Effect of evolution on the kinetic properties of enzymes.
1. 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. 2. 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. 3. 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 to the improvement of other enzymes in the metabolic pathway with regard to the criterion of an enhanced reaction flux. Such evolution is associated with an increase of the metabolite levels in the pathway, and a simple model system is examined in order to illustrate the ultimate limits for the metabolite levels and reaction flux that may obtain. 4. The theoretical evidence presented lends no support to previous proposals that certain enzymes (e.g. triosephosphate isomerase), or enzymes showing certain kinetic characteristics (e.g. kcat/Km quotients approaching 10(9) s-1 M-1), have reached the end of their evolutionary development. A claim that any specific enzyme has reached catalytic perfection would provide the unreasonable inference that all enzymes participating in intermediary metabolism have reached catalytic perfection.
Pettersson
G
G
Avdelningen för Biokemi, Kemicentrum, Lunds Universitet, Sweden.
D005075:Biological Evolution; D004058:Diffusion; D004798:Enzymes; D007700:Kinetics; D014305:Triose-Phosphate Isomerase
D004798:Enzymes; D014305:Triose-Phosphate Isomerase