Evolutionary optimization of the catalytic efficiency of enzymes

The rate equation for a generalized Michaelian type of enzymic reaction mechanism has been analyzed in order to establish how the mechanism should be kinetically designed in order to optimize the catalytic efficiency of the enzyme for a given average magnitude of true and apparent first‐order rate constants in the mechanism at given concentrations of enzyme, substrate and product. As long as on‐velocity constants for substrate and product binding to the enzyme have not reached the limiting value for a diffusion‐controlled association process, the optimal state of enzyme operation will be characterized by forward (true and apparent) first‐order rate constants of equal magnitude and reverse rate constants of equal magnitude. The drop in free energy driving the catalysed reaction will occur to an equal extent for each reaction step in the mechanism. All internal equilibrium constants will be of equal magnitude and reflect only the closeness of the catalysed reaction to equilibrium conditions. When magnitudes of on‐velocity constants for substrate and product binding have reached their upper limits, the optimal kinetic design of the reaction mechanism becomes more complex and has to