Editing Bohr effect (section)

== Mechanism ==
=== Allosteric interactions ===
[[File:Hemoglobin t-r state ani.gif|thumb|278x278px|Haemoglobin changes conformation from a high-affinity R state (oxygenated) to a low-affinity T state (deoxygenated) to improve oxygen uptake and delivery.]]The Bohr effect hinges around allosteric interactions between the [[heme]]s of the haemoglobin [[Tetrameric protein|tetramer]], a mechanism first proposed by [[Max Perutz]] in 1970.<ref>{{Cite book|title=Science is Not a Quiet Life|last=Perutz|first=Max|publisher=World Scientific|isbn=9789814498517|date=1998-01-15}}</ref> Haemoglobin exists in two conformations: a high-affinity R state and a low-affinity T state. When oxygen concentration levels are high, as in the lungs, the R state is favored, enabling the maximum amount of oxygen to be bound to the hemes. In the capillaries, where oxygen concentration levels are lower, the T state is favored, in order to facilitate the delivery of oxygen to the tissues. The Bohr effect is dependent on this allostery, as increases in CO<sub>2</sub> and H<sup>+</sup> help stabilize the T state and ensure greater oxygen delivery to muscles during periods of elevated cellular respiration. This is evidenced by the fact that [[myoglobin]], a [[monomer]] with no allostery, does not exhibit the Bohr effect.<ref name="Voet" /> Haemoglobin mutants with weaker allostery may exhibit a reduced Bohr effect. For example, in Hiroshima variant [[haemoglobinopathy]], allostery in haemoglobin is reduced, and the Bohr effect is diminished. As a result, during periods of exercise, the mutant haemoglobin has a higher affinity for oxygen and tissue may suffer minor [[Hypoxia (medical)|oxygen starvation]].<ref>{{cite journal | last=Olson | first=JS |author2=Gibson QH|author3=Nagel RL|author4=Hamilton HB| title=The ligand-binding properties of hemoglobin Hiroshima ( 2 2 146asp )| journal=The Journal of Biological Chemistry | volume=247 | issue=23 | pages=7485–93 | date=December 1972 | doi=10.1016/S0021-9258(19)44551-1 | pmid=4636319| doi-access=free }}</ref>

=== T-state stabilization ===
When hemoglobin is in its T state, the [[N-terminal]] amino groups of the α-subunits and the [[C-terminal]] [[histidine]] of the β-subunits are protonated, giving them a positive charge and allowing these residues to participate in [[Ionic bonding|ionic interactions]] with carboxyl groups on nearby residues. These interactions help hold the haemoglobin in the T state. Decreases in pH (increases in acidity) stabilize this state even more, since a decrease in pH makes these residues even more likely to be protonated, strengthening the ionic interactions. In the R state, the ionic pairings are absent, meaning that the R state's stability increases when the pH increases, as these residues are less likely to stay protonated in a more basic environment. The Bohr effect works by simultaneously destabilizing the high-affinity R state and stabilizing the low-affinity T state, which leads to an overall decrease in oxygen affinity.<ref name="Voet" /> This can be visualized on an [[Oxygen–hemoglobin dissociation curve|oxygen-haemoglobin dissociation curve]] by shifting the whole curve to the right.

Carbon dioxide can also react directly with the N-terminal amino groups to form [[carbamates]], according to the following reaction:
: <chem>R-NH2 + CO2 <=> R-NH-COO^- + H+</chem>
CO<sub>2</sub> forms carbamates more frequently with the T state, which helps to stabilize this conformation. The process also creates protons, meaning that the formation of carbamates also contributes to the strengthening of ionic interactions, further stabilizing the T state.<ref name="Voet" />