Bohr effect

Hemoglobin's oxygen binding affinity (see oxygen–haemoglobin dissociation curve) is inversely related both to acidity and to the concentration of carbon dioxide.

[1] That is, the Bohr effect refers to the shift in the oxygen dissociation curve caused by changes in the concentration of carbon dioxide or the pH of the environment.

Conversely, a decrease in carbon dioxide provokes an increase in pH, which results in hemoglobin picking up more oxygen.

In the early 1900s, Christian Bohr was a professor at the University of Copenhagen in Denmark, already well known for his work in the field of respiratory physiology.

[4] Further experimentation while varying the CO2 concentration quickly provided conclusive evidence, confirming the existence of what would soon become known as the Bohr effect.

Though Bohr was quick to take full credit, his associate Krogh, who invented the apparatus used to measure gas concentrations in the experiments,[8] maintained throughout his life that he himself had actually been the first to demonstrate the effect.

Though there is some evidence to support this, retroactively changing the name of a well-known phenomenon would be extremely impractical, so it remains known as the Bohr effect.

When released into the bloodstream, carbon dioxide forms bicarbonate and protons through the following reaction: Although this reaction usually proceeds very slowly, the enzyme carbonic anhydrase (which is present in red blood cells) drastically speeds up the conversion to bicarbonate and protons.

These opposing protonation and deprotonation reactions occur in equilibrium resulting in little overall change in blood pH.

The Bohr effect enables the body to adapt to changing conditions and makes it possible to supply extra oxygen to tissues that need it the most.

For example, when muscles are undergoing strenuous activity, they require large amounts of oxygen to conduct cellular respiration, which generates CO2 (and therefore HCO3− and H+) as byproducts.

These waste products lower the pH of the blood, which increases oxygen delivery to the active muscles.

The Bohr effect hinges around allosteric interactions between the hemes of the haemoglobin tetramer, a mechanism first proposed by Max Perutz in 1970.

The Bohr effect is dependent on this allostery, as increases in CO2 and H+ help stabilize the T state and ensure greater oxygen delivery to muscles during periods of elevated cellular respiration.

For example, in Hiroshima variant haemoglobinopathy, allostery in haemoglobin is reduced, and the Bohr effect is diminished.

[11] 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 interactions with carboxyl groups on nearby residues.

The process also creates protons, meaning that the formation of carbamates also contributes to the strengthening of ionic interactions, further stabilizing the T state.

[2] An exception to the otherwise well-supported link between animal body size and the sensitivity of its haemoglobin to changes in pH was discovered in 1961.

[12] Based on their size and weight, many marine mammals were hypothesized to have a very low, almost negligible Bohr effect.

[9] This extremely strong Bohr effect is hypothesized to be one of marine mammals' many adaptations for deep, long dives, as it allows for virtually all of the bound oxygen on haemoglobin to dissociate and supply the whale's body while it is underwater.

was 0.52, comparable to a cow,[9] which is much closer to the expected Bohr effect magnitude for animals of their size.

This molecule serves as a competitive inhibitor for oxygen, and binds to haemoglobin to form carboxyhaemoglobin.

At the same time, CO is structurally similar enough to O2 to cause carboxyhemoglobin to favor the R state, raising the oxygen affinity of the remaining unoccupied subunits.

This combination significantly reduces the delivery of oxygen to the tissues of the body, which is what makes carbon monoxide so toxic.

This toxicity is reduced slightly by an increase in the strength of the Bohr effect in the presence of carboxyhemoglobin.

This increase is ultimately due to differences in interactions between heme groups in carboxyhemoglobin relative to oxygenated hemoglobin.

Christian Bohr, who was credited with the discovery of the effect in 1904.
The original dissociation curves from Bohr's experiments in the first description of the Bohr effect, showing a decrease in oxygen affinity as the partial pressure of carbon dioxide increases. This is also one of the first examples of cooperative binding . X-axis: oxygen partial pressure in mmHg , Y-axis % oxy-hemoglobin . The curves were obtained using whole dog blood , with the exception of the dashed curve, for which horse blood was used.
The magnitude of the Bohr effect is given by , which is the slope on this graph. A steeper slope means a stronger Bohr effect.
Haemoglobin changes conformation from a high-affinity R state (oxygenated) to a low-affinity T state (deoxygenated) to improve oxygen uptake and delivery.
Though they are one of the largest animals on the planet, humpback whales have a Bohr effect magnitude similar to that of a guinea pig.