| Title | Kinetic behavior of the general modifier mechanism of Botts and Morales with non-equilibrium binding |
| Authors | Jia, Chen Liu, Xu-Feng Qian, Min-Ping Jiang, Da-Quan Zhang, Yu-Ping |
| Affiliation | Peking Univ, Sch Math Sci, Beijing 100871, Peoples R China. Peking Univ, Ctr Theoret Biol, Beijing 100871, Peoples R China. Beijing Int Ctr Math Res, Beijing 100871, Peoples R China. |
| Keywords | Inhibitor Effector NESS Net flux Switching behavior SUICIDE SUBSTRATE ENZYME-SYSTEMS RAPID EQUILIBRIUM P-GLYCOPROTEIN DRUG TRANSPORT STEADY-STATES INHIBITION ACTIVATION EQUATIONS SINGLE |
| Issue Date | 2012 |
| Publisher | 理论生物学杂志 |
| Citation | JOURNAL OF THEORETICAL BIOLOGY.2012,296,13-20. |
| 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 the rate of product formation 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. (C) 2011 Elsevier Ltd. All rights reserved. |
| URI | http://hdl.handle.net/20.500.11897/157238 |
| ISSN | 0022-5193 |
| DOI | 10.1016/j.jtbi.2011.11.006 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 数学科学学院 |
