PMID:15657047
| Citation |
Yang, CR, Shapiro, BE, Hung, SP, Mjolsness, ED and Hatfield, GW (2005) A mathematical model for the branched chain amino acid biosynthetic pathways of Escherichia coli K12. J. Biol. Chem. 280:11224-32 |
|---|---|
| Abstract |
As a first step toward the elucidation of the systems biology of the model organism Escherichia coli, it was our goal to mathematically model a metabolic system of intermediate complexity, namely the well studied end product-regulated pathways for the biosynthesis of the branched chain amino acids L-isoleucine, L-valine, and L-leucine. This has been accomplished with the use of kMech (Yang, C.-R., Shapiro, B. E., Mjolsness, E. D., and Hatfield, G. W. (2005) Bioinformatics 21, in press), a Cellerator (Shapiro, B. E., Levchenko, A., Meyerowitz, E. M., Wold, B. J., and Mjolsness, E. D. (2003) Bioinformatics 19, 677-678) language extension that describes a suite of enzyme reaction mechanisms. Each enzyme mechanism is parsed by kMech into a set of fundamental association-dissociation reactions that are translated by Cellerator into ordinary differential equations. These ordinary differential equations are numerically solved by Mathematica. Any metabolic pathway can be simulated by stringing together appropriate kMech models and providing the physical and kinetic parameters for each enzyme in the pathway. Writing differential equations is not required. The mathematical model of branched chain amino acid biosynthesis in E. coli K12 presented here incorporates all of the forward and reverse enzyme reactions and regulatory circuits of the branched chain amino acid biosynthetic pathways, including single and multiple substrate (Ping Pong and Bi Bi) enzyme kinetic reactions, feedback inhibition (allosteric, competitive, and non-competitive) mechanisms, the channeling of metabolic flow through isozymes, the channeling of metabolic flow via transamination reactions, and active transport mechanisms. This model simulates the results of experimental measurements. |
| Links |
PubMed Online version:10.1074/jbc.M411471200 |
| Keywords |
Acetolactate Synthase/physiology; Allosteric Regulation; Amino Acids, Branched-Chain/biosynthesis; Escherichia coli K12/genetics; Escherichia coli K12/metabolism; Isoenzymes/physiology; Isoleucine/biosynthesis; Mathematics; Models, Theoretical; Threonine Dehydratase/physiology; Valine/pharmacology |
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