Kinetic model of ATP synthase: pH dependence of the rate of ATP synthesis

Abstract

Recently, a novel molecular mechanism of torque generation in the F 0 portion of ATP synthase was proposed [Rohatgi, Saha and Nath (1998) Curr. Sci. 75, 716–718]. In this mechanism, rotation of the c-subunit was conceived to take place in 12 discrete steps of 30° each due to the binding and unbinding of protons to/from the leading and trailing Asp-61 residues of the c-subunit, respectively. Based on this molecular mechanism, a kinetic scheme has been developed in this work. The scheme considers proton transport driven by a concentration gradient of protons across the proton half-channels, and the rotation of the c-subunit by changes in the electrical potential only. This kinetic scheme has been analyzed mathematically and an expression has been obtained to explain the pH dependence of the rate of ATP synthesis by ATP synthase under steady state operating conditions. For a single set of three enzymological kinetic parameters, this expression predicts the rates of ATP synthesis which agree well with the experimental data over a wide range of pH in and pH out. A logical consequence of our analysis is that ΔpH and Δ ψ are kinetically inequivalent driving forces for ATP synthesis.