863—Absorption and conversion of electric field energy by membrane bound ATPases

Abstract

Electric fields are ubiquitous in living organisms, yet, little is known of their effects on the function of enzymes and proteins. Recent experiments show that applied electric fields can induce active transport of K+, Rb+ and Ca2+ by transport-ATPases, as well as ATP synthesis by ATP-synthetases. In all cases, tightly sealed membrane vesicles have been essential. Here we present a kinetic model for the transduction of electric field energy based on three considerations: The equilibrium between any two conformational states of a protein is susceptible to perturbation by an electric field so long as there exists a difference between the molar electric moments. An integral membrane protein experiences an amplified electric field. The transmembrane potential is maintained only with non-leaky vesicles. This model consists of four steps to form a complete cycle (i.e. one enzyme turnover), namely, the conformational energy coupling (energy absorption), the substrate binding, the energy transduction (energy conversion), and the product release steps. The energy transduction step is mediated by reversal of the local field. Computer simulations show that this four state model converts electric field energy into chemical potential energy if the frequency and the strength of the applied field properly match the characteristics of the system. The model finds analogy in an electric rectifier, which conducts current only in certain directions. The results of simulation agree with the main features of the experimental data for voltage-stimulated active transport of Rb+via (Na,K)ATPase of erythrocytes. The concept is extended to the interpretation of data for the voltage-induced ATP synthesis by ATP-synthetases. In this case, F0 is treated as a voltage modulating subunit whose function is to effect a periodic attenuation of the local electric field. This modulation allows multiple enzyme turnover even when a d.c. field is imposed. For the in vivo ATP synthesis, the membrane potential (d.c. in nature) presumably is supplied by the electron transport reactions. Reduction of cytochromes reconstituted into the lipid bilayer is well known to generate transmembrane potentials. The model treats the energy coupling event as a field-induced conformational change, and reduces energy transduction to events pertinent to the study of molecular mechanisms of enzyme action. The equations derived are solidly based on fundamental thermodynamic principles.