Title A model of yeast glycolysis based on a consistent kinetic characterisation of all its enzymes /
Authors Smallbone, Kieran ; Messiha, Hanan L ; Carroll, Kathleen M ; Winder, Catherine L ; Malys, Naglis ; Dunn, Warwick B ; Murabito, Ettore ; Swainston, Neil ; Dada, Joseph O ; Khan, Farid ; Pir, Pınar ; Simeonidis, Evangelos ; Spasić, Irena ; Wishart, Jill ; Weichart, Dieter ; Hayes, Neil W ; Jameson, Daniel ; Broomhead, David S ; Oliver, Stephen G ; Gaskell, Simon J ; McCarthy, John E G ; Paton, Norman W ; Westerhoff, Hans V ; Kell, Douglas B ; Mendes, Pedro
DOI 10.1016/j.febslet.2013.06.043
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Is Part of FEBS letters.. Oxford : FEBS press; John Wiley & Sons. 2013, vol. 587, iss. 17, p. 2832-2841.. ISSN 0014-5793. eISSN 1873-3468
Keywords [eng] Enzyme kinetic ; Glycolysis ; Isoenzyme ; Modelling ; Systems biology
Abstract [eng] 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.
Published Oxford : FEBS press; John Wiley & Sons
Type Journal article
Language English
Publication date 2013
CC license CC license description