Kinetic behavior of the general modifier mechanism of Botts and Morales with non-equilibrium binding

DOI10.1016/J.JTBI.2011.11.006MaRDI QIDQ1787093zbMATH OpenOpenAlexWikidataFDO

Authors Chen Jia, Xufeng Liu, Yuping Zhang, Minping Qian, Da-Quan Jiang

Publication date 26 September 2018

Published in Journal of Theoretical Biology (Search for Journal in Brave)

Full work available at URL https://arxiv.org/abs/1008.4501

zbMATH Keywords

effectorinhibitorNESSnet fluxswitching behavior

Mathematics Subject Classification ID

Kinetics in biochemical problems (pharmacokinetics, enzyme kinetics, etc.) (92C45)

Abstract: In this paper, we perform a complete analysis of the kinetic behavior of the general modifier mechanism of Botts and Morales in both equilibrium steady states and non-equilibrium steady states (NESS). Enlightened by the non-equilibrium theory of Markov chains, we introduce the net flux into discussion and acquire an expression of product rate in NESS, which has clear biophysical significance. Up till now, it is a general belief that being an activator or an inhibitor is an intrinsic property of the modifier. However, we reveal that this traditional point of view is based on the equilibrium assumption. A modifier may no longer be an overall activator or inhibitor when the reaction system is not in equilibrium. Based on the regulation of enzyme activity by the modifier concentration, we classify the kinetic behavior of the modifier into three categories, which are named hyperbolic behavior, bell-shaped behavior, and switching behavior, respectively. We show that the switching phenomenon, in which a modifier may convert between an activator and an inhibitor when the modifier concentration varies, occurs only in NESS. Effects of drugs on the Pgp ATPase activity, where drugs may convert from activators to inhibitors with the increase of the drug concentration, are taken as a typical example to demonstrate the occurrence of the switching phenomenon.

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Cites work

• Chemical biophysics. Quantitative analysis of cellular systems.
• Kinetic behaviour of proenzymes activation in the presence of different inhibitors for both activating and activated enzymes
• Mathematical theory of nonequilibrium steady states. On the frontier of probability and dynamical systems.

Cited in

(1)

• Simultaneous interaction of enzymes with two modifiers: reappraisal of kinetic models and new paradigms

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