Kinetic parameters of enzymatic reactions in states of maximal activity; an evolutionary approach.

A theoretical investigation is presented which allows the calculation of states of maximal reaction rates for single enzymes and for unbranched enzymatic chains. As an extension to previous papers (Heinrich & Holzhütter, 1985, Biomed. biochim. Acta 44, 959-969; Heinrich et al., 1987, Bull. math. Biol. 49, 539-595) a detailed enzymatic mechanism was taken into consideration. Conclusions are drawn for the optimal values of the microscopic rate constants as well as of the maximal activities and Michaelis constants. Ten solutions are found which depend on the equilibrium constant as well as on the concentrations of substrates and products. It is shown that for high equilibrium constants one of the solutions applies to a very large range of the concentrations of the outer reactants. This solution is characterized by maximal values of the rate constants of all forward reactions and by non-maximal values of the rate constants of all backward reactions. In contrast to previous assumptions (Albery & Knowles, 1976b, Biochemistry 15, 5631-5640; Burbaum et al., 1989, Biochemistry 28, 9293-9305) states of maximal reaction rate are not always characterized by the highest possible values of the second-order rate constants which are related to the diffusion of the substrate and the product to the active site of the enzyme. Predictions are made concerning the ratios of maximal activities in optimal states as well as for the adaptation of the Michaelis constants to the concentrations of the outer reactants. Using metabolic control analysis it is shown that the solutions obtained for single enzymes may also be applied in multi-enzyme systems.