Hemoglobin
Hemoglobin | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
(heterotetramer, (αβ)2) | |||||||||||||
Protein type | metalloprotein, chromoprotein, globulin | ||||||||||||
Function | oxygen-transport | ||||||||||||
Cofactor(s) | heme (4) | ||||||||||||
|
Hemoglobin (haemoglobin,
In
Hemoglobin also transports other gases. It carries off some of the body's respiratory
Hemoglobin is also found in other cells, including in the
Hemoglobin and hemoglobin-like molecules are also found in many invertebrates, fungi, and plants.[14] In these organisms, hemoglobins may carry oxygen, or they may transport and regulate other small molecules and ions such as carbon dioxide, nitric oxide, hydrogen sulfide and sulfide. A variant called leghemoglobin serves to scavenge oxygen away from anaerobic systems such as the nitrogen-fixing nodules of leguminous plants, preventing oxygen poisoning.
The medical condition hemoglobinemia, a form of anemia, is caused by intravascular hemolysis, in which hemoglobin leaks from red blood cells into the blood plasma.
Research history
In 1825, Johann Friedrich Engelhart discovered that the ratio of iron to protein is identical in the hemoglobins of several species.[16][17] From the known atomic mass of iron, he calculated the molecular mass of hemoglobin to n × 16000 (n = number of iron atoms per hemoglobin molecule, now known to be 4), the first determination of a protein's molecular mass. This "hasty conclusion" drew ridicule from colleagues who could not believe that any molecule could be so large. However, Gilbert Smithson Adair confirmed Engelhart's results in 1925 by measuring the osmotic pressure of hemoglobin solutions.[18]
Although blood had been known to carry oxygen since at least 1794,[19][20] the oxygen-carrying property of hemoglobin was described by Hünefeld in 1840.[21] In 1851, German physiologist Otto Funke published a series of articles in which he described growing hemoglobin crystals by successively diluting red blood cells with a solvent such as pure water, alcohol or ether, followed by slow evaporation of the solvent from the resulting protein solution.[22][23] Hemoglobin's reversible oxygenation was described a few years later by Felix Hoppe-Seyler.[24]
With the development of X-ray crystallography, it became possible to sequence protein structures.[25] In 1959, Max Perutz determined the molecular structure of hemoglobin.[26][27] For this work he shared the 1962 Nobel Prize in Chemistry with John Kendrew, who sequenced the globular protein myoglobin.[25][28]
The role of hemoglobin in the blood was elucidated by French
Genetics
Hemoglobin consists of
There is more than one hemoglobin gene. In humans,
Variations in hemoglobin sequences, as with other proteins, may be adaptive. For example, hemoglobin has been found to adapt in different ways to the thin air at high altitudes, where lower partial pressure of oxygen diminishes its binding to hemoglobin compared to the higher pressures at sea level. Recent studies of deer mice found mutations in four genes that can account for differences between high- and low-elevation populations. It was found that the genes of the two breeds are "virtually identical—except for those that govern the oxygen-carrying capacity of their hemoglobin. . . . The genetic difference enables highland mice to make more efficient use of their oxygen."[36] Mammoth hemoglobin featured mutations that allowed for oxygen delivery at lower temperatures, thus enabling mammoths to migrate to higher latitudes during the Pleistocene.[37] This was also found in hummingbirds that inhabit the Andes. Hummingbirds already expend a lot of energy and thus have high oxygen demands and yet Andean hummingbirds have been found to thrive in high altitudes. Non-synonymous mutations in the hemoglobin gene of multiple species living at high elevations (Oreotrochilus, A. castelnaudii, C. violifer, P. gigas, and A. viridicuada) have caused the protein to have less of an affinity for inositol hexaphosphate (IHP), a molecule found in birds that has a similar role as 2,3-BPG in humans; this results in the ability to bind oxygen in lower partial pressures.[38]
Birds' unique circulatory lungs also promote efficient use of oxygen at low partial pressures of O2. These two adaptations reinforce each other and account for birds' remarkable high-altitude performance.[citation needed]
Hemoglobin adaptation extends to humans, as well. There is a higher offspring survival rate among Tibetan women with high oxygen saturation genotypes residing at 4,000 m.[39] Natural selection seems to be the main force working on this gene because the mortality rate of offspring is significantly lower for women with higher hemoglobin-oxygen affinity when compared to the mortality rate of offspring from women with low hemoglobin-oxygen affinity. While the exact genotype and mechanism by which this occurs is not yet clear, selection is acting on these women's ability to bind oxygen in low partial pressures, which overall allows them to better sustain crucial metabolic processes.[citation needed]
Synthesis
Hemoglobin (Hb) is synthesized in a complex series of steps. The heme part is synthesized in a series of steps in the
Structure of heme
Hemoglobin has a
In most vertebrates, the hemoglobin
A heme group consists of an iron (Fe)
Even though carbon dioxide is carried by hemoglobin, it does not compete with oxygen for the iron-binding positions but is bound to the amine groups of the protein chains attached to the heme groups.
The iron ion may be either in the
In adult humans, the most common hemoglobin type is a
In human infants, the fetal hemoglobin molecule is made up of 2 α chains and 2 γ chains. The γ chains are gradually replaced by β chains as the infant grows.[52]
The four
Oxygen saturation
In general, hemoglobin can be saturated with oxygen molecules (oxyhemoglobin), or desaturated with oxygen molecules (deoxyhemoglobin).[53]
Oxyhemoglobin
Oxyhemoglobin is formed during
Hemoglobin exists in two forms, a taut (tense) form (T) and a relaxed form (R). Various factors such as low pH, high CO2 and high
Classically, the iron in oxyhemoglobin is seen as existing in the iron(II) oxidation state. However, the complex of oxygen with heme iron is
Deoxygenated hemoglobin
Deoxygenated hemoglobin (deoxyhemoglobin) is the form of hemoglobin without the bound oxygen. The
Deoxygenated hemoglobin is
Evolution of vertebrate hemoglobin
Scientists agree that the event that separated myoglobin from hemoglobin occurred after
Most ice fish of the family Channichthyidae have lost their hemoglobin genes as an adaptation to cold water.[4]
Cooperativity
When oxygen binds to the iron complex, it causes the iron atom to move back toward the center of the plane of the porphyrin ring (see moving diagram). At the same time, the imidazole side-chain of the histidine residue interacting at the other pole of the iron is pulled toward the porphyrin ring. This interaction forces the plane of the ring sideways toward the outside of the tetramer, and also induces a strain in the protein helix containing the histidine as it moves nearer to the iron atom. This strain is transmitted to the remaining three monomers in the tetramer, where it induces a similar conformational change in the other heme sites such that binding of oxygen to these sites becomes easier.
As oxygen binds to one monomer of hemoglobin, the tetramer's conformation shifts from the T (tense) state to the R (relaxed) state. This shift promotes the binding of oxygen to the remaining three monomers' heme groups, thus saturating the hemoglobin molecule with oxygen.[65]
In the tetrameric form of normal adult hemoglobin, the binding of oxygen is, thus, a
The dynamic mechanism of the cooperativity in hemoglobin and its relation with low-frequency resonance has been discussed.[66]
Binding of ligands other than oxygen
Besides the oxygen ligand, which binds to hemoglobin in a cooperative manner, hemoglobin ligands also include competitive inhibitors such as carbon monoxide (CO) and allosteric ligands such as carbon dioxide (CO2) and nitric oxide (NO). The carbon dioxide is bound to amino groups of the globin proteins to form carbaminohemoglobin; this mechanism is thought to account for about 10% of carbon dioxide transport in mammals. Nitric oxide can also be transported by hemoglobin; it is bound to specific thiol groups in the globin protein to form an S-nitrosothiol, which dissociates into free nitric oxide and thiol again, as the hemoglobin releases oxygen from its heme site. This nitric oxide transport to peripheral tissues is hypothesized to assist oxygen transport in tissues, by releasing vasodilatory nitric oxide to tissues in which oxygen levels are low.[67]
Competitive
The binding of oxygen is affected by molecules such as carbon monoxide (for example, from tobacco smoking, exhaust gas, and incomplete combustion in furnaces). CO competes with oxygen at the heme binding site. Hemoglobin's binding affinity for CO is 250 times greater than its affinity for oxygen,[68][69] meaning that small amounts of CO dramatically reduce hemoglobin's ability to deliver oxygen to the target tissue.[70] Since carbon monoxide is a colorless, odorless and tasteless gas, and poses a potentially fatal threat, carbon monoxide detectors have become commercially available to warn of dangerous levels in residences. When hemoglobin combines with CO, it forms a very bright red compound called carboxyhemoglobin, which may cause the skin of CO poisoning victims to appear pink in death, instead of white or blue. When inspired air contains CO levels as low as 0.02%, headache and nausea occur; if the CO concentration is increased to 0.1%, unconsciousness will follow. In heavy smokers, up to 20% of the oxygen-active sites can be blocked by CO.
In similar fashion, hemoglobin also has competitive binding affinity for cyanide (CN−), sulfur monoxide (SO), and sulfide (S2−), including hydrogen sulfide (H2S). All of these bind to iron in heme without changing its oxidation state, but they nevertheless inhibit oxygen-binding, causing grave toxicity.
The iron atom in the heme group must initially be in the ferrous (Fe2+) oxidation state to support oxygen and other gases' binding and transport (it temporarily switches to ferric during the time oxygen is bound, as explained above). Initial oxidation to the ferric (Fe3+) state without oxygen converts hemoglobin into "hemiglobin" or methemoglobin, which cannot bind oxygen. Hemoglobin in normal red blood cells is protected by a reduction system to keep this from happening. Nitric oxide is capable of converting a small fraction of hemoglobin to methemoglobin in red blood cells. The latter reaction is a remnant activity of the more ancient nitric oxide dioxygenase function of globins.
Allosteric
Carbon dioxide occupies a different binding site on the hemoglobin. At tissues, where carbon dioxide concentration is higher, carbon dioxide binds to allosteric site of hemoglobin, facilitating unloading of oxygen from hemoglobin and ultimately its removal from the body after the oxygen has been released to tissues undergoing metabolism. This increased affinity for carbon dioxide by the venous blood is known as the Bohr effect. Through the enzyme carbonic anhydrase, carbon dioxide reacts with water to give carbonic acid, which decomposes into bicarbonate and protons:
- CO2 + H2O → H2CO3 → HCO3− + H+
Hence, blood with high carbon dioxide levels is also lower in pH (more acidic). Hemoglobin can bind protons and carbon dioxide, which causes a conformational change in the protein and facilitates the release of oxygen. Protons bind at various places on the protein, while carbon dioxide binds at the α-amino group.[71] Carbon dioxide binds to hemoglobin and forms carbaminohemoglobin.[72] This decrease in hemoglobin's affinity for oxygen by the binding of carbon dioxide and acid is known as the Bohr effect. The Bohr effect favors the T state rather than the R state. (shifts the O2-saturation curve to the right). Conversely, when the carbon dioxide levels in the blood decrease (i.e., in the lung capillaries), carbon dioxide and protons are released from hemoglobin, increasing the oxygen affinity of the protein. 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.
It is necessary for hemoglobin to release the oxygen that it binds; if not, there is no point in binding it. The sigmoidal curve of hemoglobin makes it efficient in binding (taking up O2 in lungs), and efficient in unloading (unloading O2 in tissues).[73]
In people acclimated to high altitudes, the concentration of
Animals other than humans use different molecules to bind to hemoglobin and change its O2 affinity under unfavorable conditions. Fish use both ATP and GTP. These bind to a phosphate "pocket" on the fish hemoglobin molecule, which stabilizes the tense state and therefore decreases oxygen affinity.[75] GTP reduces hemoglobin oxygen affinity much more than ATP, which is thought to be due to an extra hydrogen bond formed that further stabilizes the tense state.[76] Under hypoxic conditions, the concentration of both ATP and GTP is reduced in fish red blood cells to increase oxygen affinity.[77]
A variant hemoglobin, called fetal hemoglobin (HbF, α2γ2), is found in the developing fetus, and binds oxygen with greater affinity than adult hemoglobin. This means that the oxygen binding curve for fetal hemoglobin is left-shifted (i.e., a higher percentage of hemoglobin has oxygen bound to it at lower oxygen tension), in comparison to that of adult hemoglobin. As a result, fetal blood in the placenta is able to take oxygen from maternal blood.
Hemoglobin also carries
Types of hemoglobin in humans
In embryos:
- Gower 1 (ζ2ε2).
- Gower 2 (α2ε2) (PDB: 1A9W).
- Hemoglobin Portland I (ζ2γ2).
- Hemoglobin Portland II (ζ2β2).
In fetuses:
- ).
In
- Hemoglobin A (adult hemoglobin) (α2β2) (PDB: 1BZ0) – The most common with a normal amount over 95%
- Hemoglobin A2 (α2δ2) – δ chain synthesis begins late in the third trimester and, in adults, it has a normal range of 1.5–3.5%
- beta-thalassemia.
Abnormal forms that occur in diseases:
- Hemoglobin D – (α2βD2) – A variant form of hemoglobin.
- Hemoglobin H (β4) – A variant form of hemoglobin, formed by a tetramer of β chains, which may be present in variants of α thalassemia.
- Hemoglobin Barts (γ4) – A variant form of hemoglobin, formed by a tetramer of γ chains, which may be present in variants of α thalassemia.
- Hemoglobin S(α2βS2) – A variant form of hemoglobin found in people with sickle cell disease. There is a variation in the β-chain gene, causing a change in the properties of hemoglobin, which results in sickling of red blood cells.
- Hemoglobin C (α2βC2) – Another variant due to a variation in the β-chain gene. This variant causes a mild chronic hemolytic anemia.
- Hemoglobin E (α2βE2) – Another variant due to a variation in the β-chain gene. This variant causes a mild chronic hemolytic anemia.
- Hemoglobin AS – A heterozygous form causing sickle cell trait with one adult gene and one sickle cell disease gene
- Hemoglobin SC disease – A compound heterozygous form with one sickle gene and another encoding Hemoglobin C.
- Hemoglobin Sto produce sickle cell disease.
Degradation in vertebrate animals
When
The other major final product of heme degradation is bilirubin. Increased levels of this chemical are detected in the blood if red blood cells are being destroyed more rapidly than usual. Improperly degraded hemoglobin protein or hemoglobin that has been released from the blood cells too rapidly can clog small blood vessels, especially the delicate blood filtering vessels of the kidneys, causing kidney damage. Iron is removed from heme and salvaged for later use, it is stored as hemosiderin or ferritin in tissues and transported in plasma by beta globulins as transferrins. When the porphyrin ring is broken up, the fragments are normally secreted as a yellow pigment called bilirubin, which is secreted into the intestines as bile. Intestines metabolise bilirubin into urobilinogen. Urobilinogen leaves the body in faeces, in a pigment called stercobilin. Globulin is metabolised into amino acids that are then released into circulation.
Hemoglobin deficiency can be caused either by a decreased amount of hemoglobin molecules, as in
Other common causes of low hemoglobin include loss of blood, nutritional deficiency, bone marrow problems, chemotherapy, kidney failure, or abnormal hemoglobin (such as that of sickle-cell disease).
The ability of each hemoglobin molecule to carry oxygen is normally modified by altered blood pH or CO2, causing an altered oxygen–hemoglobin dissociation curve. However, it can also be pathologically altered in, e.g., carbon monoxide poisoning.
Decrease of hemoglobin, with or without an absolute decrease of red blood cells, leads to symptoms of anemia. Anemia has many different causes, although
Some mutations in the globin chain are associated with the hemoglobinopathies, such as sickle-cell disease and thalassemia. Other mutations, as discussed at the beginning of the article, are benign and are referred to merely as hemoglobin variants.
There is a group of genetic disorders, known as the
To a small extent, hemoglobin A slowly combines with
Elevated levels of hemoglobin are associated with increased numbers or sizes of red blood cells, called
A recent study done in Pondicherry, India, shows its importance in coronary artery disease.[91]
Diagnostic uses
Hemoglobin concentration measurement is among the most commonly performed
- Men: 13.8 to 18.0 g/dL (138 to 180 g/L, or 8.56 to 11.17 mmol/L)
- Women: 12.1 to 15.1 g/dL (121 to 151 g/L, or 7.51 to 9.37 mmol/L)
- Children: 11 to 16 g/dL (110 to 160 g/L, or 6.83 to 9.93 mmol/L)
- Pregnant women: 11 to 14 g/dL (110 to 140 g/L, or 6.83 to 8.69 mmol/L) (9.5 to 15 usual value during pregnancy)[94][95]
Normal values of hemoglobin in the 1st and 3rd trimesters of pregnant women must be at least 11 g/dL and at least 10.5 g/dL during the 2nd trimester.[96]
Dehydration or hyperhydration can greatly influence measured hemoglobin levels. Albumin can indicate hydration status.
If the concentration is below normal, this is called anemia. Anemias are classified by the size of red blood cells, the cells that contain hemoglobin in vertebrates. The anemia is called "microcytic" if red cells are small, "macrocytic" if they are large, and "normocytic" otherwise.
Hematocrit, the proportion of blood volume occupied by red blood cells, is typically about three times the hemoglobin concentration measured in g/dL. For example, if the hemoglobin is measured at 17 g/dL, that compares with a hematocrit of 51%.[97]
Laboratory hemoglobin test methods require a blood sample (arterial, venous, or capillary) and analysis on hematology analyzer and CO-oximeter. Additionally, a new noninvasive hemoglobin (SpHb) test method called Pulse CO-Oximetry is also available with comparable accuracy to invasive methods.[98]
Concentrations of oxy- and deoxyhemoglobin can be measured continuously, regionally and noninvasively using NIRS.[99][100][101][102][103] NIRS can be used both on the head and on muscles. This technique is often used for research in e.g. elite sports training, ergonomics, rehabilitation, patient monitoring, neonatal research, functional brain monitoring, brain–computer interface, urology (bladder contraction), neurology (Neurovascular coupling) and more.
Hemoglobin mass can be measured in humans using the non-radioactive, carbon monoxide (CO) rebreathing technique that has been used for more than 100 years. With this technique, a small volume of pure CO gas is inhaled and rebreathed for a few minutes. During rebreathing, CO binds to hemoglobin present in red blood cells. Based on the increase in blood CO after the rebreathing period, the hemoglobin mass can be determined through the dilution principle. Although CO gas in large volumes is toxic to humans, the volume of CO used to assess blood volumes corresponds to what would be inhaled when smoking a cigarette. While researchers typically use custom-made rebreathing circuits, the Detalo Performance from Detalo Health has automated the procedure and made the measurement available to a larger group of users.[104]
Long-term control of
The
Athletic tracking and self tracking uses
Hemoglobin can be tracked noninvasively, to build an individual data set tracking the hemoconcentration and hemodilution effects of daily activities for better understanding of sports performance and training. Athletes are often concerned about endurance and intensity of exercise. The sensor uses light-emitting diodes that emit red and infrared light through the tissue to a light detector, which then sends a signal to a processor to calculate the absorption of light by the hemoglobin protein.[107] This sensor is similar to a
Analogues in non-vertebrate organisms
A variety of oxygen-transport and -binding proteins exist in organisms throughout the animal and plant kingdoms. Organisms including
The structure of hemoglobins varies across species. Hemoglobin occurs in all kingdoms of organisms, but not in all organisms. Primitive species such as bacteria, protozoa,
One of the most striking occurrences and uses of hemoglobin in organisms is in the
Other oxygen-binding proteins
- Myoglobin
- Found in the muscle tissue of many vertebrates, including humans, it gives muscle tissue a distinct red or dark gray color. It is very similar to hemoglobin in structure and sequence, but is not a tetramer; instead, it is a monomer that lacks cooperative binding. It is used to store oxygen rather than transport it.
- Hemocyanin
- The second most common oxygen-transporting protein found in nature, it is found in the blood of many arthropods and molluscs. Uses copper prosthetic groups instead of iron heme groups and is blue in color when oxygenated.
- Hemerythrin
- Some marine invertebrates and a few species of annelid use this iron-containing non-heme protein to carry oxygen in their blood. Appears pink/violet when oxygenated, clear when not.
- Chlorocruorin
- Found in many annelids, it is very similar to erythrocruorin, but the heme group is significantly different in structure. Appears green when deoxygenated and red when oxygenated.
- Vanabins
- Also known as sea squirts. They were once hypothesized to use the metal vanadium as an oxygen binding prosthetic group. However, although they do contain vanadium by preference, they apparently bind little oxygen, and thus have some other function, which has not been elucidated (sea squirts also contain some hemoglobin). They may act as toxins.
- Erythrocruorin
- Found in many annelids, including earthworms, it is a giant free-floating blood protein containing many dozens—possibly hundreds—of iron- and heme-bearing protein subunits bound together into a single protein complex with a molecular mass greater than 3.5 million daltons.
- Leghemoglobin
- In leguminous plants, such as alfalfa or soybeans, the nitrogen fixing bacteria in the roots are protected from oxygen by this iron heme containing oxygen-binding protein. The specific enzyme protected is nitrogenase, which is unable to reduce nitrogen gas in the presence of free oxygen.
- Coboglobin
- A synthetic cobalt-based porphyrin. Coboprotein would appear colorless when oxygenated, but yellow when in veins.
Presence in nonerythroid cells
Some nonerythroid cells (i.e., cells other than the red blood cell line) contain hemoglobin. In the brain, these include the A9 dopaminergic neurons in the substantia nigra, astrocytes in the cerebral cortex and hippocampus, and in all mature oligodendrocytes.[12] It has been suggested that brain hemoglobin in these cells may enable the "storage of oxygen to provide a homeostatic mechanism in anoxic conditions, which is especially important for A9 DA neurons that have an elevated metabolism with a high requirement for energy production".[12] It has been noted further that "A9 dopaminergic neurons may be at particular risk of anoxic degeneration since in addition to their high mitochondrial activity they are under intense oxidative stress caused by the production of hydrogen peroxide via autoxidation and/or monoamine oxidase (MAO)-mediated deamination of dopamine and the subsequent reaction of accessible ferrous iron to generate highly toxic hydroxyl radicals".[12] This may explain the risk of degeneration of these cells in Parkinson's disease.[12] The hemoglobin-derived iron in these cells is not the cause of the post-mortem darkness of these cells (origin of the Latin name, substantia nigra), but rather is due to neuromelanin.
Outside the brain, hemoglobin has non-oxygen-carrying functions as an
In history, art and music
Historically, an association between the color of blood and rust occurs in the association of the planet Mars, with the Roman god of war, since the planet is an orange-red, which reminded the ancients of blood. Although the color of the planet is due to iron compounds in combination with oxygen in the Martian soil, it is a common misconception that the iron in hemoglobin and its oxides gives blood its red color. The color is actually due to the porphyrin moiety of hemoglobin to which the iron is bound, not the iron itself,[114] although the ligation and redox state of the iron can influence the pi to pi* or n to pi* electronic transitions of the porphyrin and hence its optical characteristics.
Artist Julian Voss-Andreae created a sculpture called Heart of Steel (Hemoglobin) in 2005, based on the protein's backbone. The sculpture was made from glass and weathering steel. The intentional rusting of the initially shiny work of art mirrors hemoglobin's fundamental chemical reaction of oxygen binding to iron.[115][116]
Montreal artist Nicolas Baier created Lustre (Hémoglobine), a sculpture in stainless steel that shows the structure of the hemoglobin molecule. It is displayed in the atrium of McGill University Health Centre's research centre in Montreal. The sculpture measures about 10 metres × 10 metres × 10 metres.[117][118]
See also
- Carbaminohemoglobin (Hb associated with CO2)
- Carboxyhemoglobin (Hb associated with CO)
- Chlorophyll (Mg heme)
- Complete blood count
- Delta globin
- Hemoglobinometer
- Hemoprotein
- Methemoglobin (ferric Hb, or ferrihemoglobin)
- Oxyhemoglobin (with diatomic oxygen, colored blood-red)
- Vaska's complex – iridium organometallic complex notable for its ability to bind to O2 reversibly
- Tegillarca granosa
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Notes
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- ISBN 978-0-443-07202-4.[page needed]
- ^ "Hemoglobin Variants". Lab Tests Online. American Association for Clinical Chemistry. 2007-11-10. Archived from the original on 2008-09-20. Retrieved 2008-10-12.
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- ^ "hemoglobinopathy" at Dorland's Medical Dictionary
- ^ hypoxemia Archived 2009-02-02 at the Wayback Machine. Encyclopædia Britannica, stating hypoxemia (reduced oxygen tension in the blood).
- ^ Biology-Online.org --> Dictionary » H » Hypoxemia Archived 2009-11-21 at the Wayback Machine last modified 29 December 2008
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- ^ "NGSP: HbA1c and eAG". www.ngsp.org. Archived from the original on 2015-10-15. Retrieved 2015-10-28.
- ^ "Definition of Glycosylated Hemoglobin." Archived 2014-01-23 at the Wayback Machine Medicine Net. Web. 12 Oct. 2009.
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- ^ Hemoglobin Archived 2016-06-10 at the Wayback Machine at Medline Plus
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- ^ Hemoglobin Level Test Archived 2007-01-29 at the Wayback Machine. Ibdcrohns.about.com (2013-08-16). Retrieved 2013-09-05.
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- ^ This Hb A1c level is only useful in individuals who have red blood cells (RBCs) with normal survivals (i.e., normal half-life). In individuals with abnormal RBCs, whether due to abnormal hemoglobin molecules (such as Hemoglobin S in Sickle Cell Anemia) or RBC membrane defects – or other problems, the RBC half-life is frequently shortened. In these individuals, an alternative test called "fructosamine level" can be used. It measures the degree of glycation (glucose binding) to albumin, the most common blood protein, and reflects average blood glucose levels over the previous 18–21 days, which is the half-life of albumin molecules in the circulation.
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- ^ "Cercacor – How Ember's non-invasive hemoglobin technology works". technology.cercacor.com. Archived from the original on 2016-11-04. Retrieved 2016-11-03.
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- ^ Henry, Sean (August 7, 2014). "Take a sneak peek at the MUHC's art collection". CBC News. Archived from the original on February 5, 2016. Retrieved February 1, 2016.
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Further reading
- Campbell, MK (1999). Biochemistry (third ed.). Harcourt. ISBN 978-0-03-024426-1.
- Eshaghian, S; Horwich, TB; Fonarow, GC (2006). "An unexpected inverse relationship between HbA1c levels and mortality in patients with diabetes and advanced systolic heart failure". Am Heart J. 151 (1): 91.e1–91.e6. PMID 16368297.
- Ganong, WF (2003). Review of Medical Physiology (21st ed.). Lange. ISBN 978-0-07-140236-1.
- Hager, T (1995). Force of Nature: The Life of Linus Pauling. Simon and Schuster. ISBN 978-0-684-80909-0.
- Hazelwood, Loren (2001) Can't Live Without It: The story of hemoglobin in sickness and in health, ISBN 1-56072-907-4
- Kneipp J, Balakrishnan G, Chen R, Shen TJ, Sahu SC, Ho NT, Giovannelli JL, Simplaceanu V, Ho C, Spiro T (2005). "Dynamics of allostery in hemoglobin: roles of the penultimate tyrosine H bonds". J Mol Biol. 356 (2): 335–53. PMID 16368110.
- Hardison, Ross C. (2012). "Evolution of Hemoglobin and Its Genes". Cold Spring Harbor Perspectives in Medicine. 2 (12): a011627. PMID 23209182.
External links
- Proteopedia Hemoglobin
- National Anemia Action Council at anemia.org
- New hemoglobin type causes mock diagnosis with pulse oxymeters Archived 2016-03-09 at the Wayback Machine at www.life-of-science.net Archived 2017-03-07 at the Wayback Machine
- Animation of hemoglobin: from deoxy to oxy form at vimeo.com