In allosteric interactions, the binding of a molecule to one site on the protein leads to conformational changes that affect a distant site on the protein. In hemoglobin, O2 binding is cooperative (the first binding enhances additional binding by the other heme groups nested in the other polypeptide chains). Cooperative binding in hemoglobin has found its way onto many MCATs. Additionally, the binding of H+ or CO2 allosterically alters the binding of O2. The allosteric changes in hemoglobin occur through subunit interaction. Most allosteric changes occur by means of quaternary structure. O2 binding relaxes the hemoglobin tetramer, promoting additional binding. The molecule BPG decreases affinity by stabilizing the deoxyhemoglobin quaternary structure. CO2 binding occurs at the terminal amino groups which take up carbamate to form salt bridges which stabilize deoxyhemoglobin. Furthermore, with deoxyhemoglobin, a certain histidine side chain gains affinity for H+, so acidic conditions stabilize deoxyhemoglobin.
These effects are summarized in the MCAT favorite discussion of the Bohr effect. Basically, an increase in blood carbon dioxide level, a decrease in pH or increase in temperature leads hemoglobin to bind oxygen less strongly. The Bohr effect supports the oxygen transport function of hemoglobin. Hemoglobin binds to oxygen in the lungs, but then releases it in the tissues, where carbon dioxide levels are high and pH is low.