Attractor Metabolic Networks.docVIP

AttractorMetabolicNetworks IldefonsoM.DelaFuente1,2,3*,JesusM.Cortes1,4,DavidA.Pelta5,JuanVeguillas1 1QuantitativeBiomedicineUnit,BioCrucesHealthResearchInstitute,Barakaldo,BasqueCountry,Spain,2InstituteofParasitologyandBiomedicine‘‘Lo′pezNeyra’’,CSIC, Granada, Spain, 3Department of Mathematics, University of the Basque Country, EHU-UPV, Leioa, Basque Country, Spain, 4Ikerbasque: The Basque Foundation for Science,Bilbao,BasqueCountry,Spain,5DepartmentofComputerScienceandArtificialIntelligence,UniversityofGranada,Granada,Spain Abstract Background:Theexperimentalobservationsandnumericalstudieswithdissipativemetabolicnetworkshaveshownthat cellularenzymaticactivityself-organizesspontaneouslyleadingtotheemergenceofaSystemicMetabolicStructureinthe cell,characterizedbyasetofdifferentenzymaticreactionsalwayslockedintoactivestates(metaboliccore)whiletherestof the catalytic processes are only intermittently active. This global metabolic structure was verified for Escherichia coli, Helicobacter pylori and Saccharomyces cerevisiae, and it seems to be a common key feature to all cellular organisms. In concordancewiththeseobservations,thecellcanbeconsideredacomplexmetabolicnetworkwhichmainlyintegratesa large ensemble of self-organized multienzymatic complexes interconnected by substrate fluxes and regulatory signals, wheremultipleautonomousoscillatoryandquasi-stationarycatalyticpatternssimultaneouslyemerge.Thenetworkadjusts theinternalmetabolicactivitiestotheexternalchangebymeansoffluxplasticityandstructuralplasticity. Methodology/PrincipalFindings:Inordertoresearchthesystemicmechanismsinvolvedintheregulationofthecellular enzymaticactivitywehavestudieddifferentcatalyticactivitiesofadissipativemetabolicnetworkunderdifferentexternal stimuli.Theemergentbiochemicaldatahavebeenanalysedusingstatisticalmechanictools,studyingsomemacroscopic properties such as the global information and the energy of the system. We have also obtained an equivalent Hopfield network using a Boltzmann mach