Oxygen–hemoglobin dissociation curve
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The oxygen–hemoglobin dissociation curve, also called the oxyhemoglobin dissociation curve or oxygen dissociation curve (ODC), is a
Background
Hemoglobin (Hb) is the primary vehicle for transporting oxygen in the blood. Each hemoglobin molecule has the capacity to carry four oxygen molecules. These molecules of oxygen bind to the iron of the heme prosthetic group.[1]
When hemoglobin has no bound oxygen, nor bound carbon dioxide, it has the unbound conformation (shape). The binding of the first oxygen molecule induces change in the shape of the hemoglobin that increases its ability to bind to the other three oxygen molecules.
In the presence of dissolved carbon dioxide, the pH of the blood changes; this causes another change in the shape of hemoglobin, which increases its ability to bind carbon dioxide and decreases its ability to bind oxygen. With the loss of the first oxygen molecule, and the binding of the first carbon dioxide molecule, yet another change in shape occurs, which further decreases the ability to bind oxygen, and increases the ability to bind carbon dioxide. The oxygen bound to the hemoglobin is released into the blood's plasma and absorbed into the tissues, and the carbon dioxide in the tissues is bound to the hemoglobin.
In the
Oxygen is also carried dissolved in the blood's plasma, but to a much lesser degree. Hemoglobin is contained in red blood cells. Hemoglobin releases the bound oxygen when carbonic acid is present, as it is in the tissues. In the capillaries, where carbon dioxide is produced, oxygen bound to the hemoglobin is released into the blood's plasma and absorbed into the tissues.
How much of that capacity is filled by oxygen at any time is called the
Sigmoid shape
The curve is usually best described by a sigmoid plot, using a formula of the kind:
A hemoglobin molecule can bind up to four oxygen molecules in a reversible method.
The shape of the curve results from the interaction of bound oxygen molecules with incoming molecules. The binding of the first molecule is difficult. However, this facilitates the binding of the second, third and fourth, this is due to the induced conformational change in the structure of the hemoglobin molecule induced by the binding of an oxygen molecule.
In its simplest form, the oxyhemoglobin dissociation curve describes the relation between the partial pressure of oxygen (x axis) and the oxygen saturation (y axis). Hemoglobin's affinity for oxygen increases as successive molecules of oxygen bind. More molecules bind as the oxygen partial pressure increases until the maximum amount that can be bound is reached. As this limit is approached, very little additional binding occurs and the curve levels out as the hemoglobin becomes saturated with oxygen. Hence the curve has a sigmoidal or S-shape. At pressures above about 60 mmHg, the standard dissociation curve is relatively flat, which means that the oxygen content of the blood does not change significantly even with large increases in the oxygen partial pressure. To get more oxygen to the tissue would require blood transfusions to increase the hemoglobin count (and hence the oxygen-carrying capacity), or supplemental oxygen that would increase the oxygen dissolved in plasma. Although binding of oxygen to hemoglobin continues to some extent for pressures about 50 mmHg, as oxygen partial pressures decrease in this steep area of the curve, the oxygen is unloaded to peripheral tissue readily as the hemoglobin's affinity diminishes. The partial pressure of oxygen in the blood at which the hemoglobin is 50% saturated, typically about 26.6 mmHg (3.5 kPa) for a healthy person, is known as the
The 'plateau' portion of the oxyhemoglobin dissociation curve is the range that exists at the pulmonary capillaries (minimal reduction of oxygen transported until the p(O2) falls 50 mmHg).
The 'steep' portion of the oxyhemoglobin dissociation curve is the range that exists at the systemic capillaries (a small drop in systemic capillary p(O2) can result in the release of large amounts of oxygen for the metabolically active cells).
To see the relative affinities of each successive oxygen as you remove/add oxygen from/to the hemoglobin from the curve compare the relative increase/decrease in p(O2) needed for the corresponding increase/decrease in s(O2).
Factors that affect the standard dissociation curve
The strength with which oxygen binds to hemoglobin is affected by several factors. These factors shift or reshape the oxyhemoglobin dissociation curve. A shift to right indicates that the hemoglobin under study has a decreased affinity for oxygen. This makes it more difficult for hemoglobin to bind to oxygen (requiring a higher partial pressure of oxygen to achieve the same oxygen saturation), but it makes it easier for the hemoglobin to release oxygen bound to it. The effect of this shift of the curve increases the partial pressure of oxygen in the tissues when it is most needed, such as during exercise, or hemorrhagic shock.
In contrast, the curve is shifted to the left by the opposite of these conditions.
This shift indicates that the hemoglobin under study has an increased affinity for oxygen so that hemoglobin binds oxygen more easily, but unloads it more reluctantly. Left shift of the curve is a sign of hemoglobin's increased affinity for oxygen (e.g. at the lungs).
Similarly, right shift shows decreased affinity, as would appear with an increase in either body temperature, hydrogen ions, 2,3-bisphosphoglycerate (2,3-BPG) concentration or carbon dioxide concentration.
Control factors | Change | Shift of curve |
---|---|---|
Temperature | ↑ | → |
↓ | ← | |
2,3-BPG | ↑ | → |
↓ | ← | |
pCO2 | ↑ | → |
↓ | ← | |
Acidity [H+] | ↑ | → |
↓ | ← |
Note:
- Left shift: higher O2 affinity
- Right shift: lower O2 affinity
- fetal hemoglobin has higher O2 affinity than adult hemoglobin; primarily due to much-reduced affinity to 2,3-bisphosphoglycerate .
The causes of shift to right can be remembered using the mnemonic, "CADET, face Right!" for CO2, Acid, 2,3-DPG,[Note 1] Exercise and Temperature.[2] Factors that move the oxygen dissociation curve to the right are those physiological states where tissues need more oxygen. For example, during exercise, muscles have a higher metabolic rate, and consequently need more oxygen, produce more carbon dioxide and lactic acid, and their temperature rises.
pH
A decrease in pH (increase in H+ ion concentration) shifts the standard curve to the right, while an increase shifts it to the left. This occurs because at greater H+ ion concentration, various amino acid residues, such as Histidine 146 exist predominantly in their protonated form allowing them to form ion pairs that stabilize deoxyhemoglobin in the T state.[3] The T state has a lower affinity for oxygen than the R state, so with increased acidity, the hemoglobin binds less O2 for a given PO2 (and more H+). This is known as the Bohr effect.[4] A reduction in the total binding capacity of hemoglobin to oxygen (i.e. shifting the curve down, not just to the right) due to reduced pH is called the root effect. This is seen in bony fish. The binding affinity of hemoglobin to O2 is greatest under a relatively high pH.
Carbon dioxide
2,3-BPG
2,3-Bisphosphoglycerate or 2,3-BPG (formerly named 2,3-diphosphoglycerate or 2,3-DPG) is an organophosphate formed in
Temperature
Increase in temperature shifts the oxygen dissociation curve to the right. When temperature is increased keeping the oxygen concentration constant, oxygen saturation decreases as the bond between oxygen and iron gets denatured. Additionally, with increased temperature, the partial pressure of oxygen increases as well. So, one will have a lesser amount of hemoglobin saturated for the same oxygen concentration but at a higher partial pressure of oxygen. Thus, any point in the curve will shift rightwards (due to increased partial pressure of oxygen) and downwards (due to weakened bond), hence, the rightward shift of the curve.[8]
Carbon monoxide
Hemoglobin binds with
Effects of methemoglobinaemia
Effects of ITPP
Fetal hemoglobin
Fetal hemoglobin (HbF) is structurally different from normal adult hemoglobin (HbA), giving HbF a higher affinity for oxygen than HbA. HbF is composed of two alpha and two gamma chains whereas HbA is composed of two alpha and two beta chains. The fetal dissociation curve is shifted to the left relative to the curve for the normal adult because of these structural differences:
In adult hemoglobin, the binding of 2,3-bisphosphoglycerate (2,3-BPG) primarily occurs with the beta chains, preventing the binding of oxygen with haemoglobin. This binding is crucial for stabilizing the deoxygenated state of hemoglobin, promoting the efficient release of oxygen to body tissues.
In fetal hemoglobin, which possesses a gamma chain instead of a beta chain, the interaction with 2,3-BPG differes because 2,3 - -BPG not binds with gamma chain as it has lower to no affinity with gamma chain.This distinction contributes to fetal hemoglobin having a higher affinity for oxygen.
Typically, fetal arterial oxygen pressures are lower than adult arterial oxygen pressures. Hence higher affinity to bind oxygen is required at lower levels of partial pressure in the fetus to allow diffusion of oxygen across the placenta. At the placenta, there is a higher concentration of 2,3-BPG formed, and 2,3-BPG binds readily to beta chains rather than to alpha chains. As a result, 2,3-BPG binds more strongly to adult hemoglobin, causing HbA to release more oxygen for uptake by the fetus, whose HbF is unaffected by the 2,3-BPG.[10] HbF then delivers that bound oxygen to tissues that have even lower partial pressures where it can be released.
See also
- Automated analyzer
- Bohr effect
Notes
- ^ 2,3-DPG is an abbreviation of 2,3-DiPhosphoGlyceric acid, an obsolete name for 2,3-BPG
References
- ^ Ahern, Kevin; Rajagopal, Indira; Tan, Taralyn (2017). Biochemistry Free For All (PDF) (1.2 ed.). NC: Creative Commons.
- ^ "Medical mnemonics". LifeHugger. Retrieved 2009-12-19.
- ^ a b Lehninger. Principles of Biochemistry (6th ed.). p. 169.
- ^ a b c Jacquez, John (1979). Respiratory Physiology. McGraw-Hill. pp. 156–175.
- ^ Ahern, Kevin; Rajagopal, Indira; Tan, Taralyn (5 August 2017). Biochemistry Free For All (1.2 ed.). NC-Creative Commons. p. 370.
- ^ Ahern, Kevin; Rajagopal, Indira; Tan, Taralyn (5 August 2017). Biochemistry Free For All (1.2 ed.). NC-Creative Commons. p. 134.
- ISBN 978-1-4557-4214-1.
- ISBN 0521570980.
- ISBN 978-1133420071. Retrieved 2015-07-01.
- ISBN 978-0-7817-6960-0.
External links
- Nosek, Thomas M. "Section 4/4ch5/s4ch5_18". Essentials of Human Physiology. Archived from the original on 2016-03-24.
- The Interactive Oxyhemoglobin Dissociation Curve
- Simulation of the parameters CO2, pH and temperature on the oxygen–hemoglobin dissociation curve (left or right shift)