Simulating feedback and reversibility in substrate-enzyme reactions
- 330 Downloads
We extend discrete event models (DEM) of substrate-enzyme reactions to include regulatory feedback and reversible reactions. Steady state as well as transient systems are modeled and validated against ordinary differential equation (ODE) models. The approach is exemplified in a model of the first steps of glycolysis with the most common regulatory mechanisms. We find that in glycolysis, feedback and reversibility together act as a significant damper on the stochastic variations of the intermediate products as well as for the stochastic variation of the transit times. This suggests that these feedbacks have evolved to control both the overall rate of, as well as stochastic fluctuations in, glycolysis.
KeywordsDiscrete Event Search Time Stochastic Variation Discrete Event Simulation Substrate Molecule
- 8.J.J. Cazzulo, FASEB J. 6, 3153 (1993)Google Scholar
- 10.H. Chen, D.D. Yao, Fundamentals of Queueing Networks: Performance, Asymptotics, and Optimization (Springer, Verlag, 2001)Google Scholar
- 11.E. Lefeber, D. Armbruster, Aggregate modeling of manufacturing systems, in Handbook of Production Planning, edited by R. Uzsoy, P. Keskinocak, K. Kempf, Kluwer International Series in Operation Research and Management Science (Chapman Hall, 2010)Google Scholar
- 12.G.E. Briggs, J.B.S. Haldane, Biochem. J. 19, 338 (1925)Google Scholar
- 13.L. Michaelis, M. Menten, Biochemische Zeitschrift 49, 333 (1913)Google Scholar
- 18.D.A.J. van Zwieten, Modeling biological networks with discrete event models, Master’s thesis, Eindhoven University of Technology, The Netherlands, 2010Google Scholar
- 26.J.C.M. Baeten, D.A. van Beek, J.E. Rooda, Process Algebra, in Handbook of System Modeling, edited by P.A. Fishwick (Chapman Hall, Boca Ratan, 2007)Google Scholar
Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution and reproduction in any medium, provided the original author(s) and source are credited.