Structure of human hemoglobin. The protein subunits are in red and blue, and the iron-containing heme groups in green. A heme ( American English) or haem ( British English) is a Prosthetic group that consists of an Iron atom contained in the center of From PDB 1GZX Proteopedia Hemoglobin . The Protein Data Bank ( PDB) is a repository for 3-D structural data of Proteins and Nucleic acids These data typically obtained by X-ray crystallography Proteopedia is a collaborative Wiki 3D encyclopedia of Proteins and other Molecules Proteopedia contains a page for every entry in the Protein Data

Hemoglobin (also spelled haemoglobin and abbreviated Hb or Hgb) is the iron-containing oxygen-transport metalloprotein in the red blood cells of vertebrates. American and British English spelling differences are one aspect of American and British English differences. Iron (ˈаɪɚn is a Chemical element with the symbol Fe (ferrum and Atomic number 26 Oxygen (from the Greek roots ὀξύς (oxys (acid literally "sharp" from the taste of acids and -γενής (-genēs (producer literally begetteris the In Biochemistry, a metalloprotein is a generic term for a Protein that contains a Metal cofactor. Red blood cells are the most common type of Blood cell and the Vertebrate body's principal means of delivering Oxygen to the body tissues via the Blood Vertebrates are members of the Subphylum Vertebrata, Chordates with backbones or spinal columns The grouping sometimes includes ^[1] In mammals, the protein makes up about 97% of the red cell’s dry content, and around 35% of the total content (including water). Mammals ( class Mammalia) are a class of Vertebrate Animals characterized by the presence of Sweat glands, including sweat glands Hemoglobin transports oxygen from the lungs or gills to the rest of the body, such as to the muscles, where it releases the oxygen for cell use. lung is the essential Respiration organ in air-breathing Animals including most Tetrapods a few Fish and a few Snails The most primitive A gill is an anatomical structure found in many aquatic organisms Muscle (from Latin musculus, diminutive of mus "mouse" is contractile tissue of the body and is derived from the It also has a variety of other roles of gas transport and effect-modulation which vary from species to species, and are quite diverse in some invertebrates. An invertebrate is an Animal lacking a Vertebral column. The group includes 98% of all animal Species — all animals except those in the Chordate

Discovery

The oxygen-carrying protein hemoglobin was discovered by Otto Funke in 1851. Otto Funke ( October 27, 1828 - August 17, 1879) was a German Physiologist who was a native of Chemnitz. ^[2] In that year he 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. ^[3] Hemoglobin’s reversible oxygenation was described a few years later by Felix Hoppe-Seyler. Ernst Felix Immanuel Hoppe-Seyler (December 26 1825 &ndash August 10 1895 was a German Physiologist and Chemist. ^[4] In 1959 Max Perutz determined the molecular structure of the molecule. Max Ferdinand Perutz, OM ( May 19 1914, Vienna, Austria – February 6 2002, Cambridge, ^[5] This work resulted in his sharing with John Kendrew the 1962 Nobel Prize in Chemistry. Sir John Cowdery Kendrew ( 24 March 1917 &ndash 23 August 1997) was an English Biochemist and crystallographer The Nobel Prize in Chemistry (Nobelpriset i kemi is awarded annually by the Royal Swedish Academy of Sciences to scientists in the various fields of Chemistry.

The role of Haemoglobin in the blood was discovered by physiologist Claude Bernard. Claude Bernard ( July 12, 1813 – February 10, 1878) was a French Physiologist. The name hemoglobin is the concatenation of heme and globin, reflecting the fact that each subunit of hemoglobin is a globular protein with an embedded heme (or haem) group. A heme ( American English) or haem ( British English) is a Prosthetic group that consists of an Iron atom contained in the center of Globular proteins, or spheroproteins are one of the two main Protein classes comprising "globe" -like proteins that are more or less soluble in In Structural biology, a protein subunit or subunit protein is a single Protein Molecule that assembles (or " coassembles " Globular proteins, or spheroproteins are one of the two main Protein classes comprising "globe" -like proteins that are more or less soluble in A heme ( American English) or haem ( British English) is a Prosthetic group that consists of an Iron atom contained in the center of Each heme group contains one iron atom, that can bind one oxygen molecule through ion-induced dipole forces. An ion is an Atom or Molecule which has lost or gained one or more Valence electrons giving it a positive or negative electrical charge The most common type of hemoglobin in mammals contains four such subunits. Mammals ( class Mammalia) are a class of Vertebrate Animals characterized by the presence of Sweat glands, including sweat glands

Genetics

Mutations in the genes for the hemoglobin protein in a species result in hemoglobin variants,^[6][7] some of which cause a group of hereditary diseases termed the hemoglobinopathies in humans. History See also History of genetics The existence of genes was first suggested by Gregor Mendel (1822-1884 who in the 1860s studied inheritance Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl Hemoglobin ( also spelled haemoglobin and abbreviated Hb or Hgb) is the Iron -containing Oxygen -transport Metalloprotein A genetic disorder is a condition caused by abnormalities in Genes or Chromosomes While some diseases such as Cancer, are due to genetic abnormalities acquired Hemoglobinopathy is a kind of Genetic defect that results in abnormal structure of one of the Globin chains of the Hemoglobin molecule The best known is sickle-cell disease, which was the first human disease whose mechanism was understood at the molecular level. Sickle-cell disease or sickle-cell anaemia (or anemia) is a Blood disorder characterized by Red blood cells that assume an abnormal rigid A (mostly) separate set of diseases called thalassemias involves underproduction of normal and sometimes abnormal hemoglobins, through problems and mutations in globin gene regulation. Thalassemia (from Greek θαλασσα thalassa sea + αίμα haima blood British spelling "thalassaemia" is an inherited Autosomal recessive Gene modulation redirects here For information on therapeutic regulation of gene expression see Therapeutic gene modulation. These diseases also often produce anemia. Anemia ( AmE) or anæmia/anaemia ( BrE) (from the Ancient Greek grc-Latn anaîmia, meaning “without blood” is defined as a qualitative ^[8]

The chemical formulas of hemoglobins vary widely across species, and even (through common mutations) slightly among subgroups of humans.

Synthesis

Hemoglobin (Hb) is synthesized in a complex series of steps. The heme part is synthesized in a series of steps in the mitochondria and the cytosol of immature red blood cells, while the globin protein parts are synthesized by ribosomes in the cytosol. In Cell biology, a mitochondrion (plural mitochondria) is a membrane-enclosed Organelle found in most eukaryotic cells. The cytosol or intracellular fluid (or cytoplasmic matrix) is the liquid found inside cells. Globular proteins, or spheroproteins are one of the two main Protein classes comprising "globe" -like proteins that are more or less soluble in Ribosomes ( from ribo nucleic acid and "Greek soma ( meaning body") are complexes of RNA and Protein that ^[9] Production of Hb continues in the cell throughout its early development from the proerythroblast to the reticulocyte in the bone marrow. A proerythroblast (or rubriblast, or pronormoblast) is the earliest of four stages in development of the Normoblast. Reticulocytes are immature Red blood cells typically composing about 1% of the red cells in the human body Bone marrow is the flexible tissue found in the hollow interior of Bones In adults marrow in large bones produces new Blood cells It constitutes 4% of At this point, the nucleus is lost in mammalian red blood cells, but not in birds and many other species. In Cell biology, the nucleus (pl nuclei; from Latin la ''nucleus'' or la ''nuculeus'' "little nut" or kernel is a membrane-enclosed Birds ( class Aves) are bipedal endothermic ( Warm-blooded) Vertebrate animals that lay eggs. Even after the loss of the nucleus in mammals, residual ribosomal RNA allows further synthesis of Hb until the reticulocyte loses its RNA soon after entering the vasculature (this hemoglobin-synthetic RNA in fact gives the reticulocyte its reticulated appearance and name). Ribosomal RNA ( rRNA) is the central component of the Ribosome, the protein manufacturing machinery of all living cells. This is an article about the rock music band "Circulatory System"

Structure

Heme group

In most humans, the hemoglobin molecule is an assembly of four globular protein subunits. In Chemistry, a molecule is defined as a sufficiently stable electrically neutral group of at least two Atoms in a definite arrangement held together by Globular proteins, or spheroproteins are one of the two main Protein classes comprising "globe" -like proteins that are more or less soluble in Each subunit is composed of a protein chain tightly associated with a non-protein heme group. Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl A heme ( American English) or haem ( British English) is a Prosthetic group that consists of an Iron atom contained in the center of Each protein chain arranges into a set of alpha-helix structural segments connected together in a globin fold arrangement, so called because this arrangement is the same folding motif used in other heme/globin proteins such as myoglobin. A common motif in the Secondary structure of Proteins the alpha helix (α-helix is a right-handed coiled conformation resembling a spring, in which The globin fold is a common three-dimensional fold in Proteins This fold typically consists of eight alpha helices, although some proteins have additional Myoglobin is a single-chain globular Protein of 153 Amino acids containing a Heme ( Iron -containing Porphyrin) Prosthetic ^[10][11] This folding pattern contains a pocket which strongly binds the heme group.

A heme group consists of an iron (Fe) ion (charged atom) held in a heterocyclic ring, known as a porphyrin. A porphyrin is a heterocyclic Macrocycle derived from four Pyrroline subunits interconnected via their α carbon atoms via Methine bridges (=CH- The iron ion, which is the site of oxygen binding, bonds with the four nitrogens in the center of the ring, which all lie in one plane. Nitrogen (ˈnaɪtɹəʤɪn is a Chemical element that has the symbol N and Atomic number 7 and Atomic weight 14 The iron is also bound strongly to the globular protein via the imidazole ring of the F8 histidine residue below the porphyrin ring. Imidazole is a Organic compound with the formula HC3H3N2 This Aromatic Heterocyclic is classified as an Alkaloid Histidine (abbreviated as His or H) is one of the 20 standard Amino acids present in Proteins In the Nutritional sense in A sixth position can reversibly bind oxygen, completing the octahedral group of six ligands. Oxygen binds in an "end-on bent" geometry where one oxygen atom binds 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 octahedron. An octahedron (plural octahedra is a Polyhedron with eight faces

The iron ion may either be in the Fe²⁺ or Fe³⁺ state, but ferrihemoglobin (methemoglobin) (Fe³⁺) cannot bind oxygen. Methemoglobin (British English Methaemoglobin (pronounced "MET-hemoglobin" is a form of the Oxygen -carrying Protein Hemoglobin (British English ^[12] In binding, oxygen temporarily oxidizes Fe to (Fe³⁺), so iron must exist in the +2 oxidation state in order to bind oxygen. The enzyme methemoglobin reductase reactivates hemoglobin found in the inactive (Fe³⁺) state by reducing the iron center. Methemoglobin reductase (also known as cytochrome- b 5 reductase) is a NADH -dependent Enzyme that converts Methemoglobin

In adult humans, the most common hemoglobin type is a tetramer (which contains 4 subunit proteins) called hemoglobin A, consisting of two α and two β subunits non-covalently bound, each made of 141 and 146 amino acid residues, respectively. A tetramer is a Protein with four subunits (tetrameric There are homo-tetramers (all Subunits are identical such as Glutathione S-transferase or This is denoted as α₂β₂. The subunits are structurally similar and about the same size. Each subunit has a molecular weight of about 17,000 daltons, for a total molecular weight of the tetramer of about 68,000 daltons. The unified atomic mass unit ( u) or Dalton ( Da) or sometimes universal mass unit, is an unit of Mass used to express The molecular mass (abbreviated m of a substance, more commonly referred to as molecular weight and abbreviated as MW, is the Mass of one Hemoglobin A is the most intensively studied of the hemoglobin molecules.

The four polypeptide chains are bound to each other by salt bridges, hydrogen bonds, and hydrophobic interactions. Peptides (from the Greek πεπτίδια, "small digestibles" are short Polymers formed from the linking in a defined order of α- Amino In Protein chemistry the term salt bridge or salt bond denotes a relatively weak Ionic bond between positively and negatively charged A hydrogen bond results from a Dipole-dipole force between an Electronegative atom and a Hydrogen atom bonded to Nitrogen, Oxygen In Chemistry, hydrophobicity (from the combining form of water in Attic Greek hydro- and for fear phobos) refers to the physical property of There are two kinds of contacts between the α and β chains: α₁β₁ and α₂β₂.

Oxyhemoglobin is formed during respiration when oxygen binds to the heme component of the protein hemoglobin in red blood cells. This process occurs in the pulmonary capillaries adjacent to the alveoli of the lungs. An alveolus (plural alveoli, from Latin alveolus, "little cavity" is an anatomical structure that has the form of a hollow cavity The oxygen then travels through the blood stream to be dropped off at cells where it is utilized in aerobic glycolysis and in the production of ATP by the process of oxidative phosphorylation. See also Gluconeogenesis, which carries out a process wherein glucose is synthesized rather than catabolized Adenosine-5'-triphosphate ( ATP) is a multifunctional Nucleotide that is most important as a " molecular currency" of intracellular Energy Oxidative phosphorylation is a Metabolic pathway that uses energy released by the oxidation of Nutrients to produce Adenosine triphosphate (ATP It does not, however, help to counteract a decrease in blood pH. Ventilation, or breathing, may reverse this condition by removal of carbon dioxide, thus causing a shift up in pH. In Respiratory physiology, ventilation (or ventilation rate) is the rate at which gas enters or leaves the Lung. Carbon dioxide ( Chemical formula:) is a Chemical compound composed of two Oxygen Atoms covalently bonded to a single ^[13]

Deoxyhemoglobin is the form of hemoglobin without the bound oxygen. The absorption spectra of oxyhemoglobin and deoxyhemoglobin differ. A material's absorption spectrum shows the fraction of incident Electromagnetic radiation absorbed by the material over a range of Frequencies. The oxyhemoglobin has significantly lower absorption of the 660 nm wavelength than deoxyhemoglobin, while at 940 nm its absorption is slightly higher. In Physics wavelength is the distance between repeating units of a propagating Wave of a given Frequency. This difference is used for measurement of the amount of oxygen in patient's blood by an instrument called pulse oximeter. A pulse oximeter is a Medical device that indirectly measures the oxygen saturation of a patient's Blood (as opposed to measuring oxygen saturation directly through

Iron's oxidation state in oxyhemoglobin

Assigning oxygenated hemoglobin's oxidation state is difficult because oxyhemoglobin is diamagnetic (no net unpaired electrons), but the low-energy electron configurations in both oxygen and iron are paramagnetic. Paramagnetism is a form of magnetism which occurs only in the presence of an externally applied magnetic field Triplet oxygen, the lowest energy oxygen species, has two unpaired electrons in antibonding π* molecular orbitals. Triplet oxygen is the Ground state of the Oxygen molecule The Electron configuration of the molecule has two unpaired electrons occupying two degenerate Iron(II) tends to be in a high-spin configuration where unpaired electrons exist in E_g antibonding orbitals. Iron(III) has an odd number of electrons and thus has unpaired electrons. All of these molecules are paramagnetic (have unpaired electrons), not diamagnetic, so an unintuitive distribution of electrons must exist to induce diamagnetism.

The three logical possibilities are:

1. Low-spin Fe²⁺ binds to high-energy singlet oxygen. Both low-spin iron and singlet oxygen are diamagnetic.
2. Low-spin Fe³⁺ binds to . O₂^- (the superoxide ion) and the two unpaired electrons couple antiferromagnetically, giving diamagnetic properties. Superoxide is the Anion O2&minus It is important as the product of the one-electron reduction of Dioxygen, which occurs widely in nature
3. Low-spin Fe⁴⁺ binds to O₂^2-. Both are diamagnetic.

X-ray photoelectron spectroscopy suggests iron has an oxidation state of approximately 3. X-ray Photoelectron Spectroscopy (XPS is a quantitative spectroscopic technique that measures the elemental composition Empirical formula, 2 and infrared stretching frequencies of the O-O bond suggests a bond length fitting with superoxide. Infrared spectroscopy (IR spectroscopy is the subset of Spectroscopy that deals with the Infrared region of the Electromagnetic spectrum. The correct oxidation state of iron is thus the +3 state with oxygen in the -1 state. The diamagnetism in this configuration arises from the unpaired electron on superoxide aligning antiferromagnetically from the unpaired electron on iron. The second choice being correct is not surprising because singlet oxygen and large separations of charge are both unfavorably high-energy states. Iron's shift to a higher oxidation state decreases the atom's size and allows it into the plane of the porphyrin ring, pulling on the coordinated histidine residue and initiating the allosteric changes seen in the globulins. The assignment of oxidation state, however, is only a formalism so all three models may contribute to some small degree.

Early postulates by bioinorganic chemists claimed that possibility (1) (above) was correct and that iron should exist in oxidation state II (indeed iron oxidation state III as methemoglobin, when not accompanied by superoxide . O₂^- to "hold" the oxidation electron, is incapable of binding O₂). The iron chemistry in this model was elegant, but the presence of singlet oxygen was never explained. It was argued that the binding of an oxygen molecule placed high-spin iron(II) in an octahedral field of strong-field ligands; this change in field would increase the crystal field splitting energy, causing iron's electrons to pair into the diamagnetic low-spin configuration. Crystal field theory (CFT is a model that describes the Electronic structure of Transition metal compounds all of which can be considered coordination

Binding of ligands

Another schematic visual model of the same process above, showing all four tetramers and hemes, and protein chains only as diagramatic coils, to facilitate visualization into the molecule. Oxygen is not shown in this model, but binds to the flat heme, as shown in green in the previous model.

Binding and release of ligands induces a conformational (structural) change in hemoglobin. Here, the binding and release of oxygen illustrates the structural differences between oxy- and deoxyhemoglobin, respectively. Only one of the four heme groups is shown.

As illustrated above, when oxygen binds to the iron center, it causes contraction of the iron atom, and causes it to move back into the center of the porphyrin ring plane (see moving diagram). At the same time, the porphyrin ring plane itself is pushed away from the oxygen and toward the imidizole side chain of the histidine residue interacting at the other pole of the iron. The interaction here forces the ring plane sideways toward the outside of the tetramer, and also induces a strain on the protein helix containing the histidine as it moves nearer to the iron. This causes a tug on the peptide strand which tends to open up heme units in the remainder of the molecule, so that there is more room for oxygen molecules to bind at their heme sites.

In the tetrameric form of normal adult hemoglobin, the binding of oxygen is thus a cooperative process. In Biochemistry, a Macromolecule exhibits cooperative binding if its Affinity for its ligand changes with the amount of ligand already bound The binding affinity of hemoglobin for oxygen is increased by the oxygen saturation of the molecule, with the first oxygens bound influencing the shape of the binding sites for the next oxygens, in a way favorable for binding. This positive cooperative binding is achieved through steric conformational changes of the hemoglobin protein complex as discussed above, i. See also Intramolecular forces ' Steric effects arise from the fact that each Atom within a Molecule occupies a certain e. when one subunit protein in hemoglobin becomes oxygenated, this induces a conformational or structural change in the whole complex, causing the other subunits to gain an increased affinity for oxygen. As a consequence, the oxygen binding curve of hemoglobin is sigmoidal, or S-shaped, as opposed to the normal hyperbolic curve associated with noncooperative binding. A sigmoid function is a Mathematical function that produces a sigmoid curve &mdash a curve having an "S" shape In Mathematics, the hyperbolic functions are analogs of the ordinary trigonometric, or circular functions

Hemoglobin's oxygen-binding capacity is decreased in the presence of carbon monoxide because both gases compete for the same binding sites on hemoglobin, carbon monoxide binding preferentially in place of oxygen. Carbon monoxide, with the chemical formula CO is a colorless odorless tasteless yet highly toxic Gas. Carbon dioxide occupies a different binding site on the hemoglobin. Carbon dioxide is more readily dissolved in deoxygenated blood, facilitating 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 Haldane effect. The Haldane effect is a property of Hemoglobin first described by the Scottish Physician John Scott Haldane. 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⁺

The sigmoidal shape of hemoglobin's oxygen-dissociation curve results from cooperative binding of oxygen to hemoglobin. The carbonic anhydrases (or carbonate dehydratases) form a family of Enzymes that catalyze the rapid conversion of Carbon dioxide to Bicarbonate Carbonic acid (ancient name acid of air or aerial acid) has the formula H2CO3 In Inorganic chemistry, bicarbonate ( IUPAC -recommended nomenclature hydrogencarbonate) is an intermediate form in the Deprotonation The proton ( Greek πρῶτον / proton "first" is a Subatomic particle with an Electric charge of one positive

Hence blood with high carbon dioxide levels is also lower in pH (more acidic). pH is the measure of the acidity or alkalinity of a Solution. In Computer science, ACID ( Atomicity Consistency Isolation Durability) is a set of properties that guarantee that Database transactions are 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 along the protein, and carbon dioxide binds at the alpha-amino group forming carbamate. Carbamates, or Urethanes are a group of Organic compounds sharing a common Functional group with the general structure -NH(COO- 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. This control of hemoglobin's affinity for oxygen by the binding and release of carbon dioxide and acid, is known as the Bohr effect. Bohr effect is a property of Hemoglobin first described in 1904 by the Danish physiologist Christian Bohr (father of physicist Niels Bohr) which states

The binding of oxygen is affected by molecules such as carbon monoxide (CO) (for example from tobacco smoking, cars and furnaces). Tobacco Smoking is the inhalation of smoke from burned dried or cured leaves of the Tobacco plant most often in the form of a Cigarette. CO competes with oxygen at the heme binding site. Hemoglobin binding affinity for CO is 200 times greater than its affinity for oxygen, meaning that small amounts of CO dramatically reduce hemoglobin's ability to transport oxygen. When hemoglobin combines with CO, it forms a very bright red compound called carboxyhemoglobin. Carboxyhemoglobin (British English Carboxyhaemoglobin) (COHb is a stable complex of Carbon monoxide and Hemoglobin that forms in red Blood 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), nitrogen dioxide (NO₂), and sulfide (S^2-), including hydrogen sulfide (H₂S). A cyanide is any Chemical compound that contains the cyano group (C≡N which consists of a Carbon Atom triple-bonded to a Sulfur monoxide is a Chemical compound with formula and CAS number 13827-32-2 Nitrogen dioxide is the Chemical compound with the formula N[[Oxygen O]]2 The term sulfide ( sulphide in British English) refers to several types of Chemical compounds containing Sulfur in its lowest Oxidation Hydrogen sulfide (or hydrogen sulphide) is the Chemical compound with the formula H 2 S. 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 be in the ferrous (Fe²⁺) oxidation state to support oxygen and other gases' binding and transport. Oxidation to the ferric (Fe³⁺) state converts hemoglobin into hemiglobin or methemoglobin (pronounced "MET-hemoglobin"), which cannot bind oxygen. Methemoglobin (British English Methaemoglobin (pronounced "MET-hemoglobin" is a form of the Oxygen -carrying Protein Hemoglobin (British English Hemoglobin in normal red blood cells is protected by a reduction system to keep this from happening. Nitrogen dioxide and nitrous oxide are capable of converting a small fraction of hemoglobin to methemoglobin; however, this is not usually of medical importance (nitrogen dioxide is poisonous by other mechanisms, and nitrous oxide is routinely used in surgical anesthesia in most people without undue methemoglobin buildup). Nitrous oxide, commonly known as " laughing gas," is a Chemical compound with the Chemical formula N 2 O.

In people acclimated to high altitudes, the concentration of 2,3-Bisphosphoglycerate (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 oxygen tension. 23-Bisphosphoglycerate (23-BPG also known as 23-diphosphoglycerate or 23-DPG is a three carbon isomer of the glycolytic intermediate 13-bisphosphoglycerate. This phenomenon, where molecule Y affects the binding of molecule X to a transport molecule Z, is called a heterotropic allosteric effect. In Biochemistry, allosteric regulation is the regulation of an Enzyme or other Protein by binding an effector molecule at the protein's allosteric

A variant hemoglobin, called fetal hemoglobin (HbF, α₂γ₂), is found in the developing fetus, and binds oxygen with greater affinity than adult hemoglobin. A fetus (or foetus or fœtus) is a developing Mammal or other Viviparous Vertebrate, after the Embryonic stage and 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. The placenta is an Ephemeral organ present in placental Vertebrates, such as Eutherial Mammals and Sharks during Gestation

Hemoglobin also carries nitric oxide in the globin part of the molecule. Nitric oxide or nitrogen monoxide is a Chemical compound with Chemical formula N[[Oxygen O]] 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 released not in the cytoplasm of erythrocytes but is transported by an anion exchanger called AE1 out of them. Anion Exchanger 1 ( AE1) or Band 3 is a Phylogenetically preserved Transport protein responsible for mediating the electroneutral exchange of ^[14]

Types in humans

Hemoglobin variants are a part of the normal embryonic and fetal development, but may also be pathologic mutant forms of hemoglobin in a population, caused by variations in genetics. Human embryogenesis is the process of Cell division and Cellular differentiation of the human Embryo during early Prenatal development. A fetus (or foetus or fœtus) is a developing Mammal or other Viviparous Vertebrate, after the Embryonic stage and In Biology a population is the collection of inter-breeding organisms of a particular Species; in Sociology Some well-known hemoglobin such variants such as sickle-cell anemia are responsible for diseases, and are considered hemoglobinopathies. Sickle-cell disease or sickle-cell anaemia (or anemia) is a Blood disorder characterized by Red blood cells that assume an abnormal rigid Other variants cause no detectable pathology, and are thus considered non-pathological variants. Pathology (from Greek grc πάθος pathos, "fate harm" and grc -λογία -logia) is the study and ^[15][16]

In the embryo:

• Gower 1 (ζ₂ε₂)
• Gower 2 (α₂ε₂) (PDB 1A9W)
• Hemoglobin Portland (ζ₂γ₂)

In the fetus:

• Hemoglobin F (α₂γ₂) (PDB 1FDH)

In adults:

• Hemoglobin A (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. The Entrez Global Query Cross-Database Search System is a powerful Federated search engine or Web portal that allows users to search many discrete Health sciences The Human Genome Organisation (HUGO is an organization involved in the Human Genome Project, a project about mapping the human genome The Mendelian Inheritance in Man project is a Database that catalogues all the known Diseases with a genetic component, and—when possible—links them The National Center for Biotechnology Information ( NCBI) is part of the United States National Library of Medicine (NLM a branch of the National Institutes Swiss-Prot is a manually curated Biological database of Protein sequences In the fields of Genetics and Evolutionary computation, a locus (plural loci) is a fixed position on a Chromosome such as the position of a Chromosome 16 is one of the 23 pairs of Chromosomes in Humans People normally have two copies of this chromosome The Entrez Global Query Cross-Database Search System is a powerful Federated search engine or Web portal that allows users to search many discrete Health sciences The Human Genome Organisation (HUGO is an organization involved in the Human Genome Project, a project about mapping the human genome The Mendelian Inheritance in Man project is a Database that catalogues all the known Diseases with a genetic component, and—when possible—links them The National Center for Biotechnology Information ( NCBI) is part of the United States National Library of Medicine (NLM a branch of the National Institutes Swiss-Prot is a manually curated Biological database of Protein sequences In the fields of Genetics and Evolutionary computation, a locus (plural loci) is a fixed position on a Chromosome such as the position of a Chromosome 16 is one of the 23 pairs of Chromosomes in Humans People normally have two copies of this chromosome The Entrez Global Query Cross-Database Search System is a powerful Federated search engine or Web portal that allows users to search many discrete Health sciences The Human Genome Organisation (HUGO is an organization involved in the Human Genome Project, a project about mapping the human genome The Mendelian Inheritance in Man project is a Database that catalogues all the known Diseases with a genetic component, and—when possible—links them The National Center for Biotechnology Information ( NCBI) is part of the United States National Library of Medicine (NLM a branch of the National Institutes Swiss-Prot is a manually curated Biological database of Protein sequences In the fields of Genetics and Evolutionary computation, a locus (plural loci) is a fixed position on a Chromosome such as the position of a Chromosome 11 is one of the 23 pairs of Chromosomes in Humans People normally have two copies of this chromosome An embryo (from Greek:, plural, lit "that which grows" from en- "in" + bryein "to swell be full" is a multicellular The Protein Data Bank ( PDB) is a repository for 3-D structural data of Proteins and Nucleic acids These data typically obtained by X-ray crystallography A fetus (or foetus or fœtus) is a developing Mammal or other Viviparous Vertebrate, after the Embryonic stage and The Protein Data Bank ( PDB) is a repository for 3-D structural data of Proteins and Nucleic acids These data typically obtained by X-ray crystallography The Protein Data Bank ( PDB) is a repository for 3-D structural data of Proteins and Nucleic acids These data typically obtained by X-ray crystallography 5-3. 5%
• Hemoglobin F (α₂γ₂) - 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.

Variant forms which cause disease:

• Hemoglobin S (α₂β^S₂) - A variant form of hemoglobin found in people with sickle cell disease. Sickle-cell disease or sickle-cell anaemia (or anemia) is a Blood disorder characterized by Red blood cells that assume an abnormal rigid There is a variation in the β-chain gene, causing a change in the properties of hemoblobin which results in sickling of red blood cells.
• Hemoglobin C (α₂β^C₂) - Another variant due to a variation in the β-chain gene. Hemoglobin C (abbreviated as Hb C or HbC) is an abnormal Hemoglobin with substitution of a Lysine residue for Glutamic acid residue This variant causes a mild chronic hemolytic anemia. Hemolytic anemia is Anemia due to Hemolysis, the abnormal breakdown of Red blood cells (RBCs either in the Blood vessels (intravascular hemolysis

Degradation in vertebrate animals

When red cells reach the end of their life due to aging or defects, they are broken down, the hemoglobin molecule is broken up and the iron gets recycled. Red blood cells are the most common type of Blood cell and the Vertebrate body's principal means of delivering Oxygen to the body tissues via the Blood When the porphyrin ring is broken up, the fragments are normally secreted in the bile by the liver. Bile or gall is a bitter yellow or green Alkaline fluid secreted by Hepatocytes from the Liver of most Vertebrates In many species The liver is a vital organ in the human body and is present in Vertebrates and some other animals This process also produces one molecule of carbon monoxide for every molecule of heme degraded [1]; this is one of the few natural sources of carbon monoxide production in the human body, and is responsible for the normal blood levels of carbon monoxide even in people breathing pure air. The other major final product of heme degradation is bilirubin. Bilirubin (formerly referred to as hematoidin) is the yellow breakdown product of normal Heme Catabolism. Increased levels of this chemical are detected in the blood if red 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. The kidneys are complicated organs that have numerous biological roles

Role in disease

In sickle cell hemoglobin (HbS) glutamic acid in position 6 (in beta chain) is mutated to valine. This change allows the deoxygenated form of the hemoglobin to stick to each other.

Decrease of hemoglobin, with or without an absolute decrease of red blood cells, leads to symptoms of anemia. Anemia ( AmE) or anæmia/anaemia ( BrE) (from the Ancient Greek grc-Latn anaîmia, meaning “without blood” is defined as a qualitative Anemia has many different causes, although iron deficiency and its resultant iron deficiency anemia are the most common causes in the Western world. For a more specific and detailed discussion of Anemia caused by iron deficiency see the Wikipedia article Iron deficiency anemia. For a discussion of iron deficiency more broadly see the Wikipedia article iron deficiency. As absence of iron decreases heme synthesis, red blood cells in iron deficiency anemia are hypochromic (lacking the red hemoglobin pigment) and microcytic (smaller than normal). Other anemias are rarer. In hemolysis (accelerated breakdown of red blood cells), associated jaundice is caused by the hemoglobin metabolite bilirubin, and the circulating hemoglobin can cause renal failure. Hemolysis (or haemolysis)—from the Greek Hemo-, Greek meaning blood - Lysis, meaning to break open—is the breaking Jaundice, also known as icterus (attributive adjective "icteric" is yellowish discoloration of the Skin, sclerae (whites of the eyes Renal failure or kidney

Some mutations in the globin chain are associated with the hemoglobinopathies, such as sickle-cell disease and thalassemia. Hemoglobinopathy is a kind of Genetic defect that results in abnormal structure of one of the Globin chains of the Hemoglobin molecule Sickle-cell disease or sickle-cell anaemia (or anemia) is a Blood disorder characterized by Red blood cells that assume an abnormal rigid Thalassemia (from Greek θαλασσα thalassa sea + αίμα haima blood British spelling "thalassaemia" is an inherited Autosomal recessive Other mutations, as discussed at the beginning of the article, are benign and are referred to merely as hemoglobin variants. Hemoglobin ( also spelled haemoglobin and abbreviated Hb or Hgb) is the Iron -containing Oxygen -transport Metalloprotein

There is a group of genetic disorders, known as the porphyrias that are characterized by errors in metabolic pathways of heme synthesis. Porphyrias are a group of inherited or acquired disorders of certain Enzymes in the Heme biosynthetic pathway (also called Porphyrin pathway King George III of the United Kingdom was probably the most famous porphyria sufferer. George III (George William Frederick 4 June 1738 George III's long reign was marked by a series of military conflicts involving his kingdom much of the rest of Europe and places

To a small extent, hemoglobin A slowly combines with glucose at the terminal valine (an alpha aminoacid) of each β chain. Glucose (Glc a Monosaccharide (or simple Sugar) also known as grape sugar, is an important Carbohydrate in Biology. The resulting molecule is often referred to as Hb A_1c. Glycosylated (or glycated hemoglobin ( hemoglobin A1c Hb1c, or HbA1c) is a form of Hemoglobin used primarily to identify the average As the concentration of glucose in the blood increases, the percentage of Hb A that turns into Hb A_1c increases. In diabetics whose glucose usually runs high, the percent Hb A_1c also runs high. Diabetes mellitus (ˌdaɪəˈbiːtiːz or /ˌdaɪəˈbiːtəs/ /məˈlaɪtəs/ or /ˈmɛlətəs/ often referred to simply as diabetes ( Ancient Greek: grc Because of the slow rate of Hb A combination with glucose, the Hb A_1c percentage is representative of glucose level in the blood averaged over a longer time (the half-life of red blood cells, which is typically 50-55 days).

Diagnostic uses

Hemoglobin concentration measurement is among the most commonly performed blood tests, usually as part of a complete blood count. A blood test is a laboratory analysis performed on a Blood sample that is usually extracted from a Vein in the arm using a needle, or via A complete blood count ( CBC) also known as full blood count ( FBC) or full blood exam ( FBE) or blood panel, is For example it is typically tested before blood donation. Results are reported in g/L, g/dL or mol/L. For other uses of the words gram or gramme see Gram (disambiguation. The litre or liter (see spelling differences) is a unit of Volume. The litre or liter (see spelling differences) is a unit of Volume. The mole (symbol mol) is a unit of Amount of substance: it is an SI base unit, and almost the only unit to be used to measure this 1 g/dL equals about 0. 6206 mmol/L, and 1 g/L equals about 0. 06206 mmol/L. Normal levels are:

• Women: 12. 1 to 15. 1 g/dl
• Men: 13. 5 to 16. 5 g/dl
• Children: 11 to 16 g/dl
• Pregnant women: 11 to 12 g/dl ^[17]

If the concentration is below normal, this is called anemia. Anemia ( AmE) or anæmia/anaemia ( BrE) (from the Ancient Greek grc-Latn anaîmia, meaning “without blood” is defined as a qualitative Anemias are classified by the size of red blood cells, the cells which contain hemoglobin in vertebrates. The cell is the structural and functional unit of all known living Organisms It is the smallest unit of an organism that is classified as living and is often called 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 level. The hematocrit ( Ht or HCT) or packed cell volume ( PCV) or erythrocyte volume fraction (EVF is the proportion of Blood For example, if the hemoglobin is measured at 17, that compares with a hematocrit of 51. ^[18]

Long-term control of blood sugar concentration can be measured by the concentration of Hb A_1c. Blood sugar, used in a physiological context is a misnomer and misleading Measuring it directly would require many samples because blood sugar levels vary widely through the day. Hb A_1c is the product of the reversible reaction of hemoglobin A with glucose. A reversible reaction is a Chemical reaction that results in an equilibrium mixture of Reactants and products. Glucose (Glc a Monosaccharide (or simple Sugar) also known as grape sugar, is an important Carbohydrate in Biology. A higher glucose concentration results in more Hb A_1c. In Chemistry, concentration is the measure of how much of a given substance there is mixed with another substance Because the reaction is slow, the Hb A_1c proportion represents glucose level in blood averaged over the half-life of red blood cells, is typically 50-55 days. An Hb A_1c 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. Diabetes mellitus (ˌdaɪəˈbiːtiːz or /ˌdaɪəˈbiːtəs/ /məˈlaɪtəs/ or /ˈmɛlətəs/ often referred to simply as diabetes ( Ancient Greek: grc ^[19]

The functional magnetic resonance imaging (fMRI) machine may use the signal from oxyhemoglobin as it partially aligns these molecules with the magnetic field. Functional MRI or functional Magnetic Resonance Imaging (fMRI is a type of specialized MRI scan The machine sends a series of magnetic pulses at the participant's head or other body structure, slowly knocking the molecules out of alignment, and a radio wave is emitted when they are back in alignment. The machine can then pick up these signals and use them to make scans, which are cross-sectional maps showing blood flow.

Analogues in non-vertebrate organisms

A variety of oxygen transport and binding proteins exist in organisms throughout the animal and plant kingdoms. Organisms including bacteria, protozoans and fungi all have hemoglobin-like proteins whose known and predicted roles include the reversible binding of gaseous ligands. The Bacteria ( singular: bacterium) are a large group of unicellular Microorganisms Typically a few Micrometres in length bacteria have Protozoa (in Greek πρῶτον proton "first" and ζῷα zoia "animals" are unicellular Eukaryotes (singular A fungus (ˈfʌŋgəs is a eukaryotic Organism that is a member of the kingdom Fungi (ˈfʌndʒaɪ In Chemistry, a ligand is either an Atom, Ion, or Molecule (see also Functional group) that bonds to a central metal generally Since many of these proteins contain globins and the heme moiety (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 Organic chemistry, functional groups are specific groups of Atoms within Molecules that are responsible for the characteristic Chemical reactions In particular, the distinction of “myoglobin” and hemoglobin in lower animals is often impossible, because some of these organisms do not contain muscles. Muscle (from Latin musculus, diminutive of mus "mouse" is contractile tissue of the body and is derived from the Or, they may have a recognizable separate circulatory system but not one which deals with oxygen transport (for example, many insects and other arthropods). This is an article about the rock music band "Circulatory System" Insects ( Class Insecta) are a major group of Arthropods and the most diverse group of Animals on the Earth with over a million described Arthropods are Animals belonging to the Phylum Arthropoda (from Greek ἄρθρον arthron, " Joint " In all these groups, heme/globin containing molecules (even monomeric globin ones) which deal with gas-binding are referred to as hemoglobins. In addition to dealing with transport and sensing of oxygen, they may also deal with NO, CO₂, sulfide compounds, and even O₂ scavenging in environments which must be anaerobic. They may even deal with detoxification of chlorinated materials in a way analogous to heme-containing P450 enzymes and peroxidases.

The giant tube worm Riftia pachyptila showing red hemoglobin-containing plumes

The structure of hemoglobins varies across species. Giant tube worms, Riftia pachyptila, are marine Invertebrates in the phylum Annelida ref> (formerly grouped in phylum Pogonophora Hemoglobin occurs in all kingdoms of organisms, but not in all organisms. Primitive species such as bacteria, protozoa, algae, and plants often have single-globin hemoglobins. Algae ( sing. alga are a large and diverse group of simple typically Autotrophic organisms ranging from Unicellular to Multicellular forms Plants are living Organisms belonging to the kingdom Plantae. Many nematode worms, molluscs and crustaceans contain very large multisubunit molecules, much larger than those in vertebrates. The nematodes or roundworms ( Phylum Nematoda from Greek (nema "thread" + -ode "like" are one of the most common Molluscs are animals belonging to the phylum Mollusca. There are around 250000 extant Species within the phylum with an estimated 70000 Structure of crustaceans As Arthropods crustaceans have a stiff Exoskeleton, which must be shed to allow the animal to grow ( Ecdysis or molting Particularly, chimeric hemoglobins found in fungi and giant annelids may contain both globin and other types of proteins. A fungus (ˈfʌŋgəs is a eukaryotic Organism that is a member of the kingdom Fungi (ˈfʌndʒaɪ The annelids, collectively called Annelida (from Latin anellus "little ring" are a large phylum of Animals comprising ^[20]

One of the most striking occurrences and uses of hemoglobin in organisms is in the giant tube worm (Riftia pachyptila, also called Vestimentifera) which can reach 2. Giant tube worms, Riftia pachyptila, are marine Invertebrates in the phylum Annelida ref> (formerly grouped in phylum Pogonophora 4 meters length and populates ocean volcanic vents. Plate tectonics and hotspots Divergent plate boundaries At the Instead of a digestive tract, these worms contain a population of bacteria constituting half the organism’s weight. The bacteria react with H₂S from the vent and O₂ from the water to produce energy to make food from H₂O and CO₂. The worms end with a deep red fan-like structure ("plume") which extends into the water and absorbs H₂S and O₂ for the bacteria, and CO₂ for use as synthetic raw material similar to photosynthetic plants. The structures are bright red due to containing several extraordinarily complex hemoglobins which have up to 144 globin chains, each presumably including associated heme structures. These hemoglobins are remarkable for being able to carry 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. ^[21][22]

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. Myoglobin is a single-chain globular Protein of 153 Amino acids containing a Heme ( Iron -containing Porphyrin) Prosthetic It is very similar to hemoglobin in structure and sequence, but is not a tetramer; instead, it is a monomer that lacks cooperative binding. In Biochemistry, a Macromolecule exhibits cooperative binding if its Affinity for its ligand changes with the amount of ligand already bound 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. Hemocyanins (also spelled haemocyanins) are respiratory Proteins in the form of Metalloproteins containing two Copper atoms that reversibly Arthropods are Animals belonging to the Phylum Arthropoda (from Greek ἄρθρον arthron, " Joint " Molluscs are animals belonging to the phylum Mollusca. There are around 250000 extant Species within the phylum with an estimated 70000 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. Hemerythrin (also spelled haemerythrin; from Greek words αίμα = blood and ερυθρός = red is an Oligomeric Protein responsible for Oxygen The annelids, collectively called Annelida (from Latin anellus "little ring" are a large phylum of Animals comprising 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. Chlorocruorin is an oxygen carrying blood protein of many Annelids it is noted for appearing green when deoxygenated (as opposed to dark red like Hemoglobin) though Appears green when deoxygenated and red when oxygenated.

Vanabins: Also known as vanadium chromagens, they are found in the blood of sea squirts and are hypothesised to use the rare metal vanadium as its oxygen binding prosthetic group. Vanabins (also known as vanadium-associated proteins or vanadium chromagen) are a specific group of Vanadium -binding Metalloproteins Found Vanadium (vəˈneɪdiəm is a Chemical element that has the symbol V and Atomic number 23 Tunicate, also known as urochordata, tunicata (and by the common names of urochordates, sea squirts, and sea pork) is the

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. Erythrocruorin is a large Oxygen -carrying Protein, whose Molecular mass is greater than 3 Earthworm is the usual name for the largest members of Oligochaeta (which is either a class or subclass depending on the author in the phylum Annelida In classical 5 million daltons.

Pinnaglobin: Only seen in the mollusc Pinna squamosa. Brown manganese-based porphyrin protein.

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 oxygen carrier leghemoglobin (also legoglobin) is a Hemoprotein found in the nitrogen-fixing root nodules of leguminous plants The specific enzyme protected is nitrogenase, which is unable to reduce nitrogen gas in the presence of free oxygen. Nitrogenase ( is the Enzyme used by some organisms to fix atmospheric Nitrogen gas (N2

In history and art

The planet Mars

Historically, the color of blood was associated with rust, as ancient Romans associated the planet Mars with the god of war since Mars is orange-red. Ancient Rome was a Civilization that grew out of a small agricultural community founded on the Italian Peninsula as early as the 10th century BC The color of Mars is due to iron-oxygen in the Martian soil, but the red in blood is not due to the iron in hemoglobin and its oxides, which is a common misconception. The red is due to the porphyrin moiety of hemoglobin to which the iron is bound, not the iron itself,^[23] although the ligation and redox state of the iron can influence the pi to pi* electronic transitions of the porphyrin and hence its optical characteristics. A porphyrin is a heterocyclic Macrocycle derived from four Pyrroline subunits interconnected via their α carbon atoms via Methine bridges (=CH- In Organic chemistry, functional groups are specific groups of Atoms within Molecules that are responsible for the characteristic Chemical reactions

Heart of Steel (Hemoglobin) by Julian Voss-Andreae. The images show the 5' (1. 60 m) tall sculpture right after installation, after 10 days, and after several months of exposure to the elements.

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. Weathering steel, best-known under the trademark COR-TEN steel is a group of Steel alloys which were developed to obviate the need for painting and form a stable The intentional rusting of the initially shiny work of art mirrors hemoglobin's fundamental chemical reaction of iron binding to oxygen. ^[24]

See also

• Chlorophyll
• Globin fold
• Hemocyanin
• Hemoprotein
• Sickle-cell disease

Hemoglobin variants:

• Hb A_1C
• Hemoglobin A2
• Hemoglobin C
• Hemoglobin F

Hemoglobin protein subunits (genes):

• Alpha globin 1
• Beta globin
• Delta globin

Citations

References

External links

• Interactive models of hemoglobin (Requires MDL Chime)
• Interactive hemoglobin saturation curves
• National Anemia Action Council - anemia. org
• Pulse Oximetry Glossary
• New hemoglobin type causes mock diagnosis with pulse oxymeters