Bohr effect proteins

Hemoglobin also binds H+ and C02, resulting in the formation of ion pairs that stabilize the T state and lessen the protein s affinity for 02 (the Bohr effect). Oxygen binding to hemoglobin is also modulated by 2,3-bisphosphoglycerate, which binds to and stabilizes the T state. 

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). 

When such an amino acid is incorporated into a protein, the local chemical environment in the protein may affect the pK of a group and thus alter its charge. Such changes can be very important in the function of proteins (e.g., the Bohr effect in hemoglobin depends on structural changes that affect the pK of histidine... 

Oxygen and H are not bound at the same sites in hemoglobin. Oxygen binds to the iron atoms of the hemes, whereas H binds to any of several amino acid residues in the protein. A major contribution to the Bohr effect is made by His (His HC3) of the 3 subunits. When protonated, this residue forms one of the ion pairs—to Asp (Asp FGl)—that helps stabilize deoxyhemoglobin in the T state (Fig. 5-9). The ion pair stabilizes the protonated form of His HC3, giving this residue an abnormally high piCa in the T state. The falls to its normal value of 6.0 in the R state because the ion pair cannot form, and this residue is largely unpro-... 

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