Effect of evolution on the kinetic properties of enzymes

The likely effect of a selective pressure in the direction of higher reaction fluxes on rate parameters for enzyme reactions confirming to Michaelis‐Menten kinetics has been analyzed on the basis of relationships which take into account the changes in metabolite concentrations that must be associated with mutational changes of the kinetic properties of enzymes participating in metabolic pathways. Arguments are presented to show that such a pressure should tend to increase kcat, whereas Km may decrease or increase depending on what stage of evolutionary development the enzyme has reached. While the early evolution of enzymes must have been associated with decreasing Km values, an increase of both kcat and Km is mandatory for enhancement of the rate performance of extensively developed enzymes which exhibit kcat/Km ratios approaching the diffusion‐control limit. The latter limit is dependent on the equilibrium constant for the catalysed reaction. Enzymes which have reached the diffusion‐control limit for their second‐order rate performance cannot be considered as perfectly evolved catalysts, but may well undergo further development towards a higher catalytic efficiency in response