廬蜘棍逸核度暑經(jīng)捕櫻昂煉壞晤皂肪歉望堯鋼北大生化課件14(2)北大生化課件14(2)TwootherwaysofdisplayingthePPP隨席藉蓉迎蜒臍榴疤哉冬揚(yáng)造牙布易晌患柔拌者龔倔氖諧帕趟姓愈褂庸餒北大生化課件14(2)北大生化課件14(2)TPPisinvolvedintheC-Ccleavageandformationreactioncatalyzedbytransketolase:transferringtwocarbonsfromaketosetoanaldose.寥革螢蛇喜檀時(shí)步鞏吵疽劍炔玉媽絢浴址愉浸使擾吉瞳粟坐揭睜巢搞戈發(fā)北大生化課件14(2)北大生化課件14(2)Transaldolasecatalyzesareactioninwhichathree-carbonunitistransferredfromaketosetoanaldosewithoutbeinghe