-《生物化学Biochemistry》双语课件-06-维生素Vitamin-and-Coenzyme

Chapter6VitaminandCoenzyme2023/7/251Vitaminsareorganicmoleculesthatareessentialtothebiologicalprocessesofhigherorganisms,butcannotbesynthesizedbytheseorganisms.Fat-soluble:vitaminsA,D,E,andKWater-soluble:Bcomplexvitamins，lipoicacidandvitaminC.2023/7/252Vitaminfunctions:Coenzymesincatalyzedreactions(derivatesofvitaminBs)Somevitaminsareconsideredashormones(vitaminsA&D)Antioxidants(vitaminsC&E)2023/7/253Avitaminosis

维生素缺乏症:beinglackofvitamin,obstacleofmetabolismdifferentvitamin,differentphysiologyfunction,differentsymptom2023/7/254Lipid-SolubleVitamins

Thefourlipid-solublevitamins-A,D,E,andK

类异戊二烯分子(异戊二烯构建分子生物合成)Althoughoneofthese,VitaminD,isultimatelyderivedfromcholesterol,Existedwiththelipidinfoods.AbsorbedintheintestineswiththelipidStoredinthebody,especiallyintheliver2023/7/255Afatsolublevitamin,Derivedfromβ-carotene胡萝卜素VitaminA2023/7/256ThealcoholformofvitaminA,retinol视黄醇,isthestorageforminthebodyThealdehydeform,retinal视黄醛,hasaroleinvision.Theacidform,retinoicacid视黄酸,functionsinembryonicdevelopment.VitaminAactstosomeextentinthebodyasanantioxidant抗氧化剂,protectingagainstoxidativedamage2023/7/257LackofVitA,暗处不能辨别物体,夜盲症眼球视网膜两类感觉细胞圆锥细胞:sensitivetobrightlightandcolour

杆细胞:sensitivetoweaklight,暗视觉视紫红质全反型视黄醛视蛋白11-顺视黄醛光分解暗合成同分异构酶2023/7/258VitaminD抗佝偻病维生素derivedfromcholesterol2023/7/259D3(mostabundantform),cholcalciferol胆钙化醇,inamimal

D2,麦角钙化醇,inplantVitaminDisnottechnicallyavitamin（notrequiredinthediet.Itarisesfromuv-photolysisof7-dehydrocholesterol7脱氢胆甾醇）VitaminDregulatescalciumandphosphorusmetabolism,有利于新骨的生成与钙化。2023/7/2510VitaminEAfatsolublevitamin,alsocalledα

-tocopherol生育酚,与动物生育有关2023/7/2511Anantioxidantprotectagainstoxidativedamageincellularmembranes.preventingtheattackofperoxides过氧化物,过氧化氢onunsaturedfattyacidsinmembranelipidsDeficiencyofvitaminEalsoleadstoothersymptoms,vitaminEprobablyplaysotherrolesasyetundiscovered.2023/7/2512inplantsasvitaminK12-甲基-1,4-萘醌的衍生物inanimalsasvitaminK2一般不易缺乏凝血维生素：具有促进凝血的功能促进肝脏合成凝血酶原(凝血因子II),调节另外三种凝血因子VII,IX,X的合成vitaminK2023/7/2513VitaminK2(Menaquinone)inanimalsVitaminK1(Phylloquinone)

inplants2023/7/2514Water-solublevitaminsthiamin(B1)硫胺素riboflavin(B2)核黄素niacin,niacinamide(PP,B3)烟酰(胺)pantothenicacid(B5)pyridoxin,pyridoxal(B6)biotin(B7)cyanocobalamin/hydroxycobalamin(B12)folicacid/folate(B9,VitaminM)lipoicacid/lipoate硫辛酸ascorbicacid(C)B-complexvitamins2023/7/2515CoenzymesSomeenzymesmayrequirethehelpofsomeothersmallmoleculeoriontocatalyzeareaction,Likeenzymes,coenzymesarenotirreversiblychangedduringcatalysis;theyareeitherunmodifiedorregenerated.Eachkindofcoenzymehasaparticularchemicalfunction.Someareoxidation/reductionagents,somefacilitategrouptransfers,andsoforth.Thenumberofimportantcoenzymesislimited,buteachofthemmaybeassociatedwithmanydifferentenzymes.2023/7/2516interconvertingUDP-glucoseandUDP-galactoseThemechanism:thehydroxylatposition4ischangedinstereochemicalorientationinvolvesoxidationofthehydroxyltoacarbonyl羰基asanintermediatestate.Carbonylintermediate-----excellentintermediatestateforinterconversionofthesugarsNAD+andNADHneverleavetheenzyme,theyarereducedandreoxidizedinacyclicfashion,providingatemporaryrestingplaceforelectronsandthehydrogenfromthesubstrate.2023/7/2517腺苷钴氨素甲基钴氨素2023/7/25181.VitB1&ThiaminePyrophosphate(TPP)焦磷酸硫胺素,辅羧酶含硫的噻唑环thiazole含氨基的嘧啶环pyrimidine

抗脚气病维生素twoheterocyclicrings2023/7/2519Mechanismofaction–

TPP：thiazoleisthereactivemoiety,carbanion

负碳离子.

Carbanion

canattackthecarbonylcarbonofa-ketoacids,suchaspyruvate,givinganadditioncompoundTPPisusedasacoenzymeforalldecarboxylationsof-ketoacidsthiamine(VitaminB1)+ATPpyrophosphategroupTPP+AMPa2023/7/2520羟乙基-TPP2023/7/25211.Carbanionattackonthecarbonyl-carbonofa-ketoacidstoyieldanadditioncompound

加成化合物2.Decarboxylationoftheadditioncompoundwiththethiazoleringactingasanelectronsinkinformingaresonance-stabilizedeneamine.3.Protonationoftheeneaminetoformanactiveacetaldehydecalledhydroxyethyl-TPP.4.Thedecarboxylatedcompoundisreleased,yieldingfreeTPP.5.Carbanionformation羟乙基-TPP2023/7/2522

pyruvate

decarboxylase

丙酮酸脱羧酶,pyruvate

dehydrogenase丙酮酸脱氢酶,branchedchaina-ketoaciddehydrogenase

glutarate

dehydrogenase酮戊二酸脱氢酶Transketolase

转羟乙醛酶,转酮醇酶.,SomeenzymesthatuseTPP:2023/7/2523维生素B1缺乏,糖代谢受阻,丙酮酸积累血、尿、脑组织丙酮酸含量增多，出现多发性神经炎，皮肤麻木，心力衰竭，肌肉萎缩。下肢浮肿等脚气病2023/7/2524nicotinamide烟碱coenzymes

nicotinamideadeninedinucleotide(NAD+)

nicotinamideadeninedinucleotide

phophate(NADP+)2.VitPP抗癞皮病维生素烟酸nicotinicacid烟碱nicotinamide2023/7/2525NADHisacarrierofelectronsproducedinbiologicaloxidations.twoformsNADH----reducedformofthemolecule(carrieselectrons)

NAD+-----oxidizedformofthemolecule(lackselectrons)2023/7/2526NADPHisanelectroncarrier.Twoforms:NADPH----reducedformofthemolecule(carrieselectrons)

NADP+-----oxidizedformofthemolecule(lackselectrons)NADPHisproduced-------pentosephosphatepathwayInplants,photosynthesisisanothersourceofNADPH.2023/7/2527NADHVSNADPHNAD+/NADH:donateselectronstotheelectrontransportsystemforenergygeneration氧化途径（分解代谢）中电子受体NADP+/NADPH:donateselectronstobiosyntheticreactions还原途径（合成代谢）电子供体2023/7/25283.Riboflavin核黄素

核醇ribitol

7，8－二甲基异咯嗪isoalloxazinering

Riboflavin(vitaminB2),isacomponentoftheflavincoenzymes,FADandFMN2023/7/2529SiteN1andsiteN5hasactivedoublebondrespectively2023/7/2530FADisanimportantacceptorofelectronsFADistheoxidizedformofthemolecule(lackselectrons).

FADH2isthereducedform(carrieselectrons)Flavincoenzymes:flavinadeninedinucleotide(FAD)

flavinmononucleotide(FMN)2023/7/2531

FADandFADH2functioninmanyoxidationreactionsSuccinate+FAD(enzymebound)<=>Fumarate+FADH2(enzymebound)FADisboundcovalentlytotheenzymeproteinthroughaspecifichistidineresidue2023/7/2532Theabilityoftheringsystemofriboflavintoexistasasemiquinoneallowstheflavincoenzymestoacceptelectronseithersinglyorinpairs2023/7/2533CommonacceptorsofelectronsincludetheFAD,FMN,NAD+,NADP+NAD+,NADP+canacceptelectronsinpairs,eachpairofelectronsfromNADHresults2.5ATPsFADandFMNcanalsoacceptsingleelectronsviaformationofasemiquinoneintermediate,

eachpairofelectronsdonatedbyFADH2resultsin1.5ATPs2023/7/25344.PantothenicacidandCoenzymeA(CoAorCoASH)

Pantothenicacid

coenzymeA----acyl-carriermoiety2023/7/2535β

-Mercaptoethylamine巯基乙胺----acylgroupsareattached2023/7/25363`,5`-ADPAfreethiolisthefunctionallysignificantpartofthecoenzymemoleculeTherestofthemoleculeprovidesenzymebindingsites3`,5`-ADP:识别部位,增加CoA亲和性和专一性2023/7/2537acylatedderivatives,suchasacetyl-coenzymeA,theacylgroupislinkedtothethiolgrouptoformanenergy-richthioestertheacylatedformsofcoenzymeA:acyl

-

CoA,CH3CO-SCoAtheunacylatedform:CoA-SH.2023/7/2538energy-richnatureofthioestersVSordinaryesters2023/7/2539CommonmetabolicreactionsinvolvingCoenzymeAareshownbelow.1.

Acetate+CoASH+ATP<=>Acetyl-CoA+AMP+PPi

(catalyzedbyAcetateThiokinase硫激酶).2.

Pyruvate+NAD++CoASH<=>Acetyl-CoA+NADH+CO2(catalyzedbyPyruvate

Dehydrogenase)3.

3-Ketoacyl-CoA+CoASH<=>Acyl-CoA(less2carbons)+Acetyl-CoA(catalyzedbyThiolase硫解酶).2023/7/25404.

Malonyl-CoA+ACP<=>Malonyl-ACP+CoASH(catalyzedbyMalonyl-CoA-ACP

Transacylase)5.

Acetyl-CoA+ACP<=>Acetyl-ACP+CoASH(catalyzedbyAcetyl-CoA-ACPTransacylase)6.

Acyl-CoA+Carnitine<=>Acyl-Carnitine+CoASH(catalyzedbyCarnitine

AcyltransferaseI)7.

Acyl-Carnitine+CoASH<=>Acyl-CoA+Carnitine(catalyzedbyCarnitine

AcyltransferaseII)肉(毒)碱2023/7/25415.VitB6&PyridoxalPhosphate(PLP)VitB6吡哆醛嘧啶衍生物吡哆醇吡哆胺活性形式：磷酸吡哆醛（PLP)氨基酸代谢中多种酶的coenzyme

磷酸吡哆胺2023/7/2542Pyridoxalphosphateparticipatesin

transaminations

转氨作用,

decarboxylations

去碳酸基,numerousmodificationsofaminoacidsidechains2023/7/2543PLP-containingenzymesfunction:SchiffbasebetweentheaminoacidandcoenzymeAcation(ametaloraproton)isessentialtobridgethephenolateionofthecoenzymeandtheimino

亚氨基的nitrogenoftheaminoacid.Thisbridgingmaintainstheplanarityofthestructure,essentialforcatalysis.2023/7/2544aquinoid

醌型structureDependingonthebondlabilized

使不稳定,formationofthealdimine

醛亚胺canleadtoatransamination,todecarboxylation,toracemization,ortonumeroussidechainmodifications2023/7/25456.VitaminB12Thepresenceofcobaltandamidenitrogens-----thenamecobamidesorcobalamins

钴胺素,钴胺酰胺2023/7/2546Themetalcobaltiscoordinatedcorrinring咕啉环,Thecyanide氰化物attachedtothecobalt辅酶：5`－脱氧腺苷钴胺素甲基钴胺素About15differentB12-requiringreactionsareknown核苷酸还原成脱氧核苷酸isomerizationsmethylgrouptransfer2023/7/2547B12coenzymes

methylgroup5'-adenosylmoietyCNlinkedtocobaltthefirstknownorganometallicsvitamininmetabolism2023/7/2548thesynthesisofmethionine

甲硫氨酸fromhomocysteine高半胱氨酸2023/7/2549B12-requiringreactionsinvolve:(1)methylgrouptransfer(2)核苷酸还原成脱氧核苷酸byaribonucleotide

reductaseofLactobacillus乳酸菌.(3)isomerizations：exchangeacarbon-boundhydrogenwithanothercarbon-boundfunctionalgroup甲基丙二酰-CoA2023/7/25507.Biotin

噻吩环双环化合物尿素戊酸Biotin2023/7/2551Biotinisavitaminandacoenzymelinkedcovalentlytocarboxylaseenzymesthroughtheε-aminonitrogenoflysine生物胞素复合物associatedwithenzymesperformingcarboxylationreactions2023/7/2552Enzymescontainingbiotin：acetylCoA

carboxylaseAcetyl-CoA+ATP+HCO3-<=>Malonyl-CoA丙二酸单酰～

SCoA+ADP+Pi+H+pyruvate

carboxylasePyruvate+HCO3-+ATP<=>Oxaloacetate+ADP+Pi+H+

Carbamoyl

氨基甲酰phosphatesynthetaseIIGlutamine+ATP+HCO3-<=>Glutamate+CarbamoylPhosphate+ADP2023/7/2553Biotin--abundantinmanyfoodsandissynthesizedbyintestinalbacteriadeficiencyisrare,butcausedbyadietrichinraweggsEggwhitescontainalargeamountoftheproteinavidin

(Mr70,000),whichbindsverytightlytobiotinandpreventsitsabsorptionintheintestine.Theavidinofeggwhitesmaybeadefensemechanismforthepotentialchickembryo,inhibitingthegrowthofbacteria.Wheneggsarecooked,avidinisdenatured(andtherebyinactivated)alongwithallothereggwhiteproteins.Avidin--------biotin(Aproteincovalentlybound)affinitychromatography2023/7/2554碟酸碟酰谷氨酸6－甲基碟啶对氨基苯甲酸8.FolicAcid(Pteroylglutamicacid碟酰谷氨酸)

吡嗪2023/7/2555Folicacidisformedfromthreedistinctmoieties:(1)6-methylpterin6－甲基喋啶(2)p-aminobenzoicacid(PABA),对氨基苯(甲)酸

(3)glutamicacid

3-8ormoreglutamateresiduespermoleculeofvitamin2023/7/2556folate----------------activeforms(tetrahydrofolate)dihydrofolate

reductase(DHFR)--NADPH-specificenzyme2023/7/2557tetrahydrofolate---------generationandutilizationofsingle-carbon

methyl甲基,

methylene

亚甲基,

formyl甲酸基N5,N10orboth--single-carbon

2023/7/25582023/7/2559ActivityofDHFRisblockedbyfolateanalogs

aminopterin

氨碟呤

amethopterin氨甲碟呤抗肿瘤药物嘌呤&胸腺嘧啶肿瘤生长氨碟呤氨甲碟呤2023/7/2560FolicaciddeficiencyDNAsynthesisCelldivisionisslow,volumeincreasemegaloblasticanemia巨红细胞性贫血2023/7/25619.lipoicacid闭环二硫化物形式开环还原形式Lipoic

acid+Lys

硫辛酰胺复合物lipoamideanamidebondlinkingthecarboxylgroupoflipoicacidtoalysineδ-aminogroupoftheenzyme.2023/7/2562LipoicacidinamidelinkagewithaLysresidue2023/7/2563Lipoate

Twothiolgroups-----reversibleoxidationtoadisulfidebond(-S-S-)

electronhydrogencarrieracylcarrier2023/7/25642023/7/256510.VitaminC(AscorbicAcid)

awater-solubleenzymeacidicactsasapotentantioxidant,protectingagainstdamagebyreactiveoxygenspecies(2,3site---OH)L-ascorbicAciddehydro-ascorbate22023/7/2566AntioxidantssuchasvitaminA,vitaminC,andvitaminEprovideprotectionagainstoxidativedamagefromreactiveoxygenspecies,suchassuperoxides,hydroxylradicals,hydrogenperoxide.2023/7/2567

aroleinmakingcrosslinksbetweenaminoacidsincollagen胶原蛋白VitaminCCollagenfibers----formthematrix,orcement,materialinbone,onwhichthemineralconstituentsprecipitate.animportantconstituentoftendonsandskin2023/7/2568Collagen:widespreadmodification

prolinetohydroxyproline

lysine

tohydroxylysineThehydroxylation羟基化作用reactionsincollageninvolvevitaminC羟化酶维持活性所必需的辅因子2023/7/2569prolyl4-hydroxy