Hemoglobin - Knowledge

1093:. This separation of myoglobin and hemoglobin allowed for the different functions of the two molecules to arise and develop: myoglobin has more to do with oxygen storage while hemoglobin is tasked with oxygen transport. The α- and β-like globin genes encode the individual subunits of the protein. The predecessors of these genes arose through another duplication event also after the gnathosome common ancestor derived from jawless fish, approximately 450–500 million years ago. Ancestral reconstruction studies suggest that the preduplication ancestor of the α and β genes was a dimer made up of identical globin subunits, which then evolved to assemble into a tetrameric architecture after the duplication. The development of α and β genes created the potential for hemoglobin to be composed of multiple distinct subunits, a physical composition central to hemoglobin's ability to transport oxygen. Having multiple subunits contributes to hemoglobin's ability to bind oxygen cooperatively as well as be regulated allosterically. Subsequently, the α gene also underwent a duplication event to form the 2022:

T2DM results in high levels of glycated hemoglobin in the red blood cells. The normal reference range is approximately 4.0–5.9%. Though difficult to obtain, values less than 7% are recommended for people with T2DM. Levels greater than 9% are associated with poor control of the glycated hemoglobin, and levels greater than 12% are associated with very poor control. Diabetics who keep their glycated hemoglobin levels close to 7% have a much better chance of avoiding the complications that may accompany diabetes (than those whose levels are 8% or higher). In addition, increased glycated of hemoglobin increases its affinity for oxygen, therefore preventing its release at the tissue and inducing a level of hypoxia in extreme cases.

2067: 2282: 1514:(NO) in the globin part of the molecule. This improves oxygen delivery in the periphery and contributes to the control of respiration. NO binds reversibly to a specific cysteine residue in globin; the binding depends on the state (R or T) of the hemoglobin. The resulting S-nitrosylated hemoglobin influences various NO-related activities such as the control of vascular resistance, blood pressure and respiration. NO is not released in the cytoplasm of red blood cells but transported out of them by an anion exchanger called 2565: 2159:

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.

1399: 1717: 2633: 62: 661: 1859:, which is exclusively expressed on monocytes or macrophages. Within these cells the hemoglobin molecule is broken up, and the iron gets recycled. This process also produces one molecule of carbon monoxide for every molecule of heme degraded. Heme degradation is the only natural source of carbon monoxide in the human body, and is responsible for the normal blood levels of carbon monoxide in people breathing normal air. 2647: 769: 708:

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.

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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."

856:, completing the octahedral group of six ligands. This reversible bonding with oxygen is why hemoglobin is so useful for transporting oxygen around the body. Oxygen binds in an "end-on bent" geometry where one oxygen atom binds to Fe and the other protrudes at an angle. When oxygen is not bound, a very weakly bonded water molecule fills the site, forming a distorted 1878:. 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 metabolize bilirubin into urobilinogen. Urobilinogen leaves the body in faeces, in a pigment called stercobilin. Globulin is metabolized into amino acids that are then released into circulation. 1434:). 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 2855:

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.

787:, and these helices are connected by short non-helical segments. Hydrogen bonds stabilize the helical sections inside this protein, causing attractions within the molecule, which then causes each polypeptide chain to fold into a specific shape. Hemoglobin's quaternary structure comes from its four subunits in roughly a tetrahedral arrangement. 2583:, 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 2444:. 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. 1866:. 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 2516:. 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". It has been noted further that "A9 2254:(iron in a flat porphyrin support), they are often called hemoglobins, even if their overall tertiary structure is very different from that of vertebrate hemoglobin. In particular, the distinction of "myoglobin" and hemoglobin in lower animals is often impossible, because some of these organisms do not contain 681:. 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 ( 1503:, 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 2021:

percentage reflects a weighted average of blood glucose levels over the lifetime of red cells, which is approximately 120 days. The levels of glycated hemoglobin are therefore measured in order to monitor the long-term control of the chronic disease of type 2 diabetes mellitus (T2DM). Poor control of

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conformational changes of the hemoglobin protein complex as discussed above; i.e., when one subunit protein in hemoglobin becomes oxygenated, a conformational or structural change in the whole complex is initiated, causing the other subunits to gain an increased affinity for oxygen. As a consequence,

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on chromosome 11. The amino acid sequences of the globin subunits usually differ between species, with the difference growing with evolutionary distance. For example, the most common hemoglobin sequences in humans, bonobos and chimpanzees are completely identical, with exactly the same alpha and beta

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for use as synthetic raw material similar to photosynthetic plants. The structures are bright red due to their content of several extraordinarily complex hemoglobins that have up to 144 globin chains, each including associated heme structures. These hemoglobins are remarkable for being able to carry

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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.

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oxide 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

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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

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affinity where, at high partial pressures of oxygen (such as those present in the alveoli), the relaxed (high affinity, R) state is favoured. Inversely, at low partial pressures (such as those present in respiring tissues), the (low affinity, T) tense state is favoured. Additionally, the binding of

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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. Natural selection seems to be the main force working on this gene because the mortality rate of offspring is significantly lower

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Hemoglobin and hemoglobin-like molecules are also found in many invertebrates, fungi, and plants. 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

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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

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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

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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

1327:, 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 468:

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. Hemoglobin's reversible oxygenation was

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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

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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.

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allosteric effect. Hemoglobin in organisms at high altitudes has also adapted such that it has less of an affinity for 2,3-BPG and so the protein will be shifted more towards its R state. In its R state, hemoglobin will bind oxygen more readily, thus allowing organisms to perform the necessary

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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

1176:. The binding affinity of hemoglobin for oxygen is increased by the oxygen saturation of the molecule, with the first molecules of oxygen bound influencing the shape of the binding sites for the next ones, in a way favorable for binding. This positive cooperative binding is achieved through 2005:. The binding of glucose to amino acids in the hemoglobin takes place spontaneously (without the help of an enzyme) in many proteins, and is not known to serve a useful purpose. However, as the concentration of glucose in the blood increases, the percentage of Hb A that turns into Hb A 1244:

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

1144:. For example, in the upper-left of the four hemes shown, oxygen binds at the left of the iron atom shown in the upper-left of diagram. This causes the iron atom to move backward into the heme that holds it (the iron moves upward as it binds oxygen, in this illustration), tugging the 2133:

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.

1265:, 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, Since carbon monoxide is a colorless, odorless and tasteless gas, and poses a potentially fatal threat, 1418:). 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. Carbon dioxide binds to hemoglobin and forms 431: 1168:

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.

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oxygen to the iron(II) heme pulls the iron into the plane of the porphyrin ring, causing a slight conformational shift. The shift encourages oxygen to bind to the three remaining heme units within hemoglobin (thus, oxygen binding is cooperative).

457:=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, 1480:. These bind to a phosphate "pocket" on the fish hemoglobin molecule, which stabilizes the tense state and therefore decreases oxygen affinity. GTP reduces hemoglobin oxygen affinity much more than ATP, which is thought to be due to an extra 2270:). In all these groups, heme/globin-containing molecules (even monomeric globin ones) that deal with gas-binding are referred to as oxyhemoglobins. In addition to dealing with transport and sensing of oxygen, they may also deal with NO, CO 2106:/L. 1 g/dL equals about 0.6206 mmol/L, although the latter units are not used as often due to uncertainty regarding the polymeric state of the molecule. This conversion factor, using the single globin unit molecular weight of 16,000 2140:, 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%. 2458:, 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. 2590:

of hemoglobin to which the iron is bound, not the iron itself, 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.

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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. This sensor is similar to a

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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.

2151:. 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, 448:

In 1825, Johann Friedrich Engelhart discovered that the ratio of iron to protein is identical in the hemoglobins of several species. From the known atomic mass of iron, he calculated the molecular mass of hemoglobin to

2110:, is more common for hemoglobin concentration in blood. For MCHC (mean corpuscular hemoglobin concentration) the conversion factor 0.155, which uses the tetramer weight of 64,500 Da, is more common. Normal levels are: 882:

ion, thus iron must exist in the +2 oxidation state to bind oxygen. If superoxide ion associated to Fe is protonated, the hemoglobin iron will remain oxidized and incapable of binding oxygen. In such cases, the enzyme

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Rutjes, H. A.; Nieveen, M. C.; Weber, R. E.; Witte, F.; Van den Thillart, G. E. E. J. M. (20 June 2007). "Multiple strategies of Lake Victoria cichlids to cope with lifelong hypoxia include hemoglobin switching".

1782:) – 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. 5205:

Pillai, Arvind S.; Chandler, Shane A.; Liu, Yang; Signore, Anthony V.; Cortez-Romero, Carlos R.; Benesch, Justin L. P.; Laganowsky, Arthur; Storz, Jay F.; Hochberg, Georg K. A.; Thornton, Joseph W. (May 2020).

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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

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Perutz, M.F.; Rossmann, M.G.; Cullis, A.F.; Muirhead, H.; Will, G.; North, A.C.T. (1960). "Structure of haemoglobin: a three-dimensional Fourier synthesis at 5.5-A. resolution, obtained by X-ray analysis".

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Letters from Dr. Withering, ... Dr. Ewart, ... Dr. Thorton ... and Dr. Biggs ... together with some other papers, supplementary to two publications on asthma, consumption, fever, and other diseases, by T.

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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

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Considerations on the Medicinal Use, and on the Production of Factitious Airs: Part I. By Thomas Beddoes, M.D. Part II. By James Watt, Engineer; "Part 1, section 2, "Of the breathing of man and familiar

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It is important to note that in the setting of carboxyhemoglobinemia, it is not a reduction in oxygen-carrying capacity that causes pathology, but an impaired delivery of bound oxygen to target tissues.

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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.

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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).

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reach the end of their life due to aging or defects, they are removed from the circulation by the phagocytic activity of macrophages in the spleen or the liver or hemolyze within the circulation.

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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".

6577:"Simultaneous measurements of cerebral oxygenation changes during brain activation by near-infrared spectroscopy and functional magnetic resonance imaging in healthy young and elderly subjects" 1050:

than deoxyhemoglobin, while at 940 nm its absorption is slightly higher. This difference is used for the measurement of the amount of oxygen in a patient's blood by an instrument called a

1315:(Fe) 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 1101:

genes. These further duplications and divergences have created a diverse range of α- and β-like globin genes that are regulated so that certain forms occur at different stages of development.

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group. Each heme group contains one iron atom, that can bind one oxygen molecule through ion-induced dipole forces. The most common type of hemoglobin in mammals contains four such subunits.

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Projecto-Garcia, Joana; Natarajan, Chandrasekhar; Moriyama, Hideaki; Weber, Roy E.; Fago, Angela; Cheviron, Zachary A.; Dudley, Robert; McGuire, Jimmy A.; Witt, Christopher C. (2013-12-17).

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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 O

6713:"The multi-hemoglobin system of the hydrothermal vent tube worm Riftia pachyptila. II. Complete polypeptide chain composition investigated by maximum entropy analysis of mass spectra" 6286:

Frasca, D.; Dahyot-Fizelier, C.; Catherine, K.; Levrat, Q.; Debaene, B.; Mimoz, O. (2011). "Accuracy of a continuous noninvasive hemoglobin monitor in intensive care unit patients*".

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scavenging in environments that must be anaerobic. They may even deal with detoxification of chlorinated materials in a way analogous to heme-containing P450 enzymes and peroxidases.

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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".

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Gronenborn, Angela M.; Clore, G.Marius; Brunori, Maurizio; Giardina, Bruno; Falcioni, Giancarlo; Perutz, Max F. (1984). "Stereochemistry of ATP and GTP bound to fish haemoglobins".

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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.

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globin protein chains. Human and gorilla hemoglobin differ in one amino acid in both alpha and beta chains, and these differences grow larger between less closely related species.

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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.

1708:) – In adults Hemoglobin F is restricted to a limited population of red cells called F-cells. However, the level of Hb F can be elevated in persons with sickle-cell disease and 1484:

formed that further stabilizes the tense state. Under hypoxic conditions, the concentration of both ATP and GTP is reduced in fish red blood cells to increase oxygen affinity.

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Van Beekvelt MC, Colier WN, Wevers RA, Van Engelen BG (2001). "Performance of near-infrared spectroscopy in measuring local O2 consumption and blood flow in skeletal muscle".

7034: 2049:. High hemoglobin levels may also be caused by exposure to high altitudes, smoking, dehydration (artificially by concentrating Hb), advanced lung disease and certain tumors. 464:

Although blood had been known to carry oxygen since at least 1794, the oxygen-carrying property of hemoglobin was described by Hünefeld in 1840. In 1851, German physiologist

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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,

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of the tetramer of about 64,000 daltons (64,458 g/mol). Thus, 1 g/dL=0.1551 mmol/L. Hemoglobin A is the most intensively studied of the hemoglobin molecules.

4805: 7331: 4961:"Functional brain mapping by blood oxygenation level-dependent contrast magnetic resonance imaging. A comparison of signal characteristics with a biophysical model" 971:

of the lungs. The oxygen then travels through the blood stream to be dropped off at cells where it is utilized as a terminal electron acceptor in the production of

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oxygen in the presence of sulfide, and even to carry sulfide, without being completely "poisoned" or inhibited by it as hemoglobins in most other species are.

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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.

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within a single species, although one sequence is usually "most common" in each species. Many of these mutations cause no disease, but some cause a group of

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have become commercially available to warn of dangerous levels in residences. When hemoglobin combines with CO, it forms a very bright red compound called

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Decrease of hemoglobin, with or without an absolute decrease of red blood cells, leads to symptoms of anemia. Anemia has many different causes, although

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hemoglobin featured mutations that allowed for oxygen delivery at lower temperatures, thus enabling mammoths to migrate to higher latitudes during the

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seventy-fold compared to dissolved oxygen in blood plasma alone. The mammalian hemoglobin molecule can bind and transport up to four oxygen molecules.

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Sidell, Bruce; Kristin O'Brien (2006). "When bad things happen to good fish: the loss of hemoglobin and myoglobin expression in Antarctic icefishes".

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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.

693:(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. 8729: 4197: 2194:

proportion of 6.0% or less show good long-term glucose control, while values above 7.0% are elevated. This test is especially useful for diabetics.

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atoms in the center of the ring, which all lie in one plane. The heme is bound strongly (covalently) to the globular protein via the N atoms of the

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S). All of these bind to iron in heme without changing its oxidation state, but they nevertheless inhibit oxygen-binding, causing grave toxicity.

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Mehagnoul-Schipper DJ, van der Kallen BF, Colier WN, van der Sluijs MC, van Erning LJ, Thijssen HO, Oeseburg B, Hoefnagels WH, Jansen RW (2002).

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at the level of the tissues favor the taut form, which has low oxygen affinity and releases oxygen in the tissues. Conversely, a high pH, low CO

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Nishi, Hiroshi; Inagi, Reiko; Kato, Hideki; Tanemoto, Masayuki; Kojima, Ichiro; Son, Daisuke; Fujita, Toshiro; Nangaku, Masaomi (August 2008).

2525:. 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 2201:(fMRI) machine uses the signal from deoxyhemoglobin, which is sensitive to magnetic fields since it is paramagnetic. Combined measurement with 898:, consisting of two α and two β subunits non-covalently bound, each made of 141 and 146 amino acid residues, respectively. This is denoted as α 1456:(2,3-BPG) in the blood is increased, which allows these individuals to deliver a larger amount of oxygen to tissues under conditions of lower 8982: 6189: 3592: 2521:

reaction of accessible ferrous iron to generate highly toxic hydroxyl radicals". This may explain the risk of degeneration of these cells in

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Classically, the iron in oxyhemoglobin is seen as existing in the iron(II) oxidation state. However, the complex of oxygen with heme iron is

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are the most common causes in the Western world. As absence of iron decreases heme synthesis, red blood cells in iron deficiency anemia are

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Jensen, Frank B (2009). "The dual roles of red blood cells in tissue oxygen delivery: oxygen carriers and regulators of local blood flow".

3748: 2610:. The intentional rusting of the initially shiny work of art mirrors hemoglobin's fundamental chemical reaction of oxygen binding to iron. 379:

of the kidney, endometrial cells, cervical cells, and vaginal epithelial cells. In these tissues, hemoglobin absorbs unneeded oxygen as an

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Gene expression of hemoglobin before and after birth. Also identifies the types of cells and organs in which the gene expression (data on

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residue (modeled as a red pentagon on the right of the iron) closer, as it does. This, in turn, pulls on the protein chain holding the

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In general, hemoglobin can be saturated with oxygen molecules (oxyhemoglobin), or desaturated with oxygen molecules (deoxyhemoglobin).

878:) (Fe) cannot bind oxygen. In binding, oxygen temporarily and reversibly oxidizes (Fe) to (Fe) while oxygen temporarily turns into the 1026:. Experimental evidence strongly suggests heme iron is in the iron(III) oxidation state in oxyhemoglobin, with the oxygen existing as 8638: 7064: 2230:

A variety of oxygen-transport and -binding proteins exist in organisms throughout the animal and plant kingdoms. Organisms including

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McCully, K. K.; Hamaoka, T. (2000). "Near-infrared spectroscopy: What can it tell us about oxygen saturation in skeletal muscle?".

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Maton, Anthea; Jean Hopkins; Charles William McLaughlin; Susan Johnson; Maryanna Quon Warner; David LaHart; Jill D. Wright (1993).

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Some nonerythroid cells (i.e., cells other than the red blood cell line) contain hemoglobin. In the brain, these include the A9

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arrangement. Such a name is given because this arrangement is the same folding motif used in other heme/globin proteins such as

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Protein alignment of human hemoglobin proteins, alpha, beta, and delta subunits respectively. The alignments were created using

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contain very large multisubunit molecules, much larger than those in vertebrates. In particular, chimeric hemoglobins found in

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bridges) with the iron ion bound in the center. The iron ion, which is the site of oxygen binding, coordinates with the four

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proportion represents glucose level in blood averaged over the half-life of red blood cells, is typically ~120 days. An Hb A

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residue (also known as the proximal histidine) below the porphyrin ring. A sixth position can reversibly bind oxygen by a

317:(excluding water), and around 35% of the total weight (including water). Hemoglobin has an oxygen-binding capacity of 1.34 8972: 2978: 1010:, or low 2,3 BPG favors the relaxed form, which can better bind oxygen. The partial pressure of the system also affects O 5081:

Goodman, Morris; Moore, G. William; Matsuda, Genji (1975-02-20). "Darwinian evolution in the genealogy of haemoglobin".

4657: 3072:"Equality of the in vivo and in vitro oxygen-binding capacity of hemoglobin in patients with severe respiratory disease" 7822: 7677: 2617:, a sculpture in stainless steel that shows the structure of the hemoglobin molecule. It is displayed in the atrium of 2130:

Dehydration or hyperhydration can greatly influence measured hemoglobin levels. Albumin can indicate hydration status.

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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.

4065: 1768:) – A variant form of hemoglobin, formed by a tetramer of γ chains, which may be present in variants of α thalassemia. 716:

Hemoglobin (Hb) is synthesized in a complex series of steps. The heme part is synthesized in a series of steps in the

8914: 8648: 7220: 5773: 4176: 1046:

of oxyhemoglobin and deoxyhemoglobin differ. The oxyhemoglobin has significantly lower absorption of the 660 nm

8951: 4123: 4094: 2123:

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)

8875: 6655:"The hemoglobin concentration of Chironomus cf.Plumosus L. (Diptera: Chironomidae) larvae from two lentic habitats" 1984: 1156:

When oxygen binds to the iron complex, it causes the iron atom to move back toward the center of the plane of the

9058: 9043: 9010: 8571: 7371: 7089: 2618: 2483:

A synthetic cobalt-based porphyrin. Coboprotein would appear colorless when oxygenated, but yellow when in veins.

1277:

victims to appear pink in death, instead of white or blue. When inspired air contains CO levels as low as 0.02%,

963:

when oxygen binds to the heme component of the protein hemoglobin in red blood cells. This process occurs in the

1814:) – Another variant due to a variation in the β-chain gene. This variant causes a mild chronic hemolytic anemia. 649:

involves underproduction of normal and sometimes abnormal hemoglobins, through problems and mutations in globin

9053: 8777: 7741: 6248: 6177: 5563: 4881: 2921: 2170:. Measuring it directly would require many samples because blood sugar levels vary widely through the day. Hb A 1895: 6632: 3614: 2342:, these worms contain a population of bacteria constituting half the organism's weight. The bacteria oxidize H 1870:, causing kidney damage. Iron is removed from heme and salvaged for later use, it is stored as hemosiderin or 1422:. This decrease in hemoglobin's affinity for oxygen by the binding of carbon dioxide and acid is known as the 1350:

tissues undergoing metabolism. This increased affinity for carbon dioxide by the venous blood is known as the

571:

which determine the protein's chemical properties and function. The amino acid sequence of any polypeptide is

8904: 8662: 7468: 7345: 6014: 5713:

Weber, Roy E.; Frank B. Jensen (1988). "Functional adaptations in hemoglobins from ectothermic vertebrates".

4848: 2358:. The worms' upper end is a deep-red fan-like structure ("plume"), which extends into the water and absorbs H 1460:. This phenomenon, where molecule Y affects the binding of molecule X to a transport molecule Z, is called a 4632: 2242:

all have hemoglobin-like proteins whose known and predicted roles include the reversible binding of gaseous

2147:

Concentrations of oxy- and deoxyhemoglobin can be measured continuously, regionally and noninvasively using

1994:

at the terminal valine (an alpha aminoacid) of each β chain. The resulting molecule is often referred to as

8899: 7590: 3476: 2206: 2152: 1970:. Other mutations, as discussed at the beginning of the article, are benign and are referred to merely as 1694:) – δ chain synthesis begins late in the third trimester and, in adults, it has a normal range of 1.5–3.5% 704:. These two adaptations reinforce each other and account for birds' remarkable high-altitude performance. 8821: 8787: 8633: 7760: 7709: 7560: 4329:"Higher offspring survival among Tibetan women with high oxygen saturation genotypes residing at 4,000 m" 4201: 2579:

Historically, an association between the color of blood and rust occurs in the association of the planet

1530: 17: 2025:

Elevated levels of hemoglobin are associated with increased numbers or sizes of red blood cells, called

1754:) – A variant form of hemoglobin, formed by a tetramer of β chains, which may be present in variants of 8909: 8760: 7865: 7714: 5606: 3319:"Unexpected expression of alpha- and beta-globin in mesencephalic dopaminergic neurons and glial cells" 2904: 2202: 2148: 1932: 360: 3864:"John Kendrew and myoglobin: Protein structure determination in the 1950s: John Kendrew and Myoglobin" 1916:

The ability of each hemoglobin molecule to carry oxygen is normally modified by altered blood pH or CO

8870: 8667: 7622: 7553: 7534: 7322: 4262:"Repeated elevational transitions in hemoglobin function during the evolution of Andean hummingbirds" 2908: 1925: 1274: 976: 438: 7108: 760:(this hemoglobin-synthetic RNA in fact gives the reticulocyte its reticulated appearance and name). 8747: 7940: 7698: 7565: 7529: 7423: 6893:

Nishi, H.; Inagi, R.; Kato, H.; Tanemoto, M.; Kojima, I.; Son, D.; Fujita, T.; Nangaku, M. (2008).

2030: 1328: 1266: 980: 960: 853: 783:

characteristic of many multi-subunit globular proteins. Most of the amino acids in hemoglobin form

485: 6197: 4731: 3585: 3410:

Weber RE, Vinogradov SN (2001). "Nonvertebrate hemoglobins: functions and molecular adaptations".

2841:

Although other sources can have slightly differing values, such as UK's General Practice Notebook.

1890:, or by decreased ability of each molecule to bind oxygen at the same partial pressure of oxygen. 1402:

The sigmoidal shape of hemoglobin's oxygen-dissociation curve results from cooperative binding of

1042:

Deoxygenated hemoglobin (deoxyhemoglobin) is the form of hemoglobin without the bound oxygen. The

8831: 8643: 8018: 7962: 7731: 7600: 7213: 4959:

Ogawa, S; Menon, R. S.; Tank, D. W.; Kim, S. G.; Merkle, H; Ellermann, J. M.; Ugurbil, K (1993).

4030:"Using the NCBI Genome Databases to Compare the Genes for Human & Chimpanzee Beta Hemoglobin" 1534: 1453: 884: 732:

in the cytosol. Production of Hb continues in the cell throughout its early development from the

461:

confirmed Engelhart's results in 1925 by measuring the osmotic pressure of hemoglobin solutions.

415: 387:. Excessive glucose in the blood can attach to hemoglobin and raise the level of hemoglobin A1c. 7999: 6054:

Madsen, H; Ditzel, J (1984). "Blood-oxygen transport in first trimester of diabetic pregnancy".

6034: 5139:"Gene duplication, genome duplication, and the functional diversification of vertebrate globins" 3643: 2621:'s research centre in Montreal. The sculpture measures about 10 metres × 10 metres × 10 metres. 1886:

Hemoglobin deficiency can be caused either by a decreased amount of hemoglobin molecules, as in

8765: 8657: 8628: 7548: 7495: 7485: 7394: 6456:

Perrey, S. P. (2008). "Non-invasive NIR spectroscopy of human brain function during exercise".

6261: 2522: 1936: 1824:

Hemoglobin SC disease – A compound heterozygous form with one sickle gene and another encoding

1796:) – Another variant due to a variation in the β-chain gene. This variant causes a mild chronic 1477: 1473: 1213: 972: 458: 5926: 5878: 4497: 8962: 8941: 7858: 7736: 7672: 2175: 1236:; this mechanism is thought to account for about 10% of carbon dioxide transport in mammals. 1221: 1209: 1196:

The dynamic mechanism of the cooperativity in hemoglobin and its relation with low-frequency

964: 929: 825: 572: 477: 326: 7850: 6226: 5837:

Coomes, Marguerite W. (2011). "Amino Acid and Heme Metabolism". In Devlin, Thomas M. (ed.).

4613: 2052:

A recent study done in Pondicherry, India, shows its importance in coronary artery disease.

798:

subunits. Each subunit is composed of a protein chain tightly associated with a non-protein

756:

allows further synthesis of Hb until the reticulocyte loses its RNA soon after entering the

9048: 8892: 8858: 8679: 8605: 8143: 8129: 8115: 8101: 7791: 7646: 7610: 7445: 7440: 6806: 6666: 6342: 5359: 5292: 5219: 5150: 5090: 5032: 4972: 4568: 4340: 4273: 3793: 3556: 3332: 2682: 2083: 1955:

is caused by the hemoglobin metabolite bilirubin, and the circulating hemoglobin can cause

1831: 780: 211: 193: 175: 7056: 4116:"HBA1 – Hemoglobin subunit alpha – Pan troglodytes (Chimpanzee) – HBA1 gene & protein" 4087:"HBB – Hemoglobin subunit beta – Pan paniscus (Pygmy chimpanzee) – HBB gene & protein" 1257:

The binding of oxygen is affected by molecules such as carbon monoxide (for example, from

8: 8887: 8742: 8409: 8379: 8303: 7945: 7473: 5677: 5021:"Discovery of the magnetic behavior of hemoglobin: A beginning of bioinorganic chemistry" 4235: 2660: 2595: 2572: 2380: 2070:

A hemoglobin concentration measurement being administered before a blood donation at the

2002: 1971: 1526: 1419: 1233: 1190: 1173: 1043: 642: 638: 624: 337: 275: 8836: 6810: 6670: 6346: 5726: 5363: 5296: 5223: 5154: 5094: 5036: 4976: 4572: 4344: 4327:

Beall, Cynthia M.; Song, Kijoung; Elston, Robert C.; Goldstein, Melvyn C. (2004-09-28).

4277: 3797: 3560: 3336: 2945: 1468:

Animals other than humans use different molecules to bind to hemoglobin and change its O

1085:

Scientists agree that the event that separated myoglobin from hemoglobin occurred after

8782: 8691: 8686: 8393: 8075: 7801: 7796: 7776: 7634: 7510: 7289: 7256: 6986: 6919: 6894: 6682: 6601: 6576: 6526:

Siebenmann, Christoph; Keiser, Stefanie; Robach, Paul; Lundby, Carsten (29 June 2017).

6411: 6363: 6330: 6311: 6079: 5473: 5261: 5248: 5207: 5179: 5138: 5114: 5055: 5020: 4993: 4960: 4763: 4304: 4261: 4057: 4005: 3972: 3945: 3912: 3888: 3863: 3817: 3545:"A critical study of the direct method of measuring the osmotic pressure of hǣmoglobin" 3520: 3503: 3435: 3355: 3318: 3285: 3256: 3101: 3003: 2724: 2718: 2259: 2071: 2038: 1542: 1355: 968: 937: 925: 891: 757: 628: 470: 6399: 5924: 5905: 5323: 5280: 4984: 4447: 4420: 4371: 4328: 3378: 3047: 3022: 332:

Hemoglobin also transports other gases. It carries off some of the body's respiratory

9020: 8793: 8374: 8269: 7839: 7755: 7721: 7523: 7478: 7460: 7294: 7276: 7243: 7216: 7195: 7189: 7174: 7157: 7126: 7009: 6990: 6949: 6943: 6924: 6875: 6834: 6829: 6794: 6775: 6770: 6753: 6734: 6654: 6606: 6557: 6549: 6508: 6473: 6438: 6403: 6368: 6315: 6303: 6244: 6173: 6071: 5988: 5983: 5966: 5934: 5842: 5819: 5802:

Kikuchi, G.; Yoshida, T.; Noguchi, M. (2005). "Heme oxygenase and heme degradation".

5753: 5730: 5695: 5691: 5660: 5622: 5581: 5559: 5523: 5496: 5465: 5430: 5426: 5395: 5390: 5377: 5347: 5328: 5310: 5265: 5253: 5235: 5184: 5166: 5106: 5060: 4998: 4939: 4916: 4911: 4894: 4877: 4826: 4783: 4755: 4701: 4596: 4591: 4556: 4524: 4478: 4452: 4376: 4358: 4309: 4291: 4049: 4010: 3992: 3950: 3932: 3893: 3844: 3809: 3525: 3427: 3360: 3290: 3255:

Saha, D.; Reddy, K. V. R.; Patgaonkar, M.; Ayyar, K.; Bashir, T.; Shroff, A. (2014).

3237: 3189: 3162: 3126: 3093: 3052: 2995: 2953: 2947: 2926: 2884: 2670: 2334:, also called Vestimentifera), which can reach 2.4 meters length and populates ocean 2287: 2205:

shows good correlation with both the oxy- and deoxyhemoglobin signal compared to the

2066: 2046: 2010: 1907: 1818: 1755: 1669: 1636: 1585: 1515: 1270: 1212:, which binds to hemoglobin in a cooperative manner, hemoglobin ligands also include 1172:

In the tetrameric form of normal adult hemoglobin, the binding of oxygen is, thus, a

1059: 87: 6686: 6574: 6544: 6527: 6083: 4767: 4148: 4061: 3439: 3105: 3007: 8919: 8816: 8811: 8754: 8737: 8279: 8238: 8168: 7656: 7605: 7515: 7430: 7284: 7268: 7235: 7149: 6982: 6978: 6914: 6906: 6865: 6824: 6814: 6765: 6724: 6674: 6596: 6588: 6539: 6504: 6500: 6465: 6415: 6395: 6358: 6350: 6295: 6129: 6063: 5978: 5811: 5722: 5687: 5652: 5457: 5422: 5385: 5367: 5318: 5300: 5243: 5227: 5174: 5158: 5118: 5098: 5050: 5040: 4988: 4980: 4906: 4747: 4691: 4586: 4576: 4518: 4442: 4432: 4366: 4348: 4299: 4281: 4041: 4000: 3984: 3940: 3924: 3883: 3875: 3821: 3801: 3756: 3564: 3515: 3419: 3350: 3340: 3280: 3270: 3229: 3083: 3042: 3034: 2987: 2768: 2692: 2607: 2587: 2497: 2326:

One of the most striking occurrences and uses of hemoglobin in organisms is in the

2281: 2251: 2061: 2017:

also runs high. Because of the slow rate of Hb A combination with glucose, the Hb A

1963: 1903: 1891: 1797: 1761: 1709: 1546: 1488: 1301: 1182: 1090: 1027: 918: 911: 799: 795: 633: 540: 484:

determined the molecular structure of hemoglobin. For this work he shared the 1962

364: 7316: 5477: 4895:"Nature of the FeO2 bonding in myoglobin and hemoglobin: A new molecular paradigm" 4718: 4394: 3423: 100: 8704: 8533: 8388: 7834: 7682: 7651: 7349: 7338: 7120: 6299: 6156: 6103: 6041: 5912: 5885: 4809: 4790: 4725: 4639: 4620: 4504: 4183: 3371: 3183: 3156: 3023:"Is hemoglobin an essential structural component of human erythrocyte membranes?" 2652: 2541: 2513: 2505: 2339: 2327: 1852: 1541:, caused by variations in genetics. Some well-known hemoglobin variants, such as 1293: 1258: 1232:(NO). The carbon dioxide is bound to amino groups of the globin proteins to form 1217: 1105: 887:

will be able to eventually reactivate methemoglobin by reducing the iron center.

733: 650: 556: 536: 384: 259: 7272: 6469: 5517: 5162: 4751: 3988: 3233: 3120: 2606:

in 2005, based on the protein's backbone. The sculpture was made from glass and

752:

and many other species. Even after the loss of the nucleus in mammals, residual

645:

was understood at the molecular level. A mostly separate set of diseases called

9015: 8924: 8853: 8674: 8623: 8435: 8430: 7780: 7770: 7627: 7585: 7450: 7103: 6799: