Application of a generalized MWC model for the mathematical simulation of metabolic pathways regulated by allosteric enzymes.
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 the way for a more generalized prediction of the behavior of bifunctional enzymes.
Najdi
Tarek S
TS
Institute for Genomics and Bioinformatics, Department of Microbiology and Molecular Genetics, College of Medicine, University of California, Irvine, Irvine, California 92697, USA. tnajdi@uci.edu
Yang
Chin-Rang
CR
Shapiro
Bruce E
BE
Hatfield
G Wesley
GW
Mjolsness
Eric D
ED
D000465:Algorithms; D000494:Allosteric Regulation / Q000502:physiology; D001224:Aspartic Acid / Q000378:metabolism*; D001225:Aspartokinase Homoserine Dehydrogenase / Q000378:metabolism*; D003198:Computer Simulation; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D008954:Models, Biological; D009097:Multienzyme Complexes / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013912:Threonine / Q000096:biosynthesis*
D029968:Escherichia coli Proteins; D009097:Multienzyme Complexes; D013912:Threonine; D001224:Aspartic Acid; D001225:Aspartokinase Homoserine Dehydrogenase