A simple back-of-the-envelope calculation says that the protonation of a residue (e.g. raising its pKa from 5 to 9) costs ca. 5.7 kcal/mol (~250 meV) of energy. This, together with the uptake of a proton from the N phase to the E channel, which is roughly half of the membrane dielectric, would require an additional ~100 meV at a maximal proton motive force of 200 mV. Thus, the first few initial cycles of NADH oxidation and Q reduction would be sufficient to load the E channel/membrane domain (as well as for energy costs associated with structural change) to its full proton loading capacity, priming the enzyme for turnover A state, where Q reduction is tightly coupled to proton pumping. The hypothesis is also supported by the fact that at high pH (higher occupancy of deprotonated state of amino acid residues), transition from D to A state is further prolonged . All in all, we suggest that reaching the correct protonation state of the membrane arm for pumping might be a yet unidentified element of the A/D transition.