Effects of oscillations and energy-driven fluctuations on the dynamics of enzyme catalysis and free-energy transduction

Abstract

It has been shown that many enzymes should be capable of utilizing free energy supplied by external time-dependent perturbations to drive the chemical or transport reactions they catalyze away from equilibrium. This property is analyzed in terms of thermodynamic and kinetic theory. An explicit demonstration using irreversible thermodynamics, through second order, is given for the case of a simple model enzyme in the presence of a periodic external perturbation. Three reasons for an enzyme to drive a reaction in a nonstationary environment may be identified: the average values of the forces, the root mean square of the external time-dependent perturbation, and the frequency-dependent correlation between the applied perturbation and the enzyme response. The extent to which the output reaction responds to any of these is governed by the kinetic constants of the enzyme. Even if the catalyzed reaction (e.g., the transport of an uncharged substance across a membrane) is in and of itself thermodynamically independent of the periodic perturbation (e.g., an ac electric field), the enzyme is competent to mediate free-energy exchange between the two. This originates from the fact that at high frequencies, the enzyme response lags behind the applied perturbation. It is sufficient that the enzyme interact with the applied field, and that the catalytic rate constants display the kinetic asymmetry typical of many, and particularly transport, enzymes. These results highlight the role of enzymes as free-energy converters in addition to that of biological catalysts.