Efficiency and design of simple metabolic systems.

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.