Application of a generalized MWC model for the mathematical simulation of metabolic pathways regulated by allosteric enzymes
Application of a generalized MWC model for the mathematical simulation of metabolic pathways regulated by allosteric enzymes
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DOI：
10.1142/s0219720006001862
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发表时间：
2006-04-01
影响因子：
1
通讯作者：
Mjolsness, Eric D.
中科院分区：
文献类型：
--
作者：
Najdi, Tarek S.;Yang, Chin-Rang;Mjolsness, Eric D.
为了阐明模式生物大肠杆菌的系统生物学，我们建立了一个数学模型，模拟了从天冬氨酸开始的苏氨酸生物合成途径的变弹性调节。为了实现这一目标，我们使用了kMech，这是一种Cellerator语言扩展，用于描述代谢途径数学建模的酶机制。这些机制由Cellerator转换成可由Mathematica （TM）求解的常微分方程（ode）。在本文中，我们在Cellerator中描述了一个更灵活的模型，它将Monod， Wyman, Changeux （MWC）模型推广到酶变构调节，以允许多个底物，激活剂和抑制剂结合位点。此外，我们开发了一个模型来描述双功能变构酶天冬氨酸激酶1-高丝氨酸脱氢酶I （AKI-HDHI）的行为。该模型预测了稳定状态下酶活性的分配，为更广泛地预测双功能酶的行为铺平了道路。
In our effort to elucidate the systems biology of the model organism, Escherichia coli, we have developed a mathematical model that simulates the allosteric regulation for threonine biosynthesis pathway starting from aspartate. To achieve this goal, we used kMech, a Cellerator language extension that describes enzyme mechanisms for the mathematical modeling of metabolic pathways. These mechanisms are converted by Cellerator into ordinary differential equations (ODEs) solvable by Mathematica (TM). In this paper, we describe a more flexible model in Cellerator, which generalizes the Monod, Wyman, Changeux (MWC) model for enzyme allosteric regulation to allow for multiple substrate, activator and inhibitor binding sites. Furthermore, we have developed a model that describes the behavior of the bifunctional allosteric enzyme aspartate kinase 1-homoserine dehydrogenase I (AKI-HDHI). This model predicts the partition of enzyme activities in the steady state which paves the way for a more generalized prediction of the behavior of bifunctional enzymes.