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

Smallbone, Kieran and Messiha, Hanan L. and Carroll, Kathleen M. and Winder, Catherine L. and Malys, Naglis and Dunn, Warwick B. and Murabito, Ettore and Swainston, Neil and Dada, Joseph O. and Khan, Farid and Pir, Pınar and Simeonidis, Evangelos and Spasić, Irena and Wishart, Jill and Weichart, Dieter and Hayes, Neil W. and Jameson, Daniel and Broomhead, David S. and Oliver, Stephen G. and Gaskell, Simon J. and McCarthy, John E.G. and Paton, Norman W. and Westerhoff, Hans V. and Kell, Douglas B. and Pendes, Pedro (2013) A model of yeast glycolysis based on a consistent kinetic characterisation of all its enzymes. FEBS Letters, 587 (17). pp. 2832-2841.

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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.

Item Type:	Article
Uncontrolled Keywords:	Glycolysis; Systems biology; Enzyme kinetic; Isoenzyme; Modelling
Subjects:	MSC 2010, the AMS's Mathematics Subject Classification > 92 Biology and other natural sciences
Depositing User:	Dr Kieran Smallbone
Date Deposited:	12 Jul 2015
Last Modified:	20 Oct 2017 14:13
URI:	https://eprints.maths.manchester.ac.uk/id/eprint/2338

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