A model for the enzyme activity in systems with large composition fluctuations. An application to the unusual kinetics of phospholipase A₂

Abstract:

A non-equilibrium thermodynamics based model is proposed in order to describe the role of large concentration fluctuations of enzymes, reactants and products in modulating the macroscopic time evolution of chemical kinetics. The encounter probabilities between reactants and enzyme depend on their local concentration. Fluctuations modify the bimolecular encounter probability. Since, in turn, the amplitude of fluctuations depends itself on the instantaneous composition of the reacting mixture, the time-varying chemical composition acts as a positive feedback mechanism for the reactive fluid mixture near the critical temperature for phase separation. The model is applied to rationalize the unusual features of phospholipase A₂ kinetics, an enzyme which catalyzes the hydrolisis of membrane forming phospholipids, yielding products which are still soluble in the lipid matrix. A typical feature of the enzyme reaction is the long induction time prior to a ”burst” of activity. This effect is well reproduced by the theory, together with the dependence of the induction time on the exogeneous addition of products or other liposoluble substances, the effects of enzyme and substrate concentration, and the temperature dependence of the enzyme activation. All these properties emerge as a consequence of the coupling between enconter probability and time-varying bilayer heterogeneity. A good qualitative agreement between theoretical results and the available experimental results has been generally found.