A multi-time-scale analysis of chemical reaction networks: I. Deterministic systems

We consider deterministic descriptions of reaction networks in which different reactions occur on at least two distinct time scales. We show that when a certain Jacobian is nonsingular there is a coordinate system in which the evolution equations for slow and fast variables are separated, and we obtain the appropriate initial conditions for the transformed system. We also discuss topological properties which guarantee that the nonsingularity condition is satisfied, and show that in the new coordinate frame the evolution of the slow variables on the slow time scale is independent of the fast variables to lowest order in a small parameter. Several examples that illustrate the numerical accuracy of the reduction are presented, and an extension of the reduction method to three or more time scale networks is discussed.

[1]  J. Bowen,et al.  Singular perturbation refinement to quasi-steady state approximation in chemical kinetics , 1963 .

[2]  Simon J. Fraser,et al.  The steady state and equilibrium approximations: A geometrical picture , 1988 .

[3]  J. Rawlings,et al.  Approximate simulation of coupled fast and slow reactions for stochastic chemical kinetics , 2002 .

[4]  S. H. Lam,et al.  Using CSP to Understand Complex Chemical Kinetics ∗ , 1992 .

[5]  H. M. Tsuchiya,et al.  On the mathematical status of the pseudo-steady state hypothesis of biochemical kinetics☆ , 1967 .

[6]  R. Aris Prolegomena to the rational analysis of systems of chemical reactions , 1965 .

[7]  A. Gibbons Algorithmic Graph Theory , 1985 .

[8]  Ulrich Maas,et al.  Simplifying chemical kinetics: Intrinsic low-dimensional manifolds in composition space , 1992 .

[9]  H. Othmer A GRAPH-THEORETIC ANALYSIS OF CHEMICAL REACTION NETWORKS I. Invariants, Network Equivalence and Nonexistence of Various Types of Steady States ∗ , 1981 .

[10]  G. B. Kistiakowsky,et al.  On the Mechanism of the Inhibition of Urease , 1953 .

[11]  S. H. Lam,et al.  Using CSP to Understand Complex Chemical Kinetics , 1993 .

[12]  S. Lam,et al.  The CSP method for simplifying kinetics , 1994 .

[13]  D J Park,et al.  The hierarchical structure of metabolic networks and the construction of efficient metabolic simulators. , 1974, Journal of theoretical biology.

[14]  H. Othmer The Interaction of Structure and Dynamics in Chemical Reaction Networks , 1981 .

[15]  Lee A. Segel,et al.  Mathematics applied to deterministic problems in the natural sciences , 1974, Classics in applied mathematics.

[16]  E. L. King,et al.  A Schematic Method of Deriving the Rate Laws for Enzyme-Catalyzed Reactions , 1956 .

[17]  H. Kijima,et al.  'Steady/equilibrium approximation' in relaxation and fluctuation. I. Procedure to simplify first-order reaction. , 1982, Biophysical chemistry.

[18]  H. Kijima,et al.  'Steady/equilibrium approximation' in relaxation and fluctuation. II. Mathematical theory of approximations in first-order reaction. , 1983, Biophysical chemistry.

[19]  Marc R. Roussel,et al.  On the geometry of transient relaxation , 1991 .

[20]  L. You,et al.  Stochastic vs. deterministic modeling of intracellular viral kinetics. , 2002, Journal of theoretical biology.

[21]  Hans G. Kaper,et al.  Analysis of the Computational Singular Perturbation Reduction Method for Chemical Kinetics , 2004, J. Nonlinear Sci..

[22]  L. A. Segel,et al.  The Quasi-Steady-State Assumption: A Case Study in Perturbation , 1989, SIAM Rev..

[23]  F. Horn Necessary and sufficient conditions for complex balancing in chemical kinetics , 1972 .

[24]  H. Othmer,et al.  A stochastic analysis of first-order reaction networks , 2005, Bulletin of mathematical biology.

[25]  Marc R. Roussel,et al.  Invariant manifold methods for metabolic model reduction. , 2001, Chaos.

[26]  Iliya V. Karlin,et al.  Method of invariant manifold for chemical kinetics , 2003 .

[27]  Matthias Stiefenhofer Quasi-steady-state approximation for chemical reaction networks , 1998 .

[28]  H. Othmer,et al.  The effects of cell density and metabolite flux on cellular dynamics , 1978, Journal of mathematical biology.

[29]  Willi Jäger,et al.  Modelling of Chemical Reaction Systems , 1981 .

[30]  I. Prigogine,et al.  Symmetry Breaking Instabilities in Dissipative Systems. II , 1968 .

[31]  Hans G. Othmer,et al.  Nonuniqueness of equilibria in closed reacting systems , 1976 .

[32]  Mauro Valorani,et al.  An efficient iterative algorithm for the approximation of the fast and slow dynamics of stiff systems , 2006, J. Comput. Phys..

[33]  Marc R. Roussel,et al.  Geometry of the steady-state approximation: Perturbation and accelerated convergence methods , 1990 .

[34]  R. Jackson,et al.  General mass action kinetics , 1972 .

[35]  T. B. Boffey,et al.  Applied Graph Theory , 1973 .

[36]  R. H. Snow,et al.  A Chemical Kinetics Computer Program for Homogeneous and Free-Radical Systems of Reactions , 1966 .

[37]  V. Becerra,et al.  Optimal control of nonlinear differential algebraic equation systems , 2000, Proceedings of the 39th IEEE Conference on Decision and Control (Cat. No.00CH37187).

[38]  Hans G. Kaper,et al.  Fast and Slow Dynamics for the Computational Singular Perturbation Method , 2004, Multiscale Model. Simul..

[39]  P. Daoutidis,et al.  Control of nonlinear differential algebraic equation systems , 1999 .

[40]  Habib N. Najm,et al.  An automatic procedure for the simplification of chemical kinetic mechanisms based on CSP , 2006 .