TY - JOUR
T1 - Non-linear reduction for kinetic models of metabolic reaction networks
AU - Gerdtzen, Ziomara P.
AU - Daoutidis, Prodromos
AU - Hu, Wei Shou
PY - 2004/4
Y1 - 2004/4
N2 - Kinetic models of metabolic networks are essential for predicting and optimizing the transient behavior of cells in culture. However, such models are inherently high dimensional and stiff due to the large number of species and reactions involved and to kinetic rate constants of widely different orders of magnitude. In this paper we address the problem of deriving non-stiff, reduced-order non-linear models of the dominant dynamics of metabolic networks with fast and slow reactions. We present a method, based on singular perturbation analysis, which allows the systematic identification of quasi-steady-state conditions for the fast reactions, and the derivation of explicit non-linear models of the slow dynamics independent of the fast reaction rate expressions. The method is successfully applied to detailed models of metabolism in human erythrocytes and Saccharomyces cerevisiae.
AB - Kinetic models of metabolic networks are essential for predicting and optimizing the transient behavior of cells in culture. However, such models are inherently high dimensional and stiff due to the large number of species and reactions involved and to kinetic rate constants of widely different orders of magnitude. In this paper we address the problem of deriving non-stiff, reduced-order non-linear models of the dominant dynamics of metabolic networks with fast and slow reactions. We present a method, based on singular perturbation analysis, which allows the systematic identification of quasi-steady-state conditions for the fast reactions, and the derivation of explicit non-linear models of the slow dynamics independent of the fast reaction rate expressions. The method is successfully applied to detailed models of metabolism in human erythrocytes and Saccharomyces cerevisiae.
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U2 - 10.1016/j.ymben.2003.11.003
DO - 10.1016/j.ymben.2003.11.003
M3 - Article
C2 - 15113567
AN - SCOPUS:2342567053
VL - 6
SP - 140
EP - 154
JO - Metabolic Engineering
JF - Metabolic Engineering
SN - 1096-7176
IS - 2
ER -