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1、CHAPTER3ComprehensiveModelsforCellularReactionsInthepreviouschapter,wereviewedthemainmetabolicpathwaysbywhichcarbon-energysourcesarecatabolizedfortheproductionoffreeenergyandcarbonskeletonsneededformetabolitesynthesisandcellgrowth.Tocompletethepictureo
2、fintermediarymetabolism,thecomplexpathwaysofChapter2needtobecomplementedwithinformationaboutthestoi-chiometry,kinetics,andthermodynamicsoftheindividualreactions.Ther-modynamics,asubjectdealingprimarilywithissuesofreactionandpathwayfeasibility,willbedis
3、cussedatlengthinChapter14.Informationonreactionkinetics,especiallyunderinvivoconditions,isparticularlyhardtocomeby,yetsuchinformationisnecessaryforunderstandingthemechanismsofmetabolicfluxcontrol,acentralissueofmetabolicengineeringand,indeed,ofthistext
4、book.Stoichiometryisreadilyavailableforindividualreactionsfromextensivestudiesconductedonintermediarymetabolism.Extensionofthesereactionstoichiometriestometabolicpathwaysprovidesthebasisforsettingupenergyandmaterialbalances,aswellasaccountingforinterac
5、-8182MetabolicEngineeringtionsamongcoupledreactionsandpathways.Pathwaystoichiometryim-posesconstraintsthatmustbesatisfiedbycellcultivationmeasurements,raisingissuesofdataconsistencydiscussedinthenextchapter.Inthischapterwereviewmethodsbywhichthesumtota
6、lofcellularreactionsarelumpedtogethertoprovidecomprehensivemodelsofcellularmetabolism.Clearly,onlyafewofallpossiblecellularreactionsareconsid-eredexplicitly,asmanyofthemarenotevenknownortheirinclusionwouldleadtoanoverwhelminglylargesystem.Atthesametime
7、itisnotcleartowhatextentthefidelityorusefulnessofcellularmodelsmightbeenhancedbyincreasingthedetailofmetabolicrepresentation.Astherearemanywaysinwhichreactionlumpingcanbeexecuted,itisimportantthatsuchlumpingbecarriedoutrationallyandinaconsistentmanner.
8、Wethereforeprovideaframeworkfordevelopingthestoichiometryofcellularmodels,whichisalsoapplicabletotheanalysisofverylargereactionnetworks.3.1.STOICHIOMETRYOFCELLULARREACTIONSTheoverallresultofthetotalityofcellularreactionsistheconversiono
