Enzyme free energy profiles: Can substrate binding be nonspontaneous? Can ground state interactions enhance catalysis?

Abstract

Two influential enzymological theories were proposed in the late 1970s - that catalytic power stems only from transition state stabilization, while ground state interactions are either irrelevant or inhibitory; and enzyme substrate binding is nonspontaneous at low substrate concentrations ([S]₀ << K_m). I show here that ground state destabilization can be a very effective source of catalytic power, especially at high substrate concentrations, and enzyme-substrate binding thermodynamics are independent of initial substrate concentration. Binding free energy ranges from negative (spontaneous) under pre-steady state conditions up to a maximum of zero at steady state. Nonspontaneous binding can only occur under standard state conditions when c° is defined to be less than K_m.

Keywords: Enzyme free energy profiles; Enzyme-substrate binding; Michaelis–Menten kinetics.