title: Application of a generalized MWC model for the mathematical simulation of metabolic pathways regulated by allosteric enzymes.
abstract: In our effort to elucidate the systems biology of the model organism, Escherichia coli, we have developed a mathematical model that simulates the allosteric regulation for threonine biosynthesis pathway starting from aspartate. To achieve this goal, we used kMech, a Cellerator language extension that describes enzyme mechanisms for the mathematical modeling of metabolic pathways. These mechanisms are converted by Cellerator into ordinary differential equations (ODEs) solvable by Mathematica. In this paper, we describe a more flexible model in Cellerator, which generalizes the Monod, Wyman, Changeux (MWC) model for enzyme allosteric regulation to allow for multiple substrate, activator and inhibitor binding sites. Furthermore, we have developed a model that describes the behavior of the bifunctional allosteric enzyme aspartate Kinase I-Homoserine Dehydrogenase I (AKI-HDHI). This model predicts the partition of enzyme activities in the steady state which paves a way for a more generalized prediction of the behavior of bifunctional enzymes.
authors.affiliation: Institute for Genomics and Bioinformatics, University of California at Irvine, Irvine, CA 92697, USA.
authors.forename: Tarek S
authors.initials: TS
authors.lastname: Najdi
authors.forename: Chin-Rang
authors.initials: CR
authors.lastname: Yang
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Shapiro
authors.forename: G Wesley
authors.initials: GW
authors.lastname: Hatfield
authors.forename: Eric D
authors.initials: ED
authors.lastname: Mjolsness
mesh_terms: D000465:Algorithms; D000495:Allosteric Site / Q000502:physiology; D003198:Computer Simulation; D004798:Enzymes / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D008954:Models, Biological; D009097:Multienzyme Complexes / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D004798:Enzymes; D029968:Escherichia coli Proteins; D009097:Multienzyme Complexes