Kholodenko B N
Mol Biol (Mosk). 1988 Sep-Oct;22(5):1238-56.
An attempt of a comprehensive treatment of the theory of metabolic control is presented. The introductory section giving an outline of the early development of the theory, is followed by definitions quantifying the control in the metabolic system. By means of the perturbation method the complete system of equations is obtained which allows one to express all the enzyme control coefficients ("global" coefficients) through the elasticity coefficients characterizing kinetic properties of individual enzymes ("local" coefficients) and through the steady-state values of metabolic fluxes and concentrations. It is shown how connectivity relations between global and local coefficients should be modified when conserved sums of intermediates are present in the system. A new theorem is derived, it allows one to express the global response of the system to any change in the external parameter (such as external effector concentration, or temperature, pH, ionic strength, ets.) through the control coefficients and local responses of individual reaction steps. Explicit formulas are derived for response coefficients of the fluxes and concentrations to changes in the conserved sums of intermediates, which express the values of these global coefficients through the control and elasticity coefficients of enzymes and steady-state pools. The results obtained comprise as a special case all the results published so far in the literature.
本文对代谢控制理论进行了全面的探讨。引言部分概述了该理论的早期发展，随后给出了代谢系统中控制量化的定义。通过微扰法得到了完整的方程组，该方程组使人们能够通过表征单个酶动力学特性的弹性系数（“局部”系数）以及代谢通量和浓度的稳态值来表示所有酶控制系数（“全局”系数）。展示了系统中存在中间产物守恒和时，全局系数与局部系数之间的连通性关系应如何修正。推导了一个新定理，该定理使人们能够通过控制系数和各个反应步骤的局部响应来表示系统对外部参数（如外部效应物浓度、温度、pH值、离子强度等）任何变化的全局响应。推导了通量和浓度对中间产物守恒和变化的响应系数的显式公式，这些公式通过酶的控制系数和弹性系数以及稳态库来表示这些全局系数的值。所得结果作为一个特例包含了迄今为止文献中发表的所有结果。
