Glycogen debranching enzyme
A debranching enzyme is a molecule that helps facilitate the breakdown of glycogen, which serves as a store of glucose in the body, through glucosyltransferase and glucosidase activity. Together with phosphorylases, debranching enzymes mobilize glucose reserves from glycogen deposits in the muscles and liver; this constitutes a major source of energy reserves in most organisms. Glycogen breakdown is regulated in the body in the liver, by various hormones including insulin and glucagon, to maintain a homeostatic balance of blood-glucose levels; when glycogen breakdown is compromised by mutations in the glycogen debranching enzyme, metabolic diseases such as Glycogen storage disease type III can result. Glucosyltransferase and glucosidase are performed by a single enzyme in mammals and some bacteria, but by two distinct enzymes in E. coli and other bacteria, complicating nomenclature. Proteins that catalyze both functions are referred to as glycogen debranching enzymes; when glucosyltransferase and glucosidase are catalyzed by distinct enzymes, "glycogen debranching enzyme" refers to the glucosidase enzyme.
In some literature, an enzyme capable only of glucosidase is referred to as a "debranching enzyme". Together with phosphorylase, glycogen debranching enzymes function in glycogen breakdown and glucose mobilization; when phosphorylase has digested a glycogen branch down to four glucose residues, it will not remove further residues. Glycogen debranching enzymes assist phosphorylase, the primary enzyme involved in glycogen breakdown, mobilize glycogen stores. Phosphorylase can only cleave α-1,4- glycosidic bond between adjacent glucose molecules in glycogen but branches exist as α-1,6 linkages; when phosphorylase reaches four residues from a branching point it stops cleaving. Before phosphorylase can resume catabolism, debranching enzymes perform two functions: 4-α-D-glucanotransferase, or glucosyltransferase, transfers three glucose residues from the four-residue glycogen branch to a nearby branch; this exposes a single glucose residue joined to the glucose chain through an α -1,6 glycosidic linkage Amylo-α-1,6-glucosidase, or glucosidase, cleaves the remaining alpha-1,6 linkage, producing glucose and a linear chain of glycogen.
The mechanism by which the glucosidase cleaves the α -1,6-linkage is not known because the amino acids in the active site have not yet been identified. It is thought to proceed through a two step acid base assistance type mechanism, with an oxocarbenium ion intermediate, retention of configuration in glucose; this is a common method through which to cleave bonds, with an acid below the site of hydrolysis to lend a proton and a base above to deprotinate a water which can act as a nucleophile. These acids and bases are amino acid side chains in the active site of the enzyme. A scheme for the mechanism is shown in the figure below, thus the debranching enzymes, transferase and α-1,6- glucosidase converts the branched glycogen structure into a linear one, paving the way for further cleavage by phosphorylase. In E. coli and other bacteria, glucosyltransferase and glucosidase functions are performed by two distinct enzymes. In E. coli, Glucose transfer is performed by 4-alpha-glucanotransferase, a 78.5 kDa protein coded for by the gene malQ.
A second protein, referred to as debranching enzyme, performs α-1,6-glucose cleavage. This enzyme has a molecular mass of 73.6 kDa, is coded for by the gene glgX. Activity of the two enzymes is not always coupled. In E. coli glgX selectively catalyzes the cleavage of 4-subunit branches, without the action of glucanotransferase. The product of this cleavage, maltotetraose, is further degraded by maltodextrin phosphorylase. E. Coli GlgX is structurally similar to the protein isoamylase; the monomeric protein contains a central domain in which eight parallel beta-strands are surrounded by eight parallel alpha strands. Notable within this structure is a groove 26 angstroms long and 9 angstroms wide, containing aromatic residues that are thought to stabilize a four-glucose branch before cleavage; the glycogen-degrading enzyme of the archaea Sulfolobus solfataricus, treX, provides an interesting example of using a single active site for two activities: amylosidase and glucanotransferase activities. TreX is structurally similar to glgX, has a mass of 80kD and one active site.
Unlike either glgX, treX exists as a dimer and tetramer in solution. TreX's oligomeric form seems to play a significant role in altering both enzyme function. Dimerization is thought to stabilize a "flexible loop" located close to the active site; this may be key to explaining. As a tetramer, the catalytic efficiency of treX is increased fourfold over its dimeric form. In mammals and yeast, a single enzyme performs both debranching functions; the human glycogen debranching enzyme is a monomer with a molecular weight of 175 kDa. It has been shown that the two catalytic actions of AGL can function independently of each other, demonstrating that multiple active sites are present; this idea has been reinforced with inhibitors of the active site, such as polyhydroxyamine, which were found to inhibit glucosidase activity while transferase activity was not measurably changed. Glycogen debranching enzyme is the only known eukaryotic enzyme that contains multiple catalytic sites and is active as a monomer.
Some studies have shown that the C-terminal half of yeast GDE is associated with glucosidase activity, while the N-terminal half is associated with glucosyltransferase activity. In addition to these two active sites, AGL appears to contain a third active site tha
Hydrolysis is a term used for both an electro-chemical process and a biological one. The hydrolysis of water is the separation of water molecules into hydrogen and oxygen atoms using electricity. Biological hydrolysis is the cleavage of biomolecules where a water molecule is consumed to effect the separation of a larger molecule into component parts; when a carbohydrate is broken into its component sugar molecules by hydrolysis, this is termed saccharification. Hydrolysis or saccharification is a step in the degradation of a substance. Hydrolysis can be the reverse of a condensation reaction in which two molecules join together into a larger one and eject a water molecule, thus hydrolysis adds water to break down, whereas condensation builds up by removing water and any other solvents. Some hydration reactions are hydrolysis. Hydrolysis is a chemical process in which a molecule of water is added to a substance. Sometimes this addition causes both water molecule to split into two parts. In such reactions, one fragment of the target molecule gains a hydrogen ion.
It breaks a chemical bond in the compound. A common kind of hydrolysis occurs when a salt of weak base is dissolved in water. Water spontaneously ionizes into hydroxide anions and hydronium cations; the salt dissociates into its constituent anions and cations. For example, sodium acetate dissociates in water into acetate ions. Sodium ions react little with the hydroxide ions whereas the acetate ions combine with hydronium ions to produce acetic acid. In this case the net result is a relative excess of hydroxide ions. Strong acids undergo hydrolysis. For example, dissolving sulfuric acid in water is accompanied by hydrolysis to give hydronium and bisulfate, the sulfuric acid's conjugate base. For a more technical discussion of what occurs during such a hydrolysis, see Brønsted–Lowry acid–base theory. Acid–base-catalysed hydrolyses are common, their hydrolysis occurs when the nucleophile attacks the carbon of the carbonyl group of the ester or amide. In an aqueous base, hydroxyl ions are better nucleophiles than polar molecules such as water.
In acids, the carbonyl group becomes protonated, this leads to a much easier nucleophilic attack. The products for both hydrolyses are compounds with carboxylic acid groups; the oldest commercially practiced example of ester hydrolysis is saponification. It is the hydrolysis of a triglyceride with an aqueous base such as sodium hydroxide. During the process, glycerol is formed, the fatty acids react with the base, converting them to salts; these salts are called soaps used in households. In addition, in living systems, most biochemical reactions take place during the catalysis of enzymes; the catalytic action of enzymes allows the hydrolysis of proteins, fats and carbohydrates. As an example, one may consider proteases, they catalyse the hydrolysis of interior peptide bonds in peptide chains, as opposed to exopeptidases. However, proteases do not catalyse the hydrolysis of all kinds of proteins, their action is stereo-selective: Only proteins with a certain tertiary structure are targeted as some kind of orienting force is needed to place the amide group in the proper position for catalysis.
The necessary contacts between an enzyme and its substrates are created because the enzyme folds in such a way as to form a crevice into which the substrate fits. Therefore, proteins that do not fit into the crevice will not undergo hydrolysis; this specificity preserves the integrity of other proteins such as hormones, therefore the biological system continues to function normally. Upon hydrolysis, an amide converts into an amine or ammonia. One of the two oxygen groups on the carboxylic acid are derived from a water molecule and the amine gains the hydrogen ion; the hydrolysis of peptides gives amino acids. Many polyamide polymers such as nylon 6,6 hydrolyse in the presence of strong acids; the process leads to depolymerization. For this reason nylon products fail by fracturing. Polyesters are susceptible to similar polymer degradation reactions; the problem is known as environmental stress cracking. Hydrolysis is related to energy storage. All living cells require a continual supply of energy for two main purposes: the biosynthesis of micro and macromolecules, the active transport of ions and molecules across cell membranes.
The energy derived from the oxidation of nutrients is not used directly but, by means of a complex and long sequence of reactions, it is channelled into a special energy-storage molecule, adenosine triphosphate. The ATP molecule contains pyrophosphate linkages. ATP can undergo hydrolysis in two ways: the removal of terminal phosphate to form adenosine diphosphate and inorganic phosphate, or the removal of a terminal diphosphate to yield adenosine monophosphate and pyrophosphate; the latter undergoes further cleavage in
The cytosol known as intracellular fluid or cytoplasmic matrix, is the liquid found inside cells. It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into many compartments. In the eukaryotic cell, the cytosol is surrounded by the cell membrane and is part of the cytoplasm, which comprises the mitochondria and other organelles; the cytosol is thus a liquid matrix around the organelles. In prokaryotes, most of the chemical reactions of metabolism take place in the cytosol, while a few take place in membranes or in the periplasmic space. In eukaryotes, while many metabolic pathways still occur in the cytosol, others take place within organelles; the cytosol is a complex mixture of substances dissolved in water. Although water forms the large majority of the cytosol, its structure and properties within cells is not well understood; the concentrations of ions such as sodium and potassium are different in the cytosol than in the extracellular fluid.
The cytosol contains large amounts of macromolecules, which can alter how molecules behave, through macromolecular crowding. Although it was once thought to be a simple solution of molecules, the cytosol has multiple levels of organization; these include concentration gradients of small molecules such as calcium, large complexes of enzymes that act together and take part in metabolic pathways, protein complexes such as proteasomes and carboxysomes that enclose and separate parts of the cytosol. The term "cytosol" was first introduced in 1965 by H. A. Lardy, referred to the liquid, produced by breaking cells apart and pelleting all the insoluble components by ultracentrifugation; such a soluble cell extract is not identical to the soluble part of the cell cytoplasm and is called a cytoplasmic fraction. The term cytosol is now used to refer to the liquid phase of the cytoplasm in an intact cell; this excludes any part of the cytoplasm, contained within organelles. Due to the possibility of confusion between the use of the word "cytosol" to refer to both extracts of cells and the soluble part of the cytoplasm in intact cells, the phrase "aqueous cytoplasm" has been used to describe the liquid contents of the cytoplasm of living cells.
Prior to this, other terms, including "hyaloplasm", were used for the cell fluid, not always synonymously, as its nature was not clear. The proportion of cell volume, cytosol varies: for example while this compartment forms the bulk of cell structure in bacteria, in plant cells the main compartment is the large central vacuole; the cytosol consists of water, dissolved ions, small molecules, large water-soluble molecules. The majority of these non-protein molecules have a molecular mass of less than 300 Da; this mixture of small molecules is extraordinarily complex, as the variety of molecules that are involved in metabolism is immense. For example, up to 200,000 different small molecules might be made in plants, although not all these will be present in the same species, or in a single cell. Estimates of the number of metabolites in single cells such as E. coli and baker's yeast predict that under 1,000 are made. Most of the cytosol is water; the pH of the intracellular fluid is 7.4. While human cytosolic pH ranges between 7.0 - 7.4, is higher if a cell is growing.
The viscosity of cytoplasm is the same as pure water, although diffusion of small molecules through this liquid is about fourfold slower than in pure water, due to collisions with the large numbers of macromolecules in the cytosol. Studies in the brine shrimp have examined. Although water is vital for life, the structure of this water in the cytosol is not well understood because methods such as nuclear magnetic resonance spectroscopy only give information on the average structure of water, cannot measure local variations at the microscopic scale; the structure of pure water is poorly understood, due to the ability of water to form structures such as water clusters through hydrogen bonds. The classic view of water in cells is that about 5% of this water is bound in by solutes or macromolecules as water of solvation, while the majority has the same structure as pure water; this water of solvation is not active in osmosis and may have different solvent properties, so that some dissolved molecules are excluded, while others become concentrated.
However, others argue that the effects of the high concentrations of macromolecules in cells extend throughout the cytosol and that water in cells behaves differently from the water in dilute solutions. These ideas include the proposal that cells contain zones of low and high-density water, which could have widespread effects on the structures and functions of the other parts of the cell. However, the use of advanced nuclear magnetic resonance methods to directly measure the mobility of water in living cells contradicts this idea, as it suggests that 85% of cell water acts like that pure water, while the remainder is less mobile and bound to macromolecules; the concentrations of the other ions in cytosol are quite different from those in extracellular flui
Carl Ferdinand Cori
Carl Ferdinand Cori, ForMemRS was a Czech-American biochemist and pharmacologist born in Prague who, together with his wife Gerty Cori and Argentine physiologist Bernardo Houssay, received a Nobel Prize in 1947 for their discovery of how glycogen – a derivative of glucose – is broken down and resynthesized in the body, for use as a store and source of energy. In 2004, both were designated a National Historic Chemical Landmark in recognition of their work that elucidated carbohydrate metabolism. Carl was the son of Carl Isidor Cori, a zoologist, Maria née Lippich, a daughter of the Italian-Bohemian/Austrian physician Ferdinand Lippich; the Cori Family came from the Papal State to the Royal Bohemian Crownland,(Monarchical Austria at the end of the 17th century. Carl Ferdinand's grandfather Eduard Cori was an administrative officer and beekeeper in Brüx, grandmother was Rosina Trinks. Carl Ferdinand's younger sister Margarete Cori was a lecturer of Prague and the wife of the Bohemian geneticist Felix Mainx.
He grew up in Trieste, where his father Carl Isidor was the director of the Marine Biological Station. In late 1914 the Cori family moved to Prague and Carl entered the medical school of Charles University in Prague. While studying there he met Gerty Theresa Radnitz, he was drafted into the Austro-Hungarian Army and served in the ski corps, was transferred to the sanitary corps, for which he set up a laboratory in Trieste. At the end of the war Carl completed his studies, graduating with Gerty in 1920. Carl and Gerty worked together in clinics in Vienna, their only child, married Anne, a daughter of the American constitutional lawyer and anti-feminist Phyllis Schlafly. Carl was invited to Graz to work with Otto Loewi to study the effect of the vagus nerve on the heart. While Carl was in Graz, Gerty remained in Vienna. A year Carl was offered a position at the State Institute for the Study of Malignant Diseases in Buffalo, New York and the Cori's moved to Buffalo. In 1928, they became naturalized citizens of the United States.
While at the Institute the Coris’ research focused on carbohydrate metabolism, leading to the definition of the Cori cycle in 1929. In 1931, Carl accepted a position at the Washington University School of Medicine in St. Louis, Missouri. Carl joined. In St. Louis, the Cori's continued their research on glycogen and glucose and began to describe glycogenolysis and synthesizing the important enzyme glycogen phosphorylase. For these discoveries, they received the Nobel Prize in Physiology or Medicine in 1947. Gerty died in 1957 and Carl married Anne Fitzgerald-Jones in 1960, he stayed on at Washington University until 1966, when he retired as chair of the biochemistry department. He was appointed visiting professor of Biological Chemistry at Harvard University while maintaining a laboratory space at the Massachusetts General Hospital, where he pursued research in genetics. From 1968 to 1983, he collaborated with noted geneticist Salomé Glüecksohn-Waelsch of the Albert Einstein College of Medicine in New York, until the 1980s when illness prevented him from continuing.
In 1976, Carl received the Laurea honoris causa in Medicine from the University of Trieste. Carl shares a star with Gerty on the St. Louis Walk of Fame. In addition to winning the Nobel Prize, Cori won the Albert Lasker Award for Basic Medical Research in 1946 and in 1959, the Austrian Decoration for Science and Art. Cori was elected a Foreign Member of the Royal Society in 1950 and the Carl Cori Endowed Professorship at Washington University is named in his honor held by Colin Nichols
Deoxyribonucleic acid is a molecule composed of two chains that coil around each other to form a double helix carrying the genetic instructions used in the growth, development and reproduction of all known organisms and many viruses. DNA and ribonucleic acid are nucleic acids; the two DNA strands are known as polynucleotides as they are composed of simpler monomeric units called nucleotides. Each nucleotide is composed of one of four nitrogen-containing nucleobases, a sugar called deoxyribose, a phosphate group; the nucleotides are joined to one another in a chain by covalent bonds between the sugar of one nucleotide and the phosphate of the next, resulting in an alternating sugar-phosphate backbone. The nitrogenous bases of the two separate polynucleotide strands are bound together, according to base pairing rules, with hydrogen bonds to make double-stranded DNA; the complementary nitrogenous bases are divided into two groups and purines. In DNA, the pyrimidines are cytosine. Both strands of double-stranded DNA store the same biological information.
This information is replicated as and when the two strands separate. A large part of DNA is non-coding, meaning that these sections do not serve as patterns for protein sequences; the two strands of DNA are thus antiparallel. Attached to each sugar is one of four types of nucleobases, it is the sequence of these four nucleobases along the backbone. RNA strands are created using DNA strands as a template in a process called transcription. Under the genetic code, these RNA strands specify the sequence of amino acids within proteins in a process called translation. Within eukaryotic cells, DNA is organized into long structures called chromosomes. Before typical cell division, these chromosomes are duplicated in the process of DNA replication, providing a complete set of chromosomes for each daughter cell. Eukaryotic organisms store most of their DNA inside the cell nucleus as nuclear DNA, some in the mitochondria as mitochondrial DNA, or in chloroplasts as chloroplast DNA. In contrast, prokaryotes store their DNA only in circular chromosomes.
Within eukaryotic chromosomes, chromatin proteins, such as histones and organize DNA. These compacting structures guide the interactions between DNA and other proteins, helping control which parts of the DNA are transcribed. DNA was first isolated by Friedrich Miescher in 1869, its molecular structure was first identified by Francis Crick and James Watson at the Cavendish Laboratory within the University of Cambridge in 1953, whose model-building efforts were guided by X-ray diffraction data acquired by Raymond Gosling, a post-graduate student of Rosalind Franklin. DNA is used by researchers as a molecular tool to explore physical laws and theories, such as the ergodic theorem and the theory of elasticity; the unique material properties of DNA have made it an attractive molecule for material scientists and engineers interested in micro- and nano-fabrication. Among notable advances in this field are DNA origami and DNA-based hybrid materials. DNA is a long polymer made from repeating units called nucleotides.
The structure of DNA is dynamic along its length, being capable of coiling into tight loops and other shapes. In all species it is composed of two helical chains, bound to each other by hydrogen bonds. Both chains are coiled around the same axis, have the same pitch of 34 angstroms; the pair of chains has a radius of 10 angstroms. According to another study, when measured in a different solution, the DNA chain measured 22 to 26 angstroms wide, one nucleotide unit measured 3.3 Å long. Although each individual nucleotide is small, a DNA polymer can be large and contain hundreds of millions, such as in chromosome 1. Chromosome 1 is the largest human chromosome with 220 million base pairs, would be 85 mm long if straightened. DNA does not exist as a single strand, but instead as a pair of strands that are held together; these two long strands coil in the shape of a double helix. The nucleotide contains both a segment of the backbone of a nucleobase. A nucleobase linked to a sugar is called a nucleoside, a base linked to a sugar and to one or more phosphate groups is called a nucleotide.
A biopolymer comprising multiple linked nucleotides is called a polynucleotide. The backbone of the DNA strand is made from alternating sugar residues; the sugar in DNA is 2-deoxyribose, a pentose sugar. The sugars are joined together by phosphate groups that form phosphodiester bonds between the third and fifth carbon atoms of adjacent sugar rings; these are known as the 3′-end, 5′-end carbons, the prime symbol being used to distinguish these carbon atoms from those of the base to which the deoxyribose forms a glycosidic bond. When imagining DNA, each phosphoryl is considered to "belong" to the nucleotide whose 5′ carbon forms a bond therewith. Any DNA strand therefore has one end at which there is a phosphoryl attached to the 5′ carbon of a ribose and another end a
The Faroe Islands, or the Faeroe Islands—a North Atlantic archipelago located 200 miles north-northwest of the United Kingdom and about halfway between Norway and Iceland—are an autonomous country of the Kingdom of Denmark. Total area is about 1,400 square kilometres with a population of 50,322 in October 2017; the terrain is rugged. Temperatures average above freezing throughout the year because of the Gulf Stream. Between 1035 and 1814, the Faroes were part of the Hereditary Kingdom of Norway. In 1814, the Treaty of Kiel granted Denmark control over the islands, along with two other Norwegian island possessions: Greenland and Iceland; the Faroe Islands have been a self-governing country within the Kingdom of Denmark since 1948. The Faroese have control of most of their domestic affairs; those that are the responsibility of Denmark include military defence and the justice department and foreign affairs. However, as they are not part of the same customs area as Denmark, the Faroe Islands have an independent trade policy and can establish trade agreements with other states.
The islands have representation in the Nordic Council as members of the Danish delegation. The Faroe Islands have their own national teams competing in certain sports. In Faroese, the name appears as Føroyar. Oyar represents the plural of oy, older Faroese for "island". Due to sound changes, the modern Faroese word for island is oyggj; the first element, før, may reflect an Old Norse word fær, although this analysis is sometimes disputed because Faroese now uses the word seyður to mean "sheep". Another possibility is that the Irish monks, who settled the island around 625, had given the islands a name related to the Gaelic word fearrann, meaning "land" or "estate"; this name could have been passed on to the Norwegian settlers, who added oyar. The name thus translates as either "Islands of Sheep" or "Islands of Fearrann". In Danish, the name Færøerne contains the same elements, though øerne is the definite plural of ø. In English, it may be seen as redundant to say the Faroe Islands, since the oe comes from an element meaning "island".
Most notably in the BBC Shipping Forecast, where the waters around the islands are called Faeroes. The name is sometimes spelled "Faeroe". Archaeological evidence shows settlers living on the Faroe Islands in two successive periods before the Norse arrived, the first between 300 and 600 AD and the second between 600 and 800 AD. Scientists from the University of Aberdeen have found early cereal pollen from domesticated plants, which further suggests people may have lived on the islands before the Vikings arrived. Archaeologist Mike Church noted, he suggested that the people living there might have been from Ireland, Scotland, or Scandinavia with groups from all three areas settling there. A Latin account of a voyage made by Brendan, an Irish monastic saint who lived around 484–578, includes a description of insulae resembling the Faroe Islands; this association, however, is far from conclusive in its description. Dicuil, an Irish monk of the early 9th century, wrote a more definite account. In his geographical work De mensura orbis terrae he claimed he had reliable information of heremitae ex nostra Scotia who had lived on the northerly islands of Britain for a hundred years until the arrival of Norse pirates.
Norsemen settled the islands c. 800, bringing Old West Norse, which evolved into the modern Faroese language. According to Icelandic sagas such as Færeyjar Saga, one of the best known men in the island was Tróndur í Gøtu, a descendant of Scandinavian chiefs who had settled in Dublin, Ireland. Tróndur led the battle against the Norwegian monarchy and the Norwegian church; the Norse and Norse–Gael settlers did not come directly from Scandinavia, but rather from Norse communities surrounding the Irish Sea, Northern Isles and Outer Hebrides of Scotland, including the Shetland and Orkney islands. A traditional name for the islands in Irish, Na Scigirí refers to the Skeggjar "Beards", a nickname given to island dwellers. According to the Færeyinga saga, more emigrants left Norway who did not approve of the monarchy of Harald Fairhair; these people settled the Faroes around the end of the 9th century. Early in the 11th century, Sigmundur Brestisson – whose clan had flourished in the southern islands before invaders from the northern islands exterminated it – escaped to Norway.
He was sent back to take possession of the islands for Olaf Tryggvason, King of Norway from 995 to 1000. Sigmundur introduced Christianity, forcing Tróndur í Gøtu to convert or face beheading and, though Sigmundur was subsequently murdered, Norwegian taxation was upheld. Norwegian control of the Faroes continued until 1814, when the Kingdom of Norway entered the Kalmar Union with Denmark, it resulted in Danish control of the islands; the Reformation with Protestant Evangelical Lutheranism and Reformed reached the Faroes in 1538. When the union between Denmark and Norway dissolved as a result of the Treaty of Kiel in 1814, Denmark retained possession of the Faroe Islands. Following the turmoil caused by the Napoleonic Wars in 1816, the Faroe Islands became a county in the Danish Kingdom; as part of Mercantilism, Denmark maintained a monopoly over trade with the Faroe Islands and forbade their inhabitants trading
International Standard Serial Number
An International Standard Serial Number is an eight-digit serial number used to uniquely identify a serial publication, such as a magazine. The ISSN is helpful in distinguishing between serials with the same title. ISSN are used in ordering, interlibrary loans, other practices in connection with serial literature; the ISSN system was first drafted as an International Organization for Standardization international standard in 1971 and published as ISO 3297 in 1975. ISO subcommittee TC 46/SC 9 is responsible for maintaining the standard; when a serial with the same content is published in more than one media type, a different ISSN is assigned to each media type. For example, many serials are published both in electronic media; the ISSN system refers to these types as electronic ISSN, respectively. Conversely, as defined in ISO 3297:2007, every serial in the ISSN system is assigned a linking ISSN the same as the ISSN assigned to the serial in its first published medium, which links together all ISSNs assigned to the serial in every medium.
The format of the ISSN is an eight digit code, divided by a hyphen into two four-digit numbers. As an integer number, it can be represented by the first seven digits; the last code digit, which may be 0-9 or an X, is a check digit. Formally, the general form of the ISSN code can be expressed as follows: NNNN-NNNC where N is in the set, a digit character, C is in; the ISSN of the journal Hearing Research, for example, is 0378-5955, where the final 5 is the check digit, C=5. To calculate the check digit, the following algorithm may be used: Calculate the sum of the first seven digits of the ISSN multiplied by its position in the number, counting from the right—that is, 8, 7, 6, 5, 4, 3, 2, respectively: 0 ⋅ 8 + 3 ⋅ 7 + 7 ⋅ 6 + 8 ⋅ 5 + 5 ⋅ 4 + 9 ⋅ 3 + 5 ⋅ 2 = 0 + 21 + 42 + 40 + 20 + 27 + 10 = 160 The modulus 11 of this sum is calculated. For calculations, an upper case X in the check digit position indicates a check digit of 10. To confirm the check digit, calculate the sum of all eight digits of the ISSN multiplied by its position in the number, counting from the right.
The modulus 11 of the sum must be 0. There is an online ISSN checker. ISSN codes are assigned by a network of ISSN National Centres located at national libraries and coordinated by the ISSN International Centre based in Paris; the International Centre is an intergovernmental organization created in 1974 through an agreement between UNESCO and the French government. The International Centre maintains a database of all ISSNs assigned worldwide, the ISDS Register otherwise known as the ISSN Register. At the end of 2016, the ISSN Register contained records for 1,943,572 items. ISSN and ISBN codes are similar in concept. An ISBN might be assigned for particular issues of a serial, in addition to the ISSN code for the serial as a whole. An ISSN, unlike the ISBN code, is an anonymous identifier associated with a serial title, containing no information as to the publisher or its location. For this reason a new ISSN is assigned to a serial each time it undergoes a major title change. Since the ISSN applies to an entire serial a new identifier, the Serial Item and Contribution Identifier, was built on top of it to allow references to specific volumes, articles, or other identifiable components.
Separate ISSNs are needed for serials in different media. Thus, the print and electronic media versions of a serial need separate ISSNs. A CD-ROM version and a web version of a serial require different ISSNs since two different media are involved. However, the same ISSN can be used for different file formats of the same online serial; this "media-oriented identification" of serials made sense in the 1970s. In the 1990s and onward, with personal computers, better screens, the Web, it makes sense to consider only content, independent of media; this "content-oriented identification" of serials was a repressed demand during a decade, but no ISSN update or initiative occurred. A natural extension for ISSN, the unique-identification of the articles in the serials, was the main demand application. An alternative serials' contents model arrived with the indecs Content Model and its application, the digital object identifier, as ISSN-independent initiative, consolidated in the 2000s. Only in 2007, ISSN-L was defined in the