Heinrich R, Holzhütter H G
Biomed Biochim Acta. 1985;44(6):959-69.
A theoretical approach to the explanation of the structural design of metabolic pathways is presented. It is based on the hypothesis that due to natural selection during evolution the cellular metabolism of present-day organisms may be characterized by optimal properties. Two cardinal terms enter the theory: 1) the efficiency of metabolic pathways and 2) the evolutionary effort for the change of the kinetic parameters of the involved enzymes by mutations of the corresponding genes. For both quantities simple mathematical expressions are proposed. By maximizing the efficiency under the constraint of a constant evolutionary effort the theory allows the calculation of the optimal parameter distribution. The theoretical concept is applied to simple metabolic systems consisting of monomolecular reactions only. It is shown that in the optimal state of the linear enzymatic chain the evolutionary effort is mainly spent on the enzymes located at the beginning of the chain. This tendency is more pronounced if the kinetic equations of the enzymes are first-order rate laws. With respect to Michaelis-Menten enzymes the optimal state is characterized by a decrease of the maximal activities and an increase of the fractional saturation of the enzymes towards the end of the chain.
本文提出了一种解释代谢途径结构设计的理论方法。该方法基于这样一种假设：由于进化过程中的自然选择，当今生物体的细胞代谢可能具有最优特性。该理论引入了两个基本概念：1）代谢途径的效率；2）通过相应基因突变改变相关酶动力学参数的进化努力。针对这两个量，提出了简单的数学表达式。通过在恒定进化努力的约束下最大化效率，该理论允许计算最优参数分布。该理论概念应用于仅由单分子反应组成的简单代谢系统。结果表明，在线性酶链的最优状态下，进化努力主要花费在位于链起始位置的酶上。如果酶的动力学方程是一级速率定律，这种趋势会更加明显。对于米氏酶，最优状态的特征是链末端酶的最大活性降低，分数饱和度增加。
