Metabolic network structure determines key aspects of functionality and regulation

Jörg Stelling (), Steffen Klamt, Katja Bettenbrock, Stefan Schuster and Ernst Dieter Gilles
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Jörg Stelling: Max Planck Institute for Dynamics of Complex Technical Systems
Steffen Klamt: Max Planck Institute for Dynamics of Complex Technical Systems
Katja Bettenbrock: Max Planck Institute for Dynamics of Complex Technical Systems
Stefan Schuster: Max Delbrück Center for Molecular Medicine
Ernst Dieter Gilles: Max Planck Institute for Dynamics of Complex Technical Systems

Nature, 2002, vol. 420, issue 6912, 190-193

Abstract: Abstract The relationship between structure, function and regulation in complex cellular networks is a still largely open question1,2,3. Systems biology aims to explain this relationship by combining experimental and theoretical approaches4. Current theories have various strengths and shortcomings in providing an integrated, predictive description of cellular networks. Specifically, dynamic mathematical modelling of large-scale networks meets difficulties because the necessary mechanistic detail and kinetic parameters are rarely available. In contrast, structure-oriented analyses only require network topology, which is well known in many cases. Previous approaches of this type focus on network robustness5 or metabolic phenotype2,6, but do not give predictions on cellular regulation. Here, we devise a theoretical method for simultaneously predicting key aspects of network functionality, robustness and gene regulation from network structure alone. This is achieved by determining and analysing the non-decomposable pathways able to operate coherently at steady state (elementary flux modes). We use the example of Escherichia coli central metabolism to illustrate the method.

Date: 2002
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DOI: 10.1038/nature01166

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