Do enzymes bind their substrates in the ground state because of a physico-chemical requirement?
Transition state theory has provided no convincing explanation for the nearly universal observation of complexes of enzymes with substrates. Bimolecular catalytic reactions are assumed here to take place through reactive encounter complexes defined as the subset of reactant state species able to proceed directly to low lying energy levels at the transition state. By assessing the probability of these complexes from the maximum efficiency of intramolecular reactions, an upper limit for the rate constants promoted by hypothetical catalysts unable to bind substrates is deduced. This limit, which is below the ordinary range of bimolecular rate constants (k(cat)/K(M)) for enzyme reactions, results from a kinetic limitation in the formation of reactive encounter complexes. Exceeding this limit requires a stabilization of these complexes. Using the terminology of transition state theory, the need for enzymes to form complexes with substrates is then expressed as a necessity to restore Boltzmann distribution at the transition state.
Pascal
Robert
R
UMR 5073, CC 017, Département de Chimie, Université Montpellier 2, Place Eugène Bataillon, F-34095, Montpellier cedex 5, France. rpascal@univ-montp2.fr
D002384:Catalysis; D004795:Enzyme Stability; D004798:Enzymes / Q000737:chemistry*; D007700:Kinetics; D013379:Substrate Specificity; D013816:Thermodynamics
D004798:Enzymes