In recent years, constrained optimization - usually referred to as flux-balance analysis (FBA) - has become a widely applied method for the computation of stationary fluxes in large-scale metabolic networks. The striking advantage of FBA - compared to kinetic modeling - is that it basically requires only knowledge of the stoichiometry of the network.
On the other hand, results of FBA are to a large degree hypothetical because the method relies on plausible but hardly provable optimality principles that are thought to govern metabolic flux distributions.
There are two directions in our efforts for more realistic flux distributions. One is the improvement of the optimality criterion (also called scoring function) and the introduction of meaningful and effective side-constraints that restrict the solution space in FBA.
The basis of the former is flux minimization principle [1,2], generalized in [3].
One of the most promising approaches of the latter is the inclusion of a constraint relating the net direction of a reaction flux to the sign of Gibb's free energy [4].
Researchers
Dr. Andreas HoppeProf. Hermann-Georg Holzhütter
Sabrina Hoffmann
References
[1] Holzhütter HG. (2004) The principle of flux minimization and its application to estimate stationary fluxes in metabolic networks. Eur. J. Biochem., 271(14):2905-22. [PubMed]
[2] Holzhütter S, Holzhütter HG. (2004) Computational design of reduced metabolic networks. Chembiochem., 5(10):1401-22. [PubMed]
[3] Holzhütter HG. (2006) The generalized flux-minimization method and its application to metabolic networks affected by enzyme deficiencies Biosystems., 83(2-3):98-107. [PubMed]
[4] Hoppe A, Hoffmann S, Holzhütter HG. (2007) Including metabolite concentrations into flux-balance analysis: Thermodynamic realizability as a constraint on flux distributions in metabolic networks BMC Syst. Biol., 1(1): 23. [pdf, journal, PubMed]