The D-channel of cytochrome oxidase: An alternative view

► We present a critical analysis of the properties of the so-called D-pathway of proton transfer in the A-type heme-copper oxidases. ► The role of the D-pathway in proton translocation is analysed in terms of side chain isomerisation of the residue Glu286. ► The rate of proton transfer in the D-pathway depends on the product of the rate constant (k)that may be changed by mutations, and the occupancy of the protonated form of Asp132 at the channel orifice.