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Theor Biol Med Model. 2006 Dec 15;3:41.

Bringing metabolic networks to life: convenience rate law and thermodynamic constraints.

Author information

1
Computational Systems Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany. lieberme@molgen.mpg.de

Abstract

BACKGROUND:

Translating a known metabolic network into a dynamic model requires rate laws for all chemical reactions. The mathematical expressions depend on the underlying enzymatic mechanism; they can become quite involved and may contain a large number of parameters. Rate laws and enzyme parameters are still unknown for most enzymes.

RESULTS:

We introduce a simple and general rate law called "convenience kinetics". It can be derived from a simple random-order enzyme mechanism. Thermodynamic laws can impose dependencies on the kinetic parameters. Hence, to facilitate model fitting and parameter optimisation for large networks, we introduce thermodynamically independent system parameters: their values can be varied independently, without violating thermodynamical constraints. We achieve this by expressing the equilibrium constants either by Gibbs free energies of formation or by a set of independent equilibrium constants. The remaining system parameters are mean turnover rates, generalised Michaelis-Menten constants, and constants for inhibition and activation. All parameters correspond to molecular energies, for instance, binding energies between reactants and enzyme.

CONCLUSION:

Convenience kinetics can be used to translate a biochemical network--manually or automatically--into a dynamical model with plausible biological properties. It implements enzyme saturation and regulation by activators and inhibitors, covers all possible reaction stoichiometries, and can be specified by a small number of parameters. Its mathematical form makes it especially suitable for parameter estimation and optimisation. Parameter estimates can be easily computed from a least-squares fit to Michaelis-Menten values, turnover rates, equilibrium constants, and other quantities that are routinely measured in enzyme assays and stored in kinetic databases.

PMID:
17173669
PMCID:
PMC1781438
DOI:
10.1186/1742-4682-3-41
[Indexed for MEDLINE]
Free PMC Article

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