Metabolism is the set of life-sustaining chemical reactions in organisms. The three main purposes of metabolism are: the conversion of food to energy to run cellular processes; these enzyme-catalyzed reactions allow organisms to grow and reproduce, maintain their structures, respond to their environments.. Metabolic reactions may be categorized as catabolic - the breaking down of compounds. Catabolism releases energy, anabolism consumes energy; the chemical reactions of metabolism are organized into metabolic pathways, in which one chemical is transformed through a series of steps into another chemical, each step being facilitated by a specific enzyme. Enzymes are crucial to metabolism because they allow organisms to drive desirable reactions that require energy that will not occur by themselves, by coupling them to spontaneous reactions that release energy. Enzymes act as catalysts - they allow a reaction to proceed more - and they allow the regulation of the rate of a metabolic reaction, for example in response to changes in the cell's environment or to signals from other cells.
The metabolic system of a particular organism determines which substances it will find nutritious and which poisonous. For example, some prokaryotes use hydrogen sulfide as a nutrient, yet this gas is poisonous to animals; the basal metabolic rate of an organism is the measure of the amount of energy consumed by all of these chemical reactions. A striking feature of metabolism is the similarity of the basic metabolic pathways among vastly different species. For example, the set of carboxylic acids that are best known as the intermediates in the citric acid cycle are present in all known organisms, being found in species as diverse as the unicellular bacterium Escherichia coli and huge multicellular organisms like elephants; these similarities in metabolic pathways are due to their early appearance in evolutionary history, their retention because of their efficacy. Most of the structures that make up animals and microbes are made from three basic classes of molecule: amino acids and lipids; as these molecules are vital for life, metabolic reactions either focus on making these molecules during the construction of cells and tissues, or by breaking them down and using them as a source of energy, by their digestion.
These biochemicals can be joined together to make polymers such as DNA and proteins, essential macromolecules of life. Proteins are made of amino acids arranged in a linear chain joined together by peptide bonds. Many proteins are enzymes. Other proteins have structural or mechanical functions, such as those that form the cytoskeleton, a system of scaffolding that maintains the cell shape. Proteins are important in cell signaling, immune responses, cell adhesion, active transport across membranes, the cell cycle. Amino acids contribute to cellular energy metabolism by providing a carbon source for entry into the citric acid cycle when a primary source of energy, such as glucose, is scarce, or when cells undergo metabolic stress. Lipids are the most diverse group of biochemicals, their main structural uses are as part of biological membranes both internal and external, such as the cell membrane, or as a source of energy. Lipids are defined as hydrophobic or amphipathic biological molecules but will dissolve in organic solvents such as benzene or chloroform.
The fats are a large group of compounds that contain fatty glycerol. Several variations on this basic structure exist, including alternate backbones such as sphingosine in the sphingolipids, hydrophilic groups such as phosphate as in phospholipids. Steroids such as cholesterol are another major class of lipids. Carbohydrates are aldehydes or ketones, with many hydroxyl groups attached, that can exist as straight chains or rings. Carbohydrates are the most abundant biological molecules, fill numerous roles, such as the storage and transport of energy and structural components; the basic carbohydrate units are called monosaccharides and include galactose and most glucose. Monosaccharides can be linked together to form polysaccharides in limitless ways; the two nucleic acids, DNA and RNA, are polymers of nucleotides. Each nucleotide is composed of a phosphate attached to a ribose or deoxyribose sugar group, attached to a nitrogenous base. Nucleic acids are critical for the storage and use of genetic information, its interpretation through the processes of transcription and protein biosynthesis.
This information is propagated through DNA replication. Many viruses have an RNA genome, such as HIV, which uses reverse transcription to create a DNA template from its viral RNA genome. RNA in ribozymes such as spliceosomes and ribosomes is similar to enzymes as it can catalyze chemical reactions. Individual nucleosides are made
The cell is the basic structural and biological unit of all known living organisms. A cell is the smallest unit of life. Cells are called the "building blocks of life"; the study of cells is called cellular biology. Cells consist of cytoplasm enclosed within a membrane, which contains many biomolecules such as proteins and nucleic acids. Organisms can be classified as multicellular; the number of cells in plants and animals varies from species to species, it has been estimated that humans contain somewhere around 40 trillion cells. Most plant and animal cells are visible only under a microscope, with dimensions between 1 and 100 micrometres. Cells were discovered by Robert Hooke in 1665, who named them for their resemblance to cells inhabited by Christian monks in a monastery. Cell theory, first developed in 1839 by Matthias Jakob Schleiden and Theodor Schwann, states that all organisms are composed of one or more cells, that cells are the fundamental unit of structure and function in all living organisms, that all cells come from pre-existing cells.
Cells emerged on Earth at least 3.5 billion years ago. Cells are of two types: eukaryotic, which contain a nucleus, prokaryotic, which do not. Prokaryotes are single-celled organisms, while eukaryotes can be either single-celled or multicellular. Prokaryotes include two of the three domains of life. Prokaryotic cells were the first form of life on Earth, characterised by having vital biological processes including cell signaling, they are simpler and smaller than eukaryotic cells, lack membrane-bound organelles such as a nucleus. The DNA of a prokaryotic cell consists of a single chromosome, in direct contact with the cytoplasm; the nuclear region in the cytoplasm is called the nucleoid. Most prokaryotes are the smallest of all organisms ranging from 0.5 to 2.0 µm in diameter. A prokaryotic cell has three architectural regions: Enclosing the cell is the cell envelope – consisting of a plasma membrane covered by a cell wall which, for some bacteria, may be further covered by a third layer called a capsule.
Though most prokaryotes have both a cell membrane and a cell wall, there are exceptions such as Mycoplasma and Thermoplasma which only possess the cell membrane layer. The envelope gives rigidity to the cell and separates the interior of the cell from its environment, serving as a protective filter; the cell wall consists of peptidoglycan in bacteria, acts as an additional barrier against exterior forces. It prevents the cell from expanding and bursting from osmotic pressure due to a hypotonic environment; some eukaryotic cells have a cell wall. Inside the cell is the cytoplasmic region that contains the genome and various sorts of inclusions; the genetic material is found in the cytoplasm. Prokaryotes can carry extrachromosomal DNA elements called plasmids, which are circular. Linear bacterial plasmids have been identified in several species of spirochete bacteria, including members of the genus Borrelia notably Borrelia burgdorferi, which causes Lyme disease. Though not forming a nucleus, the DNA is condensed in a nucleoid.
Plasmids encode additional genes, such as antibiotic resistance genes. On the outside and pili project from the cell's surface; these are structures made of proteins that facilitate communication between cells. Plants, fungi, slime moulds and algae are all eukaryotic; these cells are about fifteen times wider than a typical prokaryote and can be as much as a thousand times greater in volume. The main distinguishing feature of eukaryotes as compared to prokaryotes is compartmentalization: the presence of membrane-bound organelles in which specific activities take place. Most important among these is a cell nucleus, an organelle that houses the cell's DNA; this nucleus gives the eukaryote its name, which means "true kernel". Other differences include: The plasma membrane resembles that of prokaryotes in function, with minor differences in the setup. Cell walls may not be present; the eukaryotic DNA is organized in one or more linear molecules, called chromosomes, which are associated with histone proteins.
All chromosomal DNA is stored in the cell nucleus, separated from the cytoplasm by a membrane. Some eukaryotic organelles such as mitochondria contain some DNA. Many eukaryotic cells are ciliated with primary cilia. Primary cilia play important roles in chemosensation and thermosensation. Cilia may thus be "viewed as a sensory cellular antennae that coordinates a large number of cellular signaling pathways, sometimes coupling the signaling to ciliary motility or alternatively to cell division and differentiation." Motile eukaryotes can move using motile flagella. Motile cells are absent in flowering plants. Eukaryotic flagella are more complex than those of prokaryotes. All cells, whether prokaryotic or eukaryotic, have a membrane that envelops the cell, regulates what moves in and out, maintains the electric potential of the cell. Inside the membrane, the cytoplasm takes up most of the cell's volume. All cells possess DNA, the hereditary material of genes, RNA, containing the information necessary to build various proteins such as enzymes, the cell's primary machinery.
There are other kinds of biomolecules in cells. This article lists these primary cellular components briefly
Myoglobin is an iron- and oxygen-binding protein found in the muscle tissue of vertebrates in general and in all mammals. It is distantly related to hemoglobin, the iron- and oxygen-binding protein in blood in the red blood cells. In humans, myoglobin is only found in the bloodstream after muscle injury, it is an abnormal finding, can be diagnostically relevant when found in blood. Myoglobin is the primary oxygen-carrying pigment of muscle tissues. High concentrations of myoglobin in muscle cells allow organisms to hold their breath for a longer period of time. Diving mammals such as whales and seals have muscles with high abundance of myoglobin. Myoglobin is found in Type I muscle, Type II A and Type II B, but most texts consider myoglobin not to be found in smooth muscle. Myoglobin was the first protein to have its three-dimensional structure revealed by X-ray crystallography; this achievement was reported in 1958 by associates. For this discovery, John Kendrew shared the 1962 Nobel Prize in chemistry with Max Perutz.
Despite being one of the most studied proteins in biology, its physiological function is not yet conclusively established: mice genetically engineered to lack myoglobin can be viable and fertile but show many cellular and physiological adaptations to overcome the loss. Through observing these changes in myoglobin-deplete mice, it is hypothesised that myoglobin function relates to increased oxygen transport to muscle, oxygen storage and as a scavenger of reactive oxygen species. In humans myoglobin is encoded by the MB gene. Myoglobin can take the forms oxymyoglobin and metmyoglobin, analogously to hemoglobin taking the forms oxyhemoglobin, carboxyhemoglobin, methemoglobin. Like hemoglobin, myoglobin is a cytoplasmic protein, it harbors only one heme group. Although its heme group is identical to those in Hb, Mb has a higher affinity for oxygen than does hemoglobin; this difference is related to its different role: whereas hemoglobin transports oxygen, myoglobin's function is to store oxygen. Myoglobin contains hemes, pigments responsible for the colour of red meat.
The colour that meat takes is determined by the degree of oxidation of the myoglobin. In fresh meat the iron atom is in the ferrous oxidation state bound to an oxygen molecule. Meat cooked well done is brown because the iron atom is now in the ferric oxidation state, having lost an electron. If meat has been exposed to nitrites, it will remain pink because the iron atom is bound to NO, nitric oxide. Grilled meats can take on a pink "smoke ring" that comes from the iron binding to a molecule of carbon monoxide. Raw meat packed in a carbon monoxide atmosphere shows this same pink "smoke ring" due to the same principles. Notably, the surface of this raw meat displays the pink color, associated in consumers' minds with fresh meat; this artificially induced pink color can persist up to one year. Hormel and Cargill are both reported to use this meat-packing process, meat treated this way has been in the consumer market since 2003. Myoglobin is released from damaged muscle tissue, which has high concentrations of myoglobin.
The released myoglobin is filtered by the kidneys but is toxic to the renal tubular epithelium and so may cause acute kidney injury. It is not the myoglobin itself, toxic but the ferrihemate portion, dissociated from myoglobin in acidic environments. Myoglobin is a sensitive marker for muscle injury, making it a potential marker for heart attack in patients with chest pain. However, elevated myoglobin has low specificity for acute myocardial infarction and thus CK-MB, cardiac Troponin, ECG, clinical signs should be taken into account to make the diagnosis. Myoglobin belongs to the globin superfamily of proteins, as with other globins, consists of eight alpha helices connected by loops. Myoglobin contains 154 amino acids. Myoglobin contains a porphyrin ring with an iron at its center. A proximal histidine group is attached directly to iron, a distal histidine group hovers near the opposite face; the distal imidazole is not bonded to the iron but is available to interact with the substrate O2. This interaction encourages the binding of O2, but not carbon monoxide, which still binds about 240× more than O2.
The binding of O2 causes substantial structural change at the Fe center, which shrinks in radius and moves into the center of N4 pocket. O2-binding induces "spin-pairing": the five-coordinate ferrous deoxy form is high spin and the six coordinate oxy form is low spin and diamagnetic. Many models of myoglobin have been synthesized as part of a broad interest in transition metal dioxygen complexes. A well known example is the picket fence porphyrin, which consists of a ferrous complex of a sterically bulky derivative of tetraphenylporphyrin. In the presence of an imidazole ligand, this ferrous complex reversibly binds O2; the O2 substrate adopts a bent geometry. A key property of this model is the slow formation of the μ-oxo dimer, an inactive diferric state. In nature, such deactivation pathways are suppressed by protein matrix that prevents close approach of the Fe-porphyrin assemblies. Cytoglobin Hemoglobin Hemoprotein Neuroglobin Phytoglobin Myoglobinuria - The presence of myoglobin in the urine Ischemia-reperfusion injury of the appendicular musculoskeletal system Online Mendelian Inheritance in Man 160000 human genetics The Myoglobin Protein Protein Database featured mole
OCLC Online Computer Library Center, Incorporated d/b/a OCLC is an American nonprofit cooperative organization "dedicated to the public purposes of furthering access to the world's information and reducing information costs". It was founded in 1967 as the Ohio College Library Center. OCLC and its member libraries cooperatively produce and maintain WorldCat, the largest online public access catalog in the world. OCLC is funded by the fees that libraries have to pay for its services. OCLC maintains the Dewey Decimal Classification system. OCLC began in 1967, as the Ohio College Library Center, through a collaboration of university presidents, vice presidents, library directors who wanted to create a cooperative computerized network for libraries in the state of Ohio; the group first met on July 5, 1967 on the campus of the Ohio State University to sign the articles of incorporation for the nonprofit organization, hired Frederick G. Kilgour, a former Yale University medical school librarian, to design the shared cataloging system.
Kilgour wished to merge the latest information storage and retrieval system of the time, the computer, with the oldest, the library. The plan was to merge the catalogs of Ohio libraries electronically through a computer network and database to streamline operations, control costs, increase efficiency in library management, bringing libraries together to cooperatively keep track of the world's information in order to best serve researchers and scholars; the first library to do online cataloging through OCLC was the Alden Library at Ohio University on August 26, 1971. This was the first online cataloging by any library worldwide. Membership in OCLC is based on use of services and contribution of data. Between 1967 and 1977, OCLC membership was limited to institutions in Ohio, but in 1978, a new governance structure was established that allowed institutions from other states to join. In 2002, the governance structure was again modified to accommodate participation from outside the United States.
As OCLC expanded services in the United States outside Ohio, it relied on establishing strategic partnerships with "networks", organizations that provided training and marketing services. By 2008, there were 15 independent United States regional service providers. OCLC networks played a key role in OCLC governance, with networks electing delegates to serve on the OCLC Members Council. During 2008, OCLC commissioned two studies to look at distribution channels. In early 2009, OCLC negotiated new contracts with the former networks and opened a centralized support center. OCLC provides bibliographic and full-text information to anyone. OCLC and its member libraries cooperatively produce and maintain WorldCat—the OCLC Online Union Catalog, the largest online public access catalog in the world. WorldCat has holding records from private libraries worldwide; the Open WorldCat program, launched in late 2003, exposed a subset of WorldCat records to Web users via popular Internet search and bookselling sites.
In October 2005, the OCLC technical staff began a wiki project, WikiD, allowing readers to add commentary and structured-field information associated with any WorldCat record. WikiD was phased out; the Online Computer Library Center acquired the trademark and copyrights associated with the Dewey Decimal Classification System when it bought Forest Press in 1988. A browser for books with their Dewey Decimal Classifications was available until July 2013; until August 2009, when it was sold to Backstage Library Works, OCLC owned a preservation microfilm and digitization operation called the OCLC Preservation Service Center, with its principal office in Bethlehem, Pennsylvania. The reference management service QuestionPoint provides libraries with tools to communicate with users; this around-the-clock reference service is provided by a cooperative of participating global libraries. Starting in 1971, OCLC produced catalog cards for members alongside its shared online catalog. OCLC commercially sells software, such as CONTENTdm for managing digital collections.
It offers the bibliographic discovery system WorldCat Discovery, which allows for library patrons to use a single search interface to access an institution's catalog, database subscriptions and more. OCLC has been conducting research for the library community for more than 30 years. In accordance with its mission, OCLC makes its research outcomes known through various publications; these publications, including journal articles, reports and presentations, are available through the organization's website. OCLC Publications – Research articles from various journals including Code4Lib Journal, OCLC Research, Reference & User Services Quarterly, College & Research Libraries News, Art Libraries Journal, National Education Association Newsletter; the most recent publications are displayed first, all archived resources, starting in 1970, are available. Membership Reports – A number of significant reports on topics ranging from virtual reference in libraries to perceptions about library funding. Newsletters – Current and archived newsletters for the library and archive community.
Presentations – Presentations from both guest speakers and OCLC research from conferences and other events. The presentations are organized into five categories: Conference presentations, Dewey presentations, Distinguished Seminar Series, Guest presentations, Research staff
Heavy metals are defined as metals with high densities, atomic weights, or atomic numbers. The criteria used, whether metalloids are included, vary depending on the author and context. In metallurgy, for example, a heavy metal may be defined on the basis of density, whereas in physics the distinguishing criterion might be atomic number, while a chemist would be more concerned with chemical behaviour. More specific definitions have been published, but none of these have been accepted; the definitions surveyed in this article encompass up to 96 out of the 118 known chemical elements. Despite this lack of agreement, the term is used in science. A density of more than 5 g/cm3 is sometimes quoted as a used criterion and is used in the body of this article; the earliest known metals—common metals such as iron and tin, precious metals such as silver and platinum—are heavy metals. From 1809 onwards, light metals, such as magnesium and titanium, were discovered, as well as less well-known heavy metals including gallium and hafnium.
Some heavy metals are either essential nutrients, or harmless, but can be toxic in larger amounts or certain forms. Other heavy metals, such as cadmium and lead, are poisonous. Potential sources of heavy metal poisoning include mining, industrial wastes, agricultural runoff, occupational exposure and treated timber. Physical and chemical characterisations of heavy metals need to be treated with caution, as the metals involved are not always defined; as well as being dense, heavy metals tend to be less reactive than lighter metals and have much less soluble sulfides and hydroxides. While it is easy to distinguish a heavy metal such as tungsten from a lighter metal such as sodium, a few heavy metals, such as zinc and lead, have some of the characteristics of lighter metals, lighter metals such as beryllium and titanium, have some of the characteristics of heavier metals. Heavy metals are scarce in the Earth's crust but are present in many aspects of modern life, they are used in, for example, golf clubs, antiseptics, self-cleaning ovens, solar panels, mobile phones, particle accelerators.
There is no agreed criterion-based definition of a heavy metal. Different meanings may be attached depending on the context. In metallurgy, for example, a heavy metal may be defined on the basis of density, whereas in physics the distinguishing criterion might be atomic number, a chemist would be more concerned with chemical behaviour. Density criteria range from above 3.5 g/cm3 to above 7 g/cm3. Atomic weight definitions can range from greater than sodium. Atomic numbers of heavy metals are given as greater than 20. Definitions based on atomic number have been criticised for including metals with low densities. For example, rubidium in group 1 of the periodic table has an atomic number of 37 but a density of only 1.532 g/cm3, below the threshold figure used by other authors. The same problem may occur with atomic weight based definitions; the United States Pharmacopeia includes a test for heavy metals that involves precipitating metallic impurities as their coloured sulfides." In 1997, Stephen Hawkes, a chemistry professor writing in the context of fifty years' experience with the term, said it applied to "metals with insoluble sulfides and hydroxides, whose salts produce colored solutions in water and whose complexes are colored".
On the basis of the metals he had seen referred to as heavy metals, he suggested it would useful to define them as all the metals in periodic table columns 3 to 16 that are in row 4 or greater, in other words, the transition metals and post-transition metals. The lanthanides satisfy Hawkes' three-part description. In biochemistry, heavy metals are sometimes defined—on the basis of the Lewis acid behaviour of their ions in aqueous solution—as class B and borderline metals. In this scheme, class A metal ions prefer oxygen donors. Class A metals, which tend to have low electronegativity and form bonds with large ionic character, are the alkali and alkaline earths, the group 3 metals, the lanthanides and actinides. Class B metals, which tend to have higher electronegativity and form bonds with considerable covalent character, are the heavier transition and post-transition metals. Borderline metals comprise the lighter transition and post-transition metals; the distinction between the class A metals and the other two categories is sharp.
A cited proposal to use these classification categories instead of the more evocative name heavy metal has not been adopted. A density of more than 5 g/cm3 is sometimes mentioned as a common heavy metal defining factor and, in the absence of a unanimous definition, is used to populate this list and guide the remainder of the article. Metalloids meeting the applicable criteria–arsenic and antimony for example—are sometimes counted as heavy metals in environmental chemistry, as is the case here. Selenium is include
Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the outer surfaces of organs and blood vessels throughout the body, as well as the inner surfaces of cavities in many internal organs. An example is the outermost layer of the skin. There are three principal shapes of epithelial cell: squamous and cuboidal; these can be arranged in a single layer of cells as simple epithelium, either squamous, columnar, or cuboidal, or in layers of two or more cells deep as stratified, either squamous, columnar or cuboidal. In some tissues, a layer of columnar cells may appear to be stratified due to the placement of the nuclei; this sort of tissue is called pseudostratified. All glands are made up of epithelial cells. Functions of epithelial cells include secretion, selective absorption, transcellular transport, sensing. Epithelial layers contain no blood vessels, so they must receive nourishment via diffusion of substances from the underlying connective tissue, through the basement membrane.
Cell junctions are well employed in epithelial tissues. In general, epithelial tissues are classified by the number of their layers and by the shape and function of the cells; the three principal shapes associated with epithelial cells are—squamous and columnar. Squamous epithelium has cells; this is found as the lining of the mouth, the blood vessels and in the alveoli of the lungs. Cuboidal epithelium has cells whose height and width are the same. Columnar epithelium has cells taller. By layer, epithelium is classed as either simple epithelium, only one cell thick or stratified epithelium having two or more cells in thickness or multi-layered – as stratified squamous epithelium, stratified cuboidal epithelium, stratified columnar epithelium, both types of layering can be made up of any of the cell shapes. However, when taller simple columnar epithelial cells are viewed in cross section showing several nuclei appearing at different heights, they can be confused with stratified epithelia; this kind of epithelium is therefore described as pseudostratified columnar epithelium.
Transitional epithelium has cells that can change from squamous to cuboidal, depending on the amount of tension on the epithelium. Simple epithelium is a single layer of cells with every cell in direct contact with the basement membrane that separates it from the underlying connective tissue. In general, it is found where filtration occur; the thinness of the epithelial barrier facilitates these processes. In general, simple epithelial tissues are classified by the shape of their cells; the four major classes of simple epithelium are: simple squamous. Simple squamous. Simple cuboidal: these cells may have secretory, absorptive, or excretory functions. Examples include small collecting ducts of kidney and salivary gland. Simple columnar. Non-ciliated epithelium can possess microvilli; some tissues are referred to as simple glandular columnar epithelium. These secrete mucus and are found in stomach and rectum. Pseudostratified columnar epithelium; the ciliated type is called respiratory epithelium as it is exclusively confined to the larger respiratory airways of the nasal cavity and bronchi.
Stratified epithelium differs from simple epithelium. It is therefore found where body linings have to withstand mechanical or chemical insult such that layers can be abraded and lost without exposing subepithelial layers. Cells flatten as the layers become more apical, though in their most basal layers the cells can be squamous, cuboidal or columnar. Stratified epithelia can have the following specializations: The basic cell types are squamous and columnar classed by their shape. Cells of epithelial tissue are scutoid shaped packed and form a continuous sheet, they have no intercellular spaces. All epithelia is separated from underlying tissues by an extracellular fibrous basement membrane; the lining of the mouth, lung alveoli and kidney tubules are all made of epithelial tissue. The lining of the blood and lymphatic vessels are of a specialised form of epithelium called endothelium. Epithelium lines both the outside and the inside cavities and lumina of bodies; the outermost layer of human skin is composed of dead stratified squamous, keratinized epithelial cells.
Tissues that line the inside of the mouth, the esophagus, the vagina, part of the rectum are composed of nonkeratinized stratified squamous epithelium. Other surfaces that separate body cavities from the outside environment are lined by simple squamous, columnar, or pseudostratified epithelial cells. Other epithelial cells line the insides of the lungs, the gastrointestinal tract, the reproductive and urinary tracts, make up the exocrine and endocrine glands; the outer surface of the cornea is covered with fast-growing regenerated epithelial cells. A specialised form of epithelium – endothelium forms the inner lining of blood vessels and the heart, is known as vascular endotheliu
Hemoglobin or haemoglobin, abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates as well as the tissues of some invertebrates. Haemoglobin in the blood carries oxygen from the gills to the rest of the body. There it releases the oxygen to permit aerobic respiration to provide energy to power the functions of the organism in the process called metabolism. A healthy individual has 12 to 16 grams of haemoglobin in every 100 ml of blood. In mammals, the protein makes up about 96% of the red blood cells' dry content, around 35% of the total content. Haemoglobin has an oxygen-binding capacity of 1.34 mL O2 per gram, which increases the total blood oxygen capacity seventy-fold compared to dissolved oxygen in blood. The mammalian hemoglobin molecule can bind up to four oxygen molecules. Hemoglobin is involved in the transport of other gases: It carries some of the body's respiratory carbon dioxide as carbaminohemoglobin, in which CO2 is bound to the heme protein.
The molecule carries the important regulatory molecule nitric oxide bound to a globin protein thiol group, releasing it at the same time as oxygen. Haemoglobin is found outside red blood cells and their progenitor lines. Other cells that contain haemoglobin include the A9 dopaminergic neurons in the substantia nigra, alveolar cells, retinal pigment epithelium, mesangial cells in the kidney, endometrial cells, cervical cells and vaginal epithelial cells. In these tissues, haemoglobin has a non-oxygen-carrying function as an antioxidant and a regulator of iron metabolism. Haemoglobin and haemoglobin-like molecules are found in many invertebrates and plants. In these organisms, haemoglobins may carry oxygen, or they may act to transport and regulate other small molecules and ions such as carbon dioxide, nitric oxide, hydrogen sulfide and sulfide. A variant of the molecule, called leghaemoglobin, is used to scavenge oxygen away from anaerobic systems, such as the nitrogen-fixing nodules of leguminous plants, before the oxygen can poison the system.
In 1825 J. F. Engelhard 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 n × 16000, the first determination of a protein's molecular mass; this "hasty conclusion" drew a lot of ridicule at the time from scientists who could not believe that any molecule could be that big. Gilbert Smithson Adair confirmed Engelhard's results in 1925 by measuring the osmotic pressure of hemoglobin solutions; the oxygen-carrying property of hemoglobin was discovered by Hünefeld in 1840. In 1851, German physiologist Otto Funke published a series of articles in which he described growing hemoglobin crystals by successively diluting red blood cells with a solvent such as pure water, alcohol or ether, followed by slow evaporation of the solvent from the resulting protein solution. Hemoglobin's reversible oxygenation was described a few years by Felix Hoppe-Seyler. In 1959, Max Perutz determined the molecular structure of hemoglobin by X-ray crystallography.
This work resulted in his sharing with John Kendrew the 1962 Nobel Prize in Chemistry for their studies of the structures of globular proteins. The role of hemoglobin in the blood was elucidated by French physiologist Claude Bernard; the name hemoglobin is derived from the words heme and globin, reflecting the fact that each subunit of hemoglobin is a globular protein with an embedded heme 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. Hemoglobin consists of protein subunits, these proteins, in turn, are folded chains of a large number of different amino acids called polypeptides; the amino acid sequence of any polypeptide created by a cell is in turn determined by the stretches of DNA called genes. In all proteins, it is the amino acid sequence that determines the protein's chemical properties and function. There is more than one hemoglobin gene: in humans, hemoglobin A is coded for by the genes, HBA1, HBA2, HBB.
The amino acid sequences of the globin proteins in hemoglobins differ between species. These differences grow with evolutionary distance between species. For example, the most common hemoglobin sequences in humans and chimpanzees are nearly identical, differing by only one amino acid in both the alpha and the beta globin protein chains; these differences grow larger between less related species. Within a species, different variants of hemoglobin always exist, although one sequence is a "most common" one in each species. Mutations in the genes for the hemoglobin protein in a species result in hemoglobin variants. Many of these mutant forms of hemoglobin cause no disease; some of these mutant forms of hemoglobin, cause a group of hereditary diseases termed the hemoglobinopathies. The best known hemoglobinopathy is sickle-cell disease, the first human disease whose mechanism was understood at the molecular level. A separate set of diseases called thalassemias involves underproduction of normal and sometimes abnormal hemoglobins, through problems and mutations in globin gene regulation.
All these diseases produce anemia. Variations in hemoglobin amino acid sequences, as with other proteins, may be adaptive. For example, hemoglobin has been found to adapt in different ways to