IMPOSED OSCILLATIONS OF KINETIC BARRIERS CAN CAUSE AN ENZYME TO DRIVE A CHEMICAL-REACTION AWAY FROM EQUILIBRIUM

The overall Gibbs free energy change (DELTAG) of a chemical reaction is often termed the driving force of the reaction. The sign of DELTAG defines the direction of spontaneous reaction, and the condition DELTAG = 0 defines the point of chemical equilibrium. This is strictly true for elementary reactions-reactions that pass through only one local maximum (the transition state) along the reaction coordinate connecting reactant and product states. However, under many circumstances it is also true for reactions that involve one or more intermediates, particularly if the steady state intermediate concentrations are very small. Here we show that externally imposed oscillations or fluctuations can drive a net chemical reaction away from equilibrium so long as the rate constants of at least one elementary step of the overall reaction depend on the fluctuating parameter. This is true even if the overall DELTAG is independent of the perturbation and it is also true even if the concentrations of the intermediate states are very, very small (i.e., experimentally undetectable). The key to understanding this result is to realize that the imposed oscillation does work on the intermediate states of the reaction. Even if the concentrations of the intermediates are very small, this work can accumulate over many cycles of oscillation, leading to a significant shift of the net reaction away from equilibrium. Our results demonstrate that the addition of an enzyme (or any catalyst) to a chemical reaction initially at equilibrium (but exposed to an oscillating field) may cause the reaction to proceed away from equilibrium. This provides an explicit counter example to the adage that the addition of a small amount of catalyst to a chemical reaction at equilibrium cannot cause the reaction to go away a from equilibrium.