Bohr effect
The Bohr effect is a phenomenon first described in 1904 by the Danish physiologist
Experimental discovery
In the early 1900s, Christian Bohr was a professor at the
Controversy
There is some more debate over whether Bohr was actually the first to discover the relationship between CO2 and oxygen affinity, or whether the Russian physiologist Bronislav Verigo beat him to it, allegedly discovering the effect in 1898, six years before Bohr.[6] While this has never been proven, Verigo did in fact publish a paper on the haemoglobin-CO2 relationship in 1892.[7] His proposed model was flawed, and Bohr harshly criticized it in his own publications.[1]
Another challenge to Bohr's discovery comes from within his lab. 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.[4]
Physiological role
The Bohr effect increases the efficiency of oxygen transportation through the blood. After hemoglobin binds to oxygen in the lungs due to the high oxygen concentrations, the Bohr effect facilitates its release in the tissues, particularly those tissues in most need of oxygen. When a tissue's metabolic rate increases, so does its carbon dioxide waste production. When released into the bloodstream, carbon dioxide forms bicarbonate and protons through the following reaction:
Although this reaction usually proceeds very slowly, the enzyme
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
Strength of the effect and body size
The magnitude of the Bohr effect is usually given by the slope of the vs curve where, P50 refers to the partial pressure of oxygen when 50% of haemoglobin's binding sites are occupied. The slope is denoted: where denotes change. That is, denotes the change in and the change in . Bohr effect strength exhibits an inverse relationship with the size of an organism: the magnitude increases as size and weight decreases. For example, mice possess a very strong Bohr effect, with a value of -0.96, which requires relatively minor changes in H+ or CO2 concentrations, while elephants require much larger changes in concentration to achieve a much weaker effect .[9]
Mechanism
Allosteric interactions
T-state stabilization
When hemoglobin is in its T state, the
Carbon dioxide can also react directly with the N-terminal amino groups to form
CO2 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.[2]
Special cases
Marine mammals
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] However, when their blood was examined, this was not the case. Humpback whales weighing 41,000 kilograms had an observed value of 0.82, which is roughly equivalent to the Bohr effect magnitude in a 0.57 kg guinea pig.[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.[12] Examination of other marine mammal species supports this. In pilot whales and porpoises, which are primarily surface feeders and seldom dive for more than a few minutes, the was 0.52, comparable to a cow,[9] which is much closer to the expected Bohr effect magnitude for animals of their size.[12]
Carbon monoxide
Another special case of the Bohr effect occurs when carbon monoxide is present. This molecule serves as a competitive inhibitor for oxygen, and binds to haemoglobin to form carboxyhaemoglobin.[13] Haemoglobin's affinity for CO is about 210 times stronger than its affinity for O2,[14] meaning that it is very unlikely to dissociate, and once bound, it blocks the binding of O2 to that subunit. 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. It is most pronounced when the oxygen concentration is extremely low, as a last-ditch effort when the need for oxygen delivery becomes critical. However, the physiological implications of this phenomenon remain unclear.[13]
See also
References
- ^ a b c d Bohr; Hasselbalch, Krogh. "Concerning a Biologically Important Relationship - The Influence of the Carbon Dioxide Content of Blood on its Oxygen Binding".
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(help) - ^ a b c d e f Voet, Donald; Judith G. Voet; Charlotte W. Pratt (2013). Fundamentals of Biochemistry: Life at the Molecular Level (4th ed.). John Wiley & Sons, Inc. p. 189.
- ^ ISSN 0362-1197.
- ^ S2CID 751105.
- ^ G. Hüfner, "Ueber das Gesetz der Dissociation des Oxyharmoglobins und über einige daran sich knupfenden wichtigen Fragen aus der Biologie," [On the Law of the Dissociation of Oxyharmoglobin, and on some important questions arising from biology]. Arch. Anat. Physiol. (in German) (Physiol. Abtheilung) (1890), 1-27.
- ^ "Вериго эффект - это... Что такое Вериго эффект?" [Verigo effect is... What is the Verigo effect?]. Словари и энциклопедии на Академике (in Russian). Retrieved 2016-11-08.
- ^ B. Werigo, "Zur Frage uber die Wirkung des Sauerstoffs auf die Kohlensaureausscheidung in den Lungen," [The question about the effect of oxygen on the secretion of carbonic acid in the lungs]. Pflügers Arch. ges. Physiol. (in German), 51 (1892), 321-361.
- ^ A. Krogh, "Apparat und Methoden zur Bestimmung der Aufnahme von Gasen im Blute bei verschiedenen Spannungen der Gase," [Apparatus and methods for the determination of the absorption of gases in the blood at different tensions of the gases]. Skand. Arch. Physiol. (in German), 16 (1904), 390-401.
- ^ PMID 19873527.
- ISBN 9789814498517.
- PMID 4636319.
- ^ S2CID 26899569.
- ^ PMID 12132.
- ISBN 978-1416045748.