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A model of yeast glycolysis based on a consistent kinetic characterisation of all its enzymes
Author(s) -
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
Publication year - 2013
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2013.06.043
Subject(s) - yeast , glycolysis , enzyme , biochemistry , chemistry , kinetic energy , computational biology , biology , physics , quantum mechanics
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.