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Zero-order ultrasensitivity: A study of criticality and fluctuations under the total quasi-steady state approximation in the linear noise regime
Ushasi N. Roy,
Published in Academic Press
2014
Volume: 344
   
Pages: 1 - 11
Abstract
Zero-order ultrasensitivity (ZOU) is a long known and interesting phenomenon in enzyme networks. Here, a substrate is reversibly modified by two antagonistic enzymes (a 'push-pull' system) and the fraction in modified state undergoes a sharp switching from near-zero to near-unity at a critical value of the ratio of the enzyme concentrations, under saturation conditions. ZOU and its extensions have been studied for several decades now, ever since the seminal paper of Goldbeter and Koshland (1981); however, a complete probabilistic treatment, important for the study of fluctuations in finite populations, is still lacking. In this paper, we study ZOU using a modular approach, akin to the total quasi-steady state approximation (tQSSA). This approach leads to a set of Fokker-Planck (drift-diffusion) equations for the probability distributions of the intermediate enzyme-bound complexes, as well as the modified/unmodified fractions of substrate molecules. We obtain explicit expressions for various average fractions and their fluctuations in the linear noise approximation (LNA). The emergence of a 'critical point' for the switching transition is rigorously established. New analytical results are derived for the average and variance of the fractional substrate concentration in various chemical states in the near-critical regime. For the total fraction in the modified state, the variance is shown to be a maximum near the critical point and decays algebraically away from it, similar to a second-order phase transition. The new analytical results are compared with existing ones as well as detailed numerical simulations using a Gillespie algorithm. © 2013 Elsevier Ltd.
About the journal
JournalJournal of Theoretical Biology
PublisherAcademic Press
Open AccessNo
Concepts (39)
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    CELL ENZYME
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    Algorithm
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    Computer simulation
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    Enzyme activity
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    EQUATION
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    Probability
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    Reaction kinetics
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    Stochasticity
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    Article
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    Comparative study
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    Complex formation
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    Controlled study
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    Data analysis
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    Enzyme kinetics
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    LINEAR NOISE APPROXIMATION
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    Linear system
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    Mathematical analysis
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    Mathematical computing
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    MATHEMATICAL PHENOMENA
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    Michaelis menten kinetics
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    Molecular dynamics
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    Phase transition
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    Physical phenomena
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    Priority journal
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    Process development
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    Quasi steady state approximation
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    Stochastic model
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    ZERO ORDER ULTRASENSITIVITY
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    MASTER EQUATION
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    MOLECULAR SWITCH
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    Stochastic simulation
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    VAN KAMPEN EXPANSION
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    Algorithms
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    Animals
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    Biocatalysis
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    Enzymes
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    Models, chemical
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    Multienzyme complexes
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    Stochastic processes