Modular rate laws for enzymatic reactions: thermodynamics, elasticities and implementation
Modular rate laws for enzymatic reactions: thermodynamics, elasticities and implementation
复制标题
DOI：
10.1093/bioinformatics/btq141
复制
发表时间：
2010-06-15
期刊：
影响因子：
5.8
通讯作者：
Klipp, Edda
中科院分区：
文献类型：
--
作者：
Liebermeister, Wolfram;Uhlendorf, Jannis;Klipp, Edda
动机：标准速率定律是将代谢网络系统地转化为动力学模型的关键前提。他们应该提供简单、通用和生化上合理的反应速度和反应弹性公式。同时，他们需要尊重动力学常数与代谢通量和浓度之间的热力学关系。结果：我们提出了一系列具有任意化学计量和各种类型调节的反应的可逆速率定律，包括质量作用、米氏和单-单可逆希尔动力学作为特例。通过对这些速率定律进行热力学安全参数化，通过模型拟合、采样或优化获得的参数集可保证产生一致的化学平衡状态。使用饱和值重新公式化产生简单的速率和弹性公式，可以轻松地将其调整为给定的固定通量分布。此外，该公式强调了化学势差作为热力学驱动力的作用。我们将模块化速率定律与热力学动力学建模形式进行比较，并讨论了一种简化的速率定律，其中反应速率直接取决于反应亲和力。为了自动处理模块化速率定律，我们提出了系统生物学标记语言的标准语法和语义注释。
Motivation: Standard rate laws are a key requisite for systematically turning metabolic networks into kinetic models. They should provide simple, general and biochemically plausible formulae for reaction velocities and reaction elasticities. At the same time, they need to respect thermodynamic relations between the kinetic constants and the metabolic fluxes and concentrations.Results: We present a family of reversible rate laws for reactions with arbitrary stoichiometries and various types of regulation, including mass-action, Michaelis-Menten and uni-uni reversible Hill kinetics as special cases. With a thermodynamically safe parameterization of these rate laws, parameter sets obtained by model fitting, sampling or optimization are guaranteed to lead to consistent chemical equilibrium states. A reformulation using saturation values yields simple formulae for rates and elasticities, which can be easily adjusted to the given stationary flux distributions. Furthermore, this formulation highlights the role of chemical potential differences as thermodynamic driving forces. We compare the modular rate laws to the thermodynamic-kinetic modelling formalism and discuss a simplified rate law in which the reaction rate directly depends on the reaction affinity. For automatic handling of modular rate laws, we propose a standard syntax and semantic annotations for the Systems Biology Markup Language.