On the mechanism of proton translocation by respiratory enzyme

The protonmotive function of the respiratory heme-copper oxidases is often described as the sum of two separate mechanisms: a proton pump plus an incomplete Mitchellian redox loop. However, these two functions may be mechanistically intertwined so that the uptake of protons to form water during the reduction of O-2 is a crucial part of the proton pump mechanism itself. This principle can be deduced from thermodynamic, kinetic, mechanistic, as well as from structural considerations, and was first proposed in conjunction with a histidine cycle model of proton translocation [Morgan, J. E., Verkhovsky, M. I., and Wikstrom, M. (1994). J. Bioenerg. Biomembr. 26, 599-608]. However, histidine cycle models go much further to suggest chemical details of how this principle might be applied.