A model of yeast glycolysis based on a consistent kinetic characterisation of all its enzymes

Research output: Contribution to journalArticle

Authors

  • Kieran Smallbone
  • Hanan L Messiha
  • Kathleen M Carroll
  • Naglis Malys
  • Ettore Murabito
  • Neil Swainston
  • Joseph O Dada
  • Farid Khan
  • Pınar Pir
  • Evangelos Simeonidis
  • Irena Spasić
  • Jill Wishart
  • Dieter Weichart
  • Neil W Hayes
  • Daniel Jameson
  • David S Broomhead
  • Stephen G Oliver
  • Simon J Gaskell
  • John E G McCarthy
  • Norman W Paton
  • Hans V Westerhoff
  • Douglas B Kell
  • Pedro Mendes

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.

Details

Original languageEnglish
Pages (from-to)2832-41
Number of pages10
JournalFEBS Letters
Volume587
Issue number17
Publication statusPublished - 2 Sep 2013

Keywords

  • Computer Simulation, Glycolysis, Isoenzymes, Kinetics, Metabolic Networks and Pathways, Models, Biological, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Systems Biology