A proof of bistability for the dual futile cycle

DOI10.1016/J.NONRWA.2015.02.004zbMATH Open1331.34089arXiv1404.0394OpenAlexW2963135937MaRDI QIDQ892271FDOQ892271

Alan D. Rendall, Juliette Hell

Publication date: 18 November 2015

Published in: Nonlinear Analysis. Real World Applications (Search for Journal in Brave)

Abstract: The multiple futile cycle is an important building block in networks of chemical reactions arising in molecular biology. A typical process which it describes is the addition of n phosphate groups to a protein. It can be modelled by a system of ordinary differential equations depending on parameters. The special case n = 2 is called the dual futile cycle. The main result of this paper is a proof that there are parameter values for which the system of ODE describing the dual futile cycle has two distinct stable stationary solutions. The proof is based on bifurcation theory and geometric singular perturbation theory. An important entity built of three coupled multiple futile cycles is the MAPK cascade. It is explained how the ideas used to prove bistability for the dual futile cycle might help to prove the existence of periodic solutions for the MAPK cascade.

Full work available at URL: https://arxiv.org/abs/1404.0394

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zbMATH Keywords

bistabilitygeometric singular perturbation theorycusp bifurcationMAPkinase cascademultiple futile cycle

Mathematics Subject Classification ID

Qualitative investigation and simulation of ordinary differential equation models (34C60) Topological structure of integral curves, singular points, limit cycles of ordinary differential equations (34C05) Bifurcation theory for ordinary differential equations (34C23) Singular perturbations for ordinary differential equations (34E15) Cell biology (92C37) Kinetics in biochemical problems (pharmacokinetics, enzyme kinetics, etc.) (92C45)

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Cited In (16)

• A global convergence result for processive multisite phosphorylation systems
• Stability analysis of the Michaelis-Menten approximation of a mixed mechanism of a phosphorylation system
• In distributive phosphorylation catalytic constants enable non-trivial dynamics
• Parameter regions that give rise to \(2\lfloor \frac{n}{2} \rfloor +1\) positive steady states in the \(n\)-site phosphorylation system
• Structural Conditions for Saddle-Node Bifurcations in Chemical Reaction Networks
• An all-encompassing global convergence result for processive multisite phosphorylation systems
• The kinetic space of multistationarity in dual phosphorylation
• On the existence of Hopf bifurcations in the sequential and distributive double phosphorylation cycle
• Stability of stationary solutions in models of the Calvin cycle
• Algebra and Geometry in the Study of Enzymatic Cascades
• Sustained oscillations in the MAP kinase cascade
• Addition of flow reactions preserving multistationarity and bistability
• Emergence of oscillations in a mixed-mechanism phosphorylation system
• Symbolic Proof of Bistability in Reaction Networks
• Precluding oscillations in Michaelis-Menten approximations of dual-site phosphorylation systems
• A proof of unlimited multistability for phosphorylation cycles

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