Acerenza L, Kacser H
Department of Genetics, University of Edinburgh, U.K.
Biochem J. 1990 Aug 1;269(3):697-707. doi: 10.1042/bj2690697.
It is usual to study the sensitivity of metabolic variables to small (infinitesimal) changes in the magnitudes of individual parameters such as an enzyme concentration. Here, the effect that a simultaneous change in all the enzyme concentrations by the same factor alpha (Co-ordinate-Control Operation, CCO) has on the variables of time-dependent metabolic systems is investigated. This factor alpha can have any arbitrary large value. First, we assume, for each enzyme measured in isolation, the validity of the steady-state approximation and the proportionality between reaction rate and enzyme concentration. Under these assumptions, any time-invariant variable may behave like a metabolite concentration, i.e. S alpha = Sr (S-type), or like a flux, i.e. J alpha = alpha Jr (J-type). The subscripts r and alpha correspond to the values of the variable before and after the CCO respectively. Similarly, time-dependent variables may behave according to S alpha (t/alpha) = Sr (t) (S-type) or to J alpha (t/alpha) = alpha J r (t) (J-type). A method is given to test these relationships in experimental systems, and to quantify deviations from the predicted behaviour. A positive test for deviations proves the violation of some of the assumptions made. However, the breakdown of the assumptions in an enzyme-catalysed reaction, studied in isolation, may or may not affect significantly the behaviour of the system when the component reaction is embedded in the metabolic network.
通常会研究代谢变量对单个参数（如酶浓度）大小的微小（无穷小）变化的敏感性。在此，研究了所有酶浓度同时以相同因子α变化（协同控制操作，CCO）对时间依赖性代谢系统变量的影响。这个因子α可以取任意大的值。首先，对于单独测量的每种酶，我们假设稳态近似的有效性以及反应速率与酶浓度之间的比例关系。在这些假设下，任何时间不变变量的行为可能类似于代谢物浓度，即Sα = Sr（S型），或者类似于通量，即Jα = αJr（J型）。下标r和α分别对应于CCO前后变量的值。类似地，时间依赖性变量的行为可能符合Sα(t/α) = Sr(t)（S型）或Jα(t/α) = αJr(t)（J型）。给出了一种在实验系统中测试这些关系并量化与预测行为偏差的方法。对偏差的阳性测试证明违反了所做的一些假设。然而，在单独研究的酶催化反应中假设的失效，当组成反应嵌入代谢网络时，可能会也可能不会显著影响系统的行为。
