Bohr effect

Hemoglobin Dissociation Curve. Dotted red line corresponds with shift to the right caused by Bohr effect

Bohr effect is a property of hemoglobin first described in 1904 by the Danish physiologist Christian Bohr (father of physicist Niels Bohr), which states that at lower pH (more acidic environment), hemoglobin will bind to oxygen with less affinity. Since carbon dioxide is in direct equilibrium with the concentration of protons in the blood, increasing blood carbon dioxide levels leads to a decrease in pH, which ultimately leads to a decrease in affinity for oxygen by hemoglobin.

Proton and oxygen coupling

In deoxyhemoglobin, the N-terminal amino groups of the α-subunits and the C-terminal Histidine of the β-subunits participate in ion pairs. The formation of ion pairs causes them to decrease in acidity. Thus, deoxyhemoglobin binds one proton for every two O₂ released. In oxyhemoglobin, these ion pairings are absent and these groups increase in acidity. Consequentially, a proton is released for every two O₂ bound. Specifically, this reciprocal coupling of protons and oxygen is the Bohr effect. ^[1]

Physiological role

This effect facilitates oxygen transport as hemoglobin binds to oxygen in the lungs, but then releases it in the tissues, particularly those tissues in most need of oxygen. When a tissue's metabolic rate increases, its carbon dioxide production increases. Carbon dioxide forms bicarbonate through the follow reaction:

CO₂ + H₂O H₂CO₃ H⁺ + HCO₃⁻

Although the reaction usually proceeds very slowly, the enzyme family, carbonic anhydrase in red blood cells accelerates the formation of bicarbonate and protons. This causes the pH of the tissue to decrease, and so, promotes the dissociation of oxygen from hemoglobin to the tissue, allowing the tissue to obtain enough oxygen to meet its demands. Conversely, in the lungs, where oxygen concentration is high, binding of oxygen causes hemoglobin to release protons, which combine with bicarbonate to drive off carbon dioxide in exhalation. Since these two reactions are closely matched, there is little change in blood pH.

The dissociation curve shifts to the right when carbon dioxide or hydrogen ion concentration is increased. This facilitates increased oxygen dumping. This mechanism allows for the body to adapt the problem of supplying more oxygen to tissues that need it the most. When muscles are undergoing strenuous activity, they generate CO₂ and lactic acid as products of cellular respiration and lactic acid fermentation. In fact, muscles generate lactic acid so quickly that pH of the blood passing through the muscles will drop to around 7.2. As lactic acid releases its protons, pH decreases, which causes hemoglobin to release ~10% more oxygen. ^[2]

Carbamates

Carbon dioxide modulates O₂ binding to hemoglobin directly by combining reversibly to N-terminal amino groups of blood proteins to form carbamates:

R−NH₂ + CO₂ R−NH−COO^- + H⁺

Deoxyhemoglobin binds to CO₂ more readily to form a carbamate than oxyhemoglobin. When CO₂ concentration is high (as in the capillaries), the protons released by carbamate formation further promotes oxygen release. Although the difference in CO₂ binding between the oxy and deoxy states of hemoglobin accounts for only 5% of the total blood CO₂, it is responsible for half of the CO₂ transported by blood. This is because 10% of the total blood CO₂ is lost through the lungs in each circulatory cycle. ^[2]

Effects of cooperativity

The Bohr effect is dependent on cooperative interactions between the hemes of the hemoglobin tetramer. This is evidenced by the fact that myoglobin, a monomer with no cooperativity, does not exhibit the Bohr effect. Hemoglobin mutants with weaker cooperativity may exhibit a reduced Bohr effect.

In the Hiroshima variant hemoglobinopathy, cooperativity in hemoglobin is reduced, and the Bohr effect is diminished. During periods of exercise, the mutant hemoglobin has a higher affinity for oxygen and tissue may suffer minor oxygen starvation. ^[3]

See also

Haldane Effect

References

1. ^ Murray, Robert K.; Darryl K. Granner, Peter A. Mayes, Victor W. Rodwell (2003). Harper’s Illustrated Biochemistry (LANGE Basic Science) (26th ed.). McGraw-Hill Medical. p. 44-45. 
2. ^ ^{a b} Voet, Donald; Judith G. Voet, Charlotte W. Pratt (2008). Fundamentals of Biochemistry: Life at the Molecular Level (3rd ed.). John Wiley & Sons. p. 189-190. 
3. ^ Olson, JS; Gibson QH, Nagel RL, Hamilton HB (December 1972). "The ligand-binding properties of hemoglobin Hiroshima ( 2 2 146asp )". The Journal of Biological Chemistry 247 (23): 7485–93. PMID 4636319. 

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