作者
Kosmas Kosmidis, Vangelis Karalis, Panos Argyrakis, Panos Macheras
发表日期
2004/9/1
期刊
Biophysical journal
卷号
87
期号
3
页码范围
1498-1506
出版商
Elsevier
简介
Two different approaches were used to study the kinetics of the enzymatic reaction under heterogeneous conditions to interpret the unusual nonlinear pharmacokinetics of mibefradil. Firstly, a detailed model based on the kinetic differential equations is proposed to study the enzymatic reaction under spatial constraints and in vivo conditions. Secondly, Monte Carlo simulations of the enzyme reaction in a two-dimensional square lattice, placing special emphasis on the input and output of the substrate were applied to mimic in vivo conditions. Both the mathematical model and the Monte Carlo simulations for the enzymatic reaction reproduced the classical Michaelis-Menten (MM) kinetics in homogeneous media and unusual kinetics in fractal media. Based on these findings, a time-dependent version of the classic MM equation was developed for the rate of change of the substrate concentration in disordered media …
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