Bohr effect involving

The transition between the T and R states of hemoglobin is also deeply involved in the Bohr effect and cooperativity. Therefore stabilization of either of the two stmctures should diminish these effects, which have important physiologic consequences. The clinical consequences of stabilization are not known. 

Protons that could logically be involved in a membrane Bohr effect are those present on imidazole rings coordinated to Fe or Cu in redox proteins. Removal of an electron from the metal ion could be accompanied by displacement of electrons within the imidazole, within a peptide group that is hydrogen-bonded to an imidazole, or within some other acidic group. A hypothetical example is illustrated in Eq. 18-12 in which a carboxyl group loses a proton when "handed" a second. If the transiently enolized peptide linkage formed in... 

The oxygen affinity of hemoglobin varies with the pH of the medium. This is the Bohr effect, and arises from the effect of pH on the interaction between the heme and the ionizable groups of the protein. It appears that the Bohr effect is linked to the presence of a second imidazole group (the distal imidazole group), which is involved in uptake of dioxygen in some indirect way. 

The most important and universal type of chemical equilibria to which a heme protein is subjected in natural environments is pH equilibria, involving the protein aminoacid residues and the ionizable groups of the porphyrin, the propionate side chains. Beside the effects on the overall protein structure, which are outside the scope of this review, the major consequences of proton equilibria may be the changes of the heme reduction potential (electron affinity), called the redox-Bohr effect (see Sect. 3.2), by analogy to the pH effect on the oxygen affinity of hemoglobin (Bohr effect). 

The number of protons involved in the redox-Bohr cooperativity was titrated, showing that this effect involves two protons [60]. Furthermore, kinetic NMR studies have shown that the intramolecular electron exchange (heme to heme) is extremely fast [61], that these two redox-Bohr protons have diffusion controlled exchange rates and that they titrate with the same pKa [54]. 

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