title: A model of yeast glycolysis based on a consistent kinetic characterisation of all its enzymes.
abstract: We present an experimental and computational pipeline for the generation of kinetic models of metabolism, and demonstrate its application to glycolysis in Saccharomyces cerevisiae. Starting from an approximate mathematical model, we employ a "cycle of knowledge" strategy, identifying the steps with most control over flux. Kinetic parameters of the individual isoenzymes within these steps are measured experimentally under a standardised set of conditions. Experimental strategies are applied to establish a set of in vivo concentrations for isoenzymes and metabolites. The data are integrated into a mathematical model that is used to predict a new set of metabolite concentrations and reevaluate the control properties of the system. This bottom-up modelling study reveals that control over the metabolic network most directly involved in yeast glycolysis is more widely distributed than previously thought.
authors.affiliation: Manchester Centre for Integrative Systems Biology, Manchester Institute of Biotechnology, The University of Manchester, UK.
authors.forename: Kieran
authors.initials: K
authors.lastname: Smallbone
authors.forename: Hanan L
authors.initials: HL
authors.lastname: Messiha
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Carroll
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Winder
authors.forename: Naglis
authors.initials: N
authors.lastname: Malys
authors.forename: Warwick B
authors.initials: WB
authors.lastname: Dunn
authors.forename: Ettore
authors.initials: E
authors.lastname: Murabito
authors.forename: Neil
authors.initials: N
authors.lastname: Swainston
authors.forename: Joseph O
authors.initials: JO
authors.lastname: Dada
authors.forename: Farid
authors.initials: F
authors.lastname: Khan
authors.forename: Pınar
authors.initials: P
authors.lastname: Pir
authors.forename: Evangelos
authors.initials: E
authors.lastname: Simeonidis
authors.forename: Irena
authors.initials: I
authors.lastname: Spasić
authors.forename: Jill
authors.initials: J
authors.lastname: Wishart
authors.forename: Dieter
authors.initials: D
authors.lastname: Weichart
authors.forename: Neil W
authors.initials: NW
authors.lastname: Hayes
authors.forename: Daniel
authors.initials: D
authors.lastname: Jameson
authors.forename: David S
authors.initials: DS
authors.lastname: Broomhead
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Oliver
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Gaskell
authors.forename: John E G
authors.initials: JE
authors.lastname: McCarthy
authors.forename: Norman W
authors.initials: NW
authors.lastname: Paton
authors.forename: Hans V
authors.initials: HV
authors.lastname: Westerhoff
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Kell
authors.forename: Pedro
authors.initials: P
authors.lastname: Mendes
mesh_terms: D003198:Computer Simulation; D006019:Glycolysis; D007527:Isoenzymes / Q000737:chemistry; D007700:Kinetics; D053858:Metabolic Networks and Pathways; D008954:Models, Biological; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry*; D049490:Systems Biology
chemical_list: D007527:Isoenzymes; D029701:Saccharomyces cerevisiae Proteins
keywords: Enzyme kinetic; Glycolysis; Isoenzyme; Modelling; Systems biology