The reason for the requirement of DHPC in M intermediate formation and fast proton release is unclear. Delipidated bR in octylglucoside is fully capable of M formation and presumably proton release, although with altered kinetics [12,16]. The requirement for pR to be in lipid to show fast H+ release and M formation stems either from a protein/lipid interaction needed to establish a stable, active tertiary structure, or from the need for the phosphate group in DHPC to act as a proton release group. The latter seems unlikely due to the DHPC molecule being zwitterionic at pH 9.5, with no proton on the trimethyl-modified nitrogen of the choline. Hence, the DHPC most likely interacts with the protein to effect minor structural changes needed to place the active site residues in their functional configuration.