Scaling in Singular Perturbation Problems: Blowing Up a Relaxation Oscillator

A detailed geometric analysis of the Goldbeter–Lefever model of glycolytic oscillations is given. In suitably scaled variables the governing equations are a planar system of ordinary differential equations depending singularly on two small parameters $\varepsilon$ and $\delta$. In [L. Segel and A. Goldbeter, J. Math. Biol., 32 (1994), pp. 147–160] it was argued that a limit cycle of relaxation type exists for $\varepsilon\ll\delta\ll1$. The existence of this limit cycle is proved by analyzing the problem in the spirit of geometric singular perturbation theory. The degeneracies of the limiting problem corresponding to $(\varepsilon,\delta)=(0,0)$ are resolved by a novel variant of the blow-up method. It is shown that repeated blow-ups lead to a clear geometric picture of this fairly complicated two-parameter multiscale problem.

[1]  Freddy Dumortier,et al.  Canard Cycles and Center Manifolds , 1996 .

[2]  Lee A. Segel,et al.  Scaling in biochemical kinetics: dissection of a relaxation oscillator , 1994 .

[3]  Peter Szmolyan,et al.  Geometric Singular Perturbation Analysis of the Yamada Model , 2005, SIAM J. Appl. Dyn. Syst..

[4]  Britton Chance,et al.  Waveform generation by enzymatic oscillators , 1967, IEEE Spectrum.

[5]  Peter Szmolyan,et al.  Relaxation oscillations in R3 , 2004 .

[6]  Peter Szmolyan,et al.  Asymptotic expansions using blow-up , 2005 .

[7]  J. Grasman Asymptotic Methods for Relaxation Oscillations and Applications , 1987 .

[8]  A. Goldbeter,et al.  Biochemical Oscillations And Cellular Rhythms: Contents , 1996 .

[9]  N. Berman,et al.  Oscillations of lactate released from islets of Langerhans: evidence for oscillatory glycolysis in beta-cells. , 1992, The American journal of physiology.

[10]  E. Sel'kov,et al.  Self-oscillations in glycolysis. 1. A simple kinetic model. , 1968, European journal of biochemistry.

[11]  B Hess,et al.  The glycolytic oscillator. , 1979, The Journal of experimental biology.

[12]  K. Ibsen,et al.  Oscillations of nucleotides and glycolytic intermediates in aerobic suspensions of Ehrlich ascites tumor cells. , 1967, Biochimica et biophysica acta.

[13]  Peter Szmolyan,et al.  Geometric singular perturbation analysis of an autocatalator model , 2009 .

[14]  P. Holmes,et al.  Nonlinear Oscillations, Dynamical Systems, and Bifurcations of Vector Fields , 1983, Applied Mathematical Sciences.

[15]  Christopher Jones,et al.  Geometric singular perturbation theory , 1995 .

[16]  P. Smolen,et al.  A model for glycolytic oscillations based on skeletal muscle phosphofructokinase kinetics. , 1995, Journal of theoretical biology.

[17]  N. K. Rozov,et al.  Differential Equations with Small Parameters and Relaxation Oscillations , 1980 .

[18]  Stephen Schecter,et al.  Persistence of Rarefactions under Dafermos Regularization: Blow-Up and an Exchange Lemma for Gain-of-Stability Turning Points , 2009, SIAM J. Appl. Dyn. Syst..

[19]  J. Cole,et al.  Multiple Scale and Singular Perturbation Methods , 1996 .

[20]  A Goldbeter,et al.  Dissipative structures for an allosteric model. Application to glycolytic oscillations. , 1972, Biophysical journal.

[21]  Nancy Kopell,et al.  Mixed-Mode Oscillations in Three Time-Scale Systems: A Prototypical Example , 2008, SIAM J. Appl. Dyn. Syst..

[22]  R. Bertram,et al.  Metabolic and electrical oscillations: partners in controlling pulsatile insulin secretion. , 2007, American journal of physiology. Endocrinology and metabolism.

[23]  Freddy Dumortier,et al.  Canard solutions at non-generic turning points , 2005 .

[24]  Freddy Dumortier,et al.  Multiple Canard Cycles in Generalized Liénard Equations , 2001 .

[25]  E. Marbán,et al.  Oscillations of membrane current and excitability driven by metabolic oscillations in heart cells. , 1994, Science.

[26]  A. Macgillivray,et al.  AN INTRODUCTION TO SINGULAR PERTURBATIONS , 2000 .

[27]  P. Szmolyana,et al.  Relaxation oscillations in R 3 , 2004 .

[28]  P. Szmolyan,et al.  Canards in R3 , 2001 .

[29]  Peter Szmolyan,et al.  Extending Geometric Singular Perturbation Theory to Nonhyperbolic Points - Fold and Canard Points in Two Dimensions , 2001, SIAM J. Math. Anal..

[30]  M. Krupa,et al.  Relaxation Oscillation and Canard Explosion , 2001 .

[31]  R. Frenkel,et al.  Control of reduced diphosphopyridine nucleotide oscillations in beef heart extracts. I. Effects of modifiers of phosphofructokinase activity. , 1968, Archives of biochemistry and biophysics.

[32]  J. Higgins,et al.  A CHEMICAL MECHANISM FOR OSCILLATION OF GLYCOLYTIC INTERMEDIATES IN YEAST CELLS. , 1964, Proceedings of the National Academy of Sciences of the United States of America.

[33]  Nikola Popović,et al.  The critical wave speed for the Fisher–Kolmogorov–Petrowskii–Piscounov equation with cut-off , 2007 .

[34]  Nikola Popović,et al.  A geometric analysis of the Lagerstrom model problem , 2004 .