Hemoglobin

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. Eventually an oily, varnish-like ink made of soot, turpentine, and walnut oil was created specifically for the printing press. Brown manganese-based porphyrin protein. Neither of these handwriting inks could adhere to printing surfaces without creating blurs. Pinnaglobin: Only seen in the mollusk Pinna squamosa. Two types of ink were prevelent at the time; The Greek and Roman writing ink (soot, glue, and water) and the 12th century variety composed of ferrous sulfate, nutgall, gum, and water. Giant free-floating blood protein, contains many dozens even hundreds of Iron heme containing protein subunits bound together into a single protein complex with a molecular masses greater than 3.5 million daltons.
In the 14th century, a new type of ink had to be developed in Europe for the printing press.

Erythrocruorin: found in many annelids, including earthworms. Once dried, the mixture was mixed with wine and iron salt over a fire to make the final ink. Vanabins: also known as Vanadium Chromagen are found in the blood of Sea squirt and are hypothesised to use the rare metal Vanadium as its oxygen binding prosthetic group, but this hypothesis is unconfirmed. The ink was poured into special bags and hung in the sun. Appears pink/violet when oxygenated, clear when not. Wine was added during boiling. Hemerythrin: Some marine invertebrates and a few species of annelid use this iron containing non-heme protein to carry oxygen in their blood. The water was boiled until it thickened and turned black.

Uses copper prosthetic group instead of iron heme groups and is blue in color when oxygenated. Then the bark was pounded from the branches and soaked in water for eight days. Found in the blood of many arthropods and molluscs. One 12th-century ink recipe called for hawthorn branches to be cut in the spring and left to dry. Hemocyanin: Second most common oxygen transporting protein found in nature. Scribes in medieval Europe (about AD 800 to 1500) wrote on sheepskin parchment. Is very similar to hemoglobin in structure and sequence, but is not arranged in tetramers, it is a monomer and lacks cooperative binding and is used to store oxygen rather than transport it. Over time it fades to a dull brown.

Myoglobin: Found in the muscle tissue of many vertebrates including humans (gives muscle tissue a distinct red or dark gray color). When first put to paper, this ink is bluish-black. Other organisms including bacteria, protozoans and fungi all have hemoglobin-like proteins whose known and predicted roles include the reversible binding of gaseous ligands. Iron "salts," such as ferrous sulfate (made by treating iron with sulfuric acid), was mixed with tannin from gallnuts (they grow on trees) and a thickener. Hemoglobin is by no means unique; there are a variety of oxygen transport and binding proteins throughout the animal (and plant) kingdom. The recipe was used for centuries. 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. About 1,600 years ago, a popular ink recipe was created.

In these individuals an alternative test called "fructosamine level" can be used. Huntington describes these other historical inks:. In individuals with abnormal RBCs, whether due to abnormal hemoglobin molecules (such as Hemoglobin S in Sickle Cell Anemia) or RBC membrane defects - or other problems, the RBC half-life is frequently shortened. In an article for the Christian Science Monitor, Sharon J.
This Hb A_1c level is only useful in individuals who have red blood cells (RBCs) with normal survivals (i.e., normal half-life). Other early cultures also developed inks (of many colors) from available berries, plants and minerals. This test is especially useful for diabetics. This early ink was a mixture of soot from pine smoke, lamp oil, and gelatin from animal skins and musk.

Hb A_1c values which are more than 7.0% are elevated. Approximately 5000 years ago, the Chinese developed ink for blackening the raised surfaces of pictures and texts carved in stone. People whose Hb A_1c runs 6.0% or less show good longer-term glucose control. Denpending the sources and kind of the pigments so they have some special properties of ink like that : Brighness , Satulation, Hue. For this reason a blood sample may be analyzed for Hb A_1c level, which is more representative of glucose control averaged over a longer time period (determined by the half-life of the individual's red blood cells, which is typically 50-55 days). The size of the pigment is very important for the ability of diffuse in the solution inks.
Glucose levels in blood can vary widely each hour, so one or only a few samples from a patient analyzed for glucose may not be representative of glucose control in the long run. Pigments are the main components of the Inks.

For conversion, 1 g/dl is 0.62 mmol/L. Pigments contain the different colors. Results are reported in g/L, g/dl or mmol/L. A disadvantage of dye-based inks is that they can be more susceptible to fading, especially when exposed to ultraviolet radiation as in sunlight. Hemoglobin levels are amongst the most commonly performed blood tests, usually as part of a full blood count or complete blood count. Thus, if an optical brightener or colour enhancer absorbs light energy and emits it through or with the dye, the appearance changes, as the spectrum of light re-emitted to the observer changes. 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). The colour emerges as a function of the light energy that falls on the dye.

In diabetics whose glucose usually runs high, the percent Hb A_1c also runs high. Because dyes get their colour from the interaction of electrons in their molecules, the way in which the electrons can move is determined by the charge and extent of electron delocalisation in the other ink ingredients. As the concentration of glucose in the blood increases, the percentage of Hb A that turns into Hb A_1c increases. This means that they can benefit more than pigmented ink from optical brighteners and colour-enhancing agents designed to increase the intensity and appearance of dyes. The resulting molecule is often referred to as Hb A_1c. An additional advantage of dye-based ink systems is that the dye molecules interact chemically with other ink ingredients. To a small extent, hemoglobin A slowly combines with glucose at a certain location in the molecule. Such a compound in common use in ink-jet printing inks is polyvinyl pyrrolidone.

King George III of the United Kingdom was probably the most famous porphyria sufferer. Cellulose, the material that paper is made of, is also naturally charged, and so a compound that complexes with both the dye and the paper surface aids retention at the surface. There is a group of genetic disorders, known as the porphyrias that are characterized by errors in metabolic pathways of heme synthesis. If the dye has the opposite charge, then it is attracted to and retained by this coating, while the solvent soaks into the paper. Mutations in the globin chain are associated with the haemoglobinopathies, such as sickle-cell disease and thalassemia. The latter is particularly suited to inks that are used in non-industrial settings (and thus must conform to tighter toxicity and emission controls), such as inkjet printer inks, include coating the paper with a charged coating. 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. Other methods to resolve this include harder paper sizing and more specialized paper coatings.

Other anemias are rarer. To circumvent this problem, dye-based inks are made with solvents that dry rapidly or are used with quick-drying methods of printing, such as blowing hot air on the fresh print. 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). However, because dyes are dissolved in the liquid phase, they have a tendency to soak into paper, thus making the ink less efficient and also potentially allowing for the ink to bleed at the edges, producing poor quality printing. Anemia has many different causes, although iron deficiency and its resultant iron deficiency anemia are the most common causes in the Western world. Dyes, however, are generally much stronger and can produce more color of a given density per unit of mass. Decreased levels of hemoglobin, with or without an absolute decrease of red blood cells, leads to symptoms of anemia. This is desirable because more ink on the surface of the paper means less ink needs to be used to create the same intensity of color.

Improperly degraded haemoglobin protein or haemoglobin that has been released from the blood cells can clog small blood vessels especially the delicate blood filtering vessels of the kidneys, causing kidney damage. Pigmented inks are advantageous when printing on paper because the pigment stays on the surface of the paper. Increased levels of this chemical are detected in the blood if red cells are being destroyed more rapidly than usual. These materials are typically referred to as resins (in solvent-based inks) or binding agents (in water-based inks). The major final product of haem degradation is bilirubin. Pigmented inks contain other agents that ensure adhesion of the pigment to the surface and prevent it from being removed by mechanical abrasion. When the porphyrin ring is broken up, the fragments are normally secreted in the bile by the liver. Walnut ink and iron-gall nut ink were made and used by many of the early masters to obtain the golden brown ink used for drawing.

When red cells reach the end of their life due to aging or defects, they are broken down, and the haemoglobin molecule broken up and the iron recycled. India ink is black and originated in Asia. As a result, fetal blood in the placenta is able to take oxygen from maternal blood. Early varieties of ink include Indian ink, various natural dyes made from metals, the husk or outer covering of nuts or seeds, and sea creatures like the squid (known as sepia ). 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. . A variant hemoglobin, called fetal hemoglobin (Hb F, α₂γ₂), is found in the developing fetus, and binds oxygen with greater affinity than adult hemoglobin. However ink can be of a paste form, this kind of ink is used most extensively in letterpress and lithographic printing.

This phenomenon, where molecule Y affects the binding of molecule X to a transport molecule Z, is called a heterotropic allosteric effect. Common perceptions consider ink for use in drawing or writing with a pen or brush. In people acclimated to high altitudes, the concentration of 2,3-diphosphoglycerate (2,3-DPG) in the blood is increased, which allows these individuals to deliver a larger amount of oxygen to tissues under conditions of lower oxygen tension. An ink is a liquid containing various pigments and/or dyes used for colouring a surface to render an image or text. Nitrogen dioxide and nitrous oxide are capable of converting hemoglobin to methemoglobin. "A History of Technology and Invention" by Maurice Audin, page 630. Oxidation to Fe⁺³ state converts hemoglobin into hemiglobin or methemoglobin which cannot bind oxygen. Huntington, Christian Science Monitor, September 21, 2004, retrieved January 17, 2006.

The iron atom in the heme group must be in the Fe⁺² oxidation state to support oxygen transport. "Think Ink!" by Sharon J. Hemoglobin also has competitive binding affinity for sulfur monoxide (SO), nitrogen dioxide (NO₂) and hydrogen sulfide (H₂S). In heavy smokers, up to 20% of the oxygen-active sites can be blocked by CO. 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.

When hemoglobin combines with CO, it forms a very bright-red compound called carboxyhemoglobin. Hemoglobin binding affinity for CO is 200 times greater than its affinity for oxygen, meaning that small amounts of CO dramatically reduces hemoglobin’s ability to transport oxygen. CO competes with oxygen at the heme binding site. The binding of oxygen is affected by molecules such as carbon monoxide (CO) (for example from tobacco smoking, cars and furnaces).

This control of hemoglobin's affinity for oxygen by the binding and release of carbon dioxide is known as the Bohr effect. Conversely, when the carbon dioxide levels in the blood decrease (i.e., around the lungs), carbon dioxide is released, increasing the oxygen affinity of the protein. Protons bind at various places along the protein and carbon dioxide binds at the alpha-amino group forming carbamate. Hemoglobin can bind protons and carbon dioxide which causes a conformational change in the protein and facilitates the release of oxygen.

So blood with high carbon dioxide levels is also lower in pH (more acidic). Carbon dioxide reacts with water to give bicarbonate, carbonic acid freed protons via the reaction, which is catalyzed by carbonic anhydrase:. Carbon dioxide occupies a different binding site on the hemoglobin. Hemoglobin's affinity for oxygen is decreased in the presence of carbon monoxide because both gases compete for the same binding sites on hemoglobin, carbon monoxide binding preferentially to oxygen.

This positive cooperative binding is achieved through steric conformational changes of the hemoglobin protein complex: When one subunit protein in hemoglobin becomes oxygenated, it induces a confirmation or structural arrangement change in the whole complex causing the other 3 subunits to gain an increased affinity for oxygen. As a consequence, the oxygen binding curve of hemoglobin is sigmoidal, or 'S'-shape, as opposed to the normal hyperbolic (noncooperative) curve. The binding affinity of hemoglobin for oxygen is increased by the oxygen saturation of the molecule. In the tetrameric form of normal adult hemoglobin, the binding of oxygen is a cooperative process.

In adults:. In the fetus:. In the embryo:. There are two kinds of contacts between the α and β chains: α₁β₁ and α₁β₂.

The four polypeptide chains are bound to each other by salt bridges, hydrogen bonds and hydrophobic interaction. Haemoglobin A is the most intensively studied of the haemoglobin molecules. Each subunit has a molecular weight of about 16,000 daltons, for a total molecular weight of the tetramer of about 64,000 daltons. The subunits are structurally similar and about the same size.

This is denoted as α₂β₂. In adult humans, the most common haemoglobin type is a tetramer (which contains 4 subunit proteins) called haemoglobin A, consisting of two α and two β subunits non-covalently bound. The iron atom can either be in the Fe²⁺ or Fe³⁺ state, but ferrihaemoglobin (Methaemoglobin) (Fe³⁺) cannot bind oxygen. Two additional bonds perpendicular to the plane on each side can be formed with the iron to form the fifth and sixth positions, one connected strongly to the protein, the other available for binding of oxygen.

The iron atom is bonded equally to all four nitrogens in the center of the ring, which lie in one plane. This iron atom is the site of oxygen binding. A heme group consists of an iron atom held in a heterocyclic ring, known as a porphyrin. This folding pattern contains a pocket which is suitable to strongly bind the heme group.

Each individual protein chain arranges in a set of alpha-helix structural segments connected together in a "myoglobin fold" arrangment, so called because this arrangment is the same folding motif used in the heme/globin proteins. Each subunit is composed of a protein chain tightly associated with a non-protein heme group. The Haemoglobin molecule is an assembly of four globular protein subunits. .

Mutations in the gene for the haemoglobin protein result in a group of hereditary diseases termed the hemoglobinopathies, the most common members of which are sickle-cell disease and thalassemia. The most common types of hemoglobin contains four such subunits. 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; each heme group contains an iron atom, and this is responsible for the binding of oxygen. Hemoglobin transports oxygen from the lungs to the rest of the body, such as to the muscles, where it releases the oxygen load.

Hemoglobin or haemoglobin (frequently abbreviated as Hb) is the iron-containing oxygen-transport metalloprotein in the red cells of the blood in mammals and other animals. Haemoglobin F (α₂γ₂) - In adults Haemoglobin F is restricted to a limited population of red cells called F cells. Haemaglobin A₂ (α₂δ₂) - δ chain synthesis begins late in the third trimester and in adults, it has a normal level of 2.5%. Haemoglobin A (α₂β₂) (PDB 1BZ0) - The most common type.

Haemoglobin F (α₂γ₂) (PDB 1FDH). Haemoglobin Portland (ξ₂γ₂). Gower 2 (α₂ε₂) (PDB 1A9W). Gower 1 (ξ₂ε₂).