代谢工程 英文原版PDF Chapter 12 - Analysis of Structure of Meta

代谢工程 英文原版PDF Chapter 12 - Analysis of Structure of Meta

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时间:2019-05-25

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1、CHAPTER12AnalysisofStructureofMetabolicNetworksInthepreviouschapter,wereviewedthebasicconceptsofMetabolicControlAnalysisandmethodsforthedeterminationofitskeyparameters.ItwasnotedtherethattheframeworkofMCAprovidesthemeansofquantify-ingthedegreeofcontrolexertedbyeachindividualreactionstepina

2、metabolicnetworkuponeachnetworkfluxandmetabolite,intheformofcontrolcoefficients.Ineffect,controlcoefficientsprovideacharacterizationoftheeffectsresultingfromtheperturbationofaparticularreaction,sothattheeffectsofotherperturbationsinthatsamestepcanbepredicted.ThemethodspresentedinChapter11p

3、ermitthedeterminationofcontrolcoefficientsandotherMCAparametersfromfluxestimates,evenafterlargeperturbationsinthekineticsofthenetwork.Chapters8-10providedacomprehensiveapproachtotheestimationoffluxesrequiredforthesecalculations,baseduponmetabolitebalances,reactionstoichiometries,andisotopi

4、clabels.535536MetabolicEngineeringInthischapterweturntothechallengingtaskofanalyzingfluxcontrolinmorecomplexnetworksthanthesimpleunbranchedorbranchedpathwaysdiscussedinChapter11.Wedefineacomplexmetabolicnetworkasasystemconsistingofmanyenzymaticreactionsproducinganddepletingmetabolitesandin

5、teractingwithoneanotherthroughcommonprecursors,products,oreffectors.Suchnetworksprocessexternalsubstratesthroughaseriesofreactionswhichultimatelyproduceoneormoredesirableproducts,oftenincompetitionwithunwantedbyproducts.Anexample,whichwillbeusedasacasestudythroughoutthisandthefollowingchap

6、ter,isthearomaticaminoacidbiosyntheticpathway(Fig.12.1).Withtheuseofamodelforthenetworkreactionkinetics(StephanopoulosandSimpson,1997),wewillillustratethemethodsallowingexperimentalelucidationofthecontrolstructureofthisnetwork,oranysimilarlycomplexsystem.Theobjectivesofthisandthefollowingc

7、hapteraretoprovidegeneralandsystematicmethodsfor 9definingtheintrinsicstructureofanetwork,intermsofidentifiablebranchpoints,baseduponthesystem'sstoichiometry; 9analyzingthekineticbehaviorofcomplexmetabolicnetworksintermsofMCAparameters; 9identifyingcriticalrea

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