1.
Chemical reaction
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A chemical reaction is a process that leads to the transformation of one set of chemical substances to another. Nuclear chemistry is a sub-discipline of chemistry that involves the reactions of unstable. The substance initially involved in a reaction are called reactants or reagents. Chemical reactions are characterized by a chemical change, and they yield one or more products. Reactions often consist of a sequence of individual sub-steps, the elementary reactions. Chemical reactions are described with chemical equations, which present the starting materials, end products. Chemical reactions happen at a characteristic reaction rate at a given temperature, typically, reaction rates increase with increasing temperature because there is more thermal energy available to reach the activation energy necessary for breaking bonds between atoms. Reactions may proceed in the forward or reverse direction until they go to completion or reach equilibrium, Reactions that proceed in the forward direction to approach equilibrium are often described as spontaneous, requiring no input of free energy to go forward. Non-spontaneous reactions require input of energy to go forward. Different chemical reactions are used in combinations during chemical synthesis in order to obtain a desired product, in biochemistry, a consecutive series of chemical reactions form metabolic pathways. These reactions are catalyzed by protein enzymes. Chemical reactions such as combustion in fire, fermentation and the reduction of ores to metals were known since antiquity, in the Middle Ages, chemical transformations were studied by Alchemists. They attempted, in particular, to lead into gold, for which purpose they used reactions of lead. The process involved heating of sulfate and nitrate minerals such as sulfate, alum. In the 17th century, Johann Rudolph Glauber produced hydrochloric acid and sodium sulfate by reacting sulfuric acid, further optimization of sulfuric acid technology resulted in the contact process in the 1880s, and the Haber process was developed in 1909–1910 for ammonia synthesis. From the 16th century, researchers including Jan Baptist van Helmont, Robert Boyle, the phlogiston theory was proposed in 1667 by Johann Joachim Becher. It postulated the existence of an element called phlogiston, which was contained within combustible bodies. This proved to be false in 1785 by Antoine Lavoisier who found the explanation of the combustion as reaction with oxygen from the air
2.
Catalysis
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Catalysis is the increase in the rate of a chemical reaction due to the participation of an additional substance called a catalyst. In most cases, reactions occur faster with a catalyst because they require less activation energy, furthermore, since they are not consumed in the catalyzed reaction, catalysts can continue to act repeatedly. Often only tiny amounts are required in principle, in the presence of a catalyst, less free energy is required to reach the transition state, but the total free energy from reactants to products does not change. A catalyst may participate in multiple chemical transformations, the effect of a catalyst may vary due to the presence of other substances known as inhibitors or poisons or promoters. Catalyzed reactions have an activation energy than the corresponding uncatalyzed reaction, resulting in a higher reaction rate at the same temperature. However, the mechanics of catalysis is complex. Usually, the catalyst participates in this slowest step, and rates are limited by amount of catalyst, in heterogeneous catalysis, the diffusion of reagents to the surface and diffusion of products from the surface can be rate determining. A nanomaterial-based catalyst is an example of a heterogeneous catalyst, analogous events associated with substrate binding and product dissociation apply to homogeneous catalysts. Although catalysts are not consumed by the reaction itself, they may be inhibited, deactivated, in heterogeneous catalysis, typical secondary processes include coking where the catalyst becomes covered by polymeric side products. Additionally, heterogeneous catalysts can dissolve into the solution in a system or sublimate in a solid–gas system. The production of most industrially important chemicals involves catalysis, similarly, most biochemically significant processes are catalysed. Research into catalysis is a field in applied science and involves many areas of chemistry, notably organometallic chemistry. Catalysis is relevant to aspects of environmental science, e. g. the catalytic converter in automobiles. Many transition metals and transition metal complexes are used in catalysis as well, Catalysts called enzymes are important in biology. A catalyst works by providing a reaction pathway to the reaction product. The rate of the reaction is increased as this route has a lower activation energy than the reaction route not mediated by the catalyst. The disproportionation of hydrogen peroxide creates water and oxygen, as shown below,2 H2O2 →2 H2O + O2 This reaction is preferable in the sense that the reaction products are more stable than the starting material, though the uncatalysed reaction is slow. In fact, the decomposition of hydrogen peroxide is so slow that hydrogen peroxide solutions are commercially available and this reaction is strongly affected by catalysts such as manganese dioxide, or the enzyme peroxidase in organisms
3.
Transferase
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A transferase is any one of a class of enzymes that enact the transfer of specific functional groups from one molecule to another. They are involved in hundreds of different biochemical pathways throughout biology, transferases are involved in myriad reactions in the cell. Transferases are also utilized during translation, in this case, an amino acid chain is the functional group transferred by a peptidyl transferase. Group would be the group transferred as a result of transferase activity. The donor is often a coenzyme, some of the most important discoveries relating to transferases occurred as early as the 1930s. Earliest discoveries of transferase activity occurred in other classifications of enzymes, including Beta-galactosidase, protease, prior to the realization that individual enzymes were capable of such a task, it was believed that two or more enzymes enacted functional group transfers. This observance was later verified by the discovery of its reaction mechanism by Braunstein and their analysis showed that this reversible reaction could be applied to other tissues. This assertion was validated by Rudolf Schoenheimers work with radioisotopes as tracers in 1937 and this in turn would pave the way for the possibility that similar transfers were a primary means of producing most amino acids via amino transfer. Another such example of early research and later reclassification involved the discovery of uridyl transferase. In 1953, the enzyme UDP-glucose pyrophosphorylase was shown to be a transferase, when it was found that it could reversibly produce UTP and G1P from UDP-glucose, another example of historical significance relating to transferase is the discovery of the mechanism of catecholamine breakdown by catechol-O-methyltransferase. This discovery was a part of the reason for Julius Axelrod’s 1970 Nobel Prize in Physiology or Medicine. Classification of transferases continues to this day, with new ones being discovered frequently, an example of this is Pipe, a sulfotransferase involved in the dorsal-ventral patterning of Drosophilia. Initially, the mechanism of Pipe was unknown, due to a lack of information on its substrate. Research into Pipes catalytic activity eliminated the likelihood of it being a heparan sulfate glycosaminoglycan, further research has shown that Pipe targets the ovarian structures for sulfation. Pipe is currently classified as a Drosophilia heparan sulfate 2-O-sulfotransferase, systematic names of transferases are constructed in the form of donor, acceptor grouptransferase. For example, a DNA methyltransferase is a transferase that catalyzes the transfer of a group to a DNA acceptor. In practice, many molecules are not referred to using this terminology due to more prevalent common names, in the EC system of classification, the accepted name for RNA Polymerase is DNA-directed RNA polymerase. Described primarily based on the type of biochemical group transferred, transferases can be divided into ten categories and these categories comprise over 450 different unique enzymes
4.
Enzyme
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Enzymes /ˈɛnzaɪmz/ are macromolecular biological catalysts. Enzymes accelerate, or catalyze, chemical reactions, the molecules at the beginning of the process upon which enzymes may act are called substrates and the enzyme converts these into different molecules, called products. Almost all metabolic processes in the cell need enzymes in order to occur at rates fast enough to sustain life, the set of enzymes made in a cell determines which metabolic pathways occur in that cell. The study of enzymes is called enzymology, enzymes are known to catalyze more than 5,000 biochemical reaction types. Most enzymes are proteins, although a few are catalytic RNA molecules, enzymes specificity comes from their unique three-dimensional structures. Like all catalysts, enzymes increase the rate of a reaction by lowering its activation energy, some enzymes can make their conversion of substrate to product occur many millions of times faster. An extreme example is orotidine 5-phosphate decarboxylase, which allows a reaction that would take millions of years to occur in milliseconds. Chemically, enzymes are like any catalyst and are not consumed in chemical reactions, enzymes differ from most other catalysts by being much more specific. Enzyme activity can be affected by other molecules, inhibitors are molecules that decrease enzyme activity, many drugs and poisons are enzyme inhibitors. An enzymes activity decreases markedly outside its optimal temperature and pH, some enzymes are used commercially, for example, in the synthesis of antibiotics. French chemist Anselme Payen was the first to discover an enzyme, diastase and he wrote that alcoholic fermentation is an act correlated with the life and organization of the yeast cells, not with the death or putrefaction of the cells. In 1877, German physiologist Wilhelm Kühne first used the term enzyme, the word enzyme was used later to refer to nonliving substances such as pepsin, and the word ferment was used to refer to chemical activity produced by living organisms. Eduard Buchner submitted his first paper on the study of yeast extracts in 1897, in a series of experiments at the University of Berlin, he found that sugar was fermented by yeast extracts even when there were no living yeast cells in the mixture. He named the enzyme that brought about the fermentation of sucrose zymase, in 1907, he received the Nobel Prize in Chemistry for his discovery of cell-free fermentation. Following Buchners example, enzymes are usually named according to the reaction they carry out, the biochemical identity of enzymes was still unknown in the early 1900s. Sumner showed that the enzyme urease was a protein and crystallized it. These three scientists were awarded the 1946 Nobel Prize in Chemistry, the discovery that enzymes could be crystallized eventually allowed their structures to be solved by x-ray crystallography. This high-resolution structure of lysozyme marked the beginning of the field of structural biology, an enzymes name is often derived from its substrate or the chemical reaction it catalyzes, with the word ending in -ase
5.
Glycogen debranching enzyme
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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 this constitutes a major source of energy reserves in most organisms. Glycogen breakdown is highly regulated in the body, especially in the liver, by various hormones including insulin and glucagon, 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 an enzyme in mammals, yeast, and some bacteria. Proteins that catalyze both functions are referred to as glycogen debranching enzymes, when glucosyltransferase and glucosidase are catalyzed by distinct enzymes, glycogen debranching enzyme usually 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, 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. The mechanism by which the glucosidase cleaves the α -1, 6-linkage is not fully known because the amino acids in the 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, and retention of configuration in glucose. This is a method through which to cleave bonds, with an acid below the site of hydrolysis to lend a proton. These acids and bases are amino acid 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 and this enzyme has a molecular mass of 73.6 kDa, and is coded for by the gene glgX. Activity of the two enzymes is not always necessarily coupled, in E. coli glgX selectively catalyzes the cleavage of 4-subunit branches, without the action of glucanotransferase. The product of 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
6.
Glucuronosyltransferase
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Uridine 5-diphospho-glucuronosyltransferase is a cytosolic glycosyltransferase that catalyzes the transfer of the glucuronic acid component of UDP-glucuronic acid to a small hydrophobic molecule. Alternative names, glucuronyltransferase UDP-glucuronyl transferase UDP-GT Glucuronosyltransferases are responsible for the process of glucuronidation, arguably the most important of the Phase II enzymes, UGTs have been the subject of increasing scientific inquiry since the mid-to-late 1990s. It is also the pathway for foreign chemical removal for most drugs, dietary substances, toxins. UGT is present in humans, other animals, plants, famously, UGT enzymes are not present in the genus Felis, and this accounts for a number of unusual toxicities in the cat family. The resulting glucuronide is more polar and more easily excreted than the substrate molecule, the product solubility in blood is increased allowing it to be eliminated from the body by the kidneys. A deficiency in the specific form of glucuronosyltransferase is thought to be the cause of Gilberts syndrome. It is also associated with Crigler-Najjar syndrome, a serious disorder where the enzymes activity is either completely absent or less than 10% of normal. Infants may have a deficiency in UDP-glucuronyl transferase, and are unable to hepatically metabolize the antibiotic drug chloramphenicol which requires glucuronidation. This leads to a known as gray baby syndrome
7.
Glycogen phosphorylase
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Glycogen phosphorylase is one of the phosphorylase enzymes. Glycogen phosphorylase catalyzes the rate-limiting step in glycogenolysis in animals by releasing glucose-1-phosphate from the terminal alpha-1, Glycogen phosphorylase is also studied as a model protein regulated by both reversible phosphorylation and allosteric effects. Glycogen phosphorylase breaks up glycogen into glucose subunits, n + Pi ⇌ n-1 + α-D-glucose-1-phosphate, Glycogen is left with one fewer glucose molecule, and the free glucose molecule is in the form of glucose-1-phosphate. In order to be used for metabolism, it must be converted to glucose-6-phosphate by the enzyme phosphoglucomutase, Glycogen phosphorylase can act only on linear chains of glycogen. Its work will come to a halt four residues away from α1-6 branch. In these situations, an enzyme is necessary, which will straighten out the chain in that area. After all this is done, glycogen phosphorylase can continue and this crevice connects the glycogen storage site to the active, catalytic site. Glycogen phosphorylase has a pyridoxal phosphate at each catalytic site, pyridoxal phosphate links with basic residues and covalently forms a Schiff base. There is also a proposed mechanism involving a positively charged oxygen in a half-chair conformation. The glycogen phosphorylase monomer is a protein, composed of 842 amino acids with a mass of 97.434 kDa in muscle cells. While the enzyme can exist as a monomer or tetramer. In mammals, the major isozymes of glycogen phosphorylase are found in muscle, liver, the brain type is predominant in adult brain and embryonic tissues, whereas the liver and muscle types are predominant in adult liver and skeletal muscle, respectively. The glycogen phosphorylase dimer has many regions of biological significance, including sites, glycogen binding sites, allosteric sites. First, the sites are relatively buried, 15Å from the surface of the protein. Perhaps the most important regulatory site is Ser14, the site of reversible phosphorylation very close to the subunit interface. The structural change associated with phosphorylation, and with the conversion of phosphorylase b to phosphorylase a, is the arrangement of the originally disordered residues 10 to 22 into α helices. This change increases phosphorylase activity up to 25% even in the absence of AMP, the allosteric site of AMP binding on muscle isoforms of glycogen phosphorylase are close to the subunit interface just like Ser14. AMP binding rotates the tower helices of the two subunits 50˚ relative to one another through greater organization and intersubunit interactions, the final, perhaps most curious site on the glycogen phosphorylase protein is the so-called glycogen storage site
8.
Protein Data Bank
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The Protein Data Bank is a crystallographic database for the three-dimensional structural data of large biological molecules, such as proteins and nucleic acids. The PDB is overseen by a called the Worldwide Protein Data Bank. The PDB is a key resource in areas of structural biology, most major scientific journals, and some funding agencies, now require scientists to submit their structure data to the PDB. Many other databases use protein structures deposited in the PDB, for example, SCOP and CATH classify protein structures, while PDBsum provides a graphic overview of PDB entries using information from other sources, such as Gene ontology. By 1971, one of Meyers programs, SEARCH, enabled researchers to access information from the database to study protein structures offline. SEARCH was instrumental in enabling networking, thus marking the beginning of the PDB. Upon Hamiltons death in 1973, Tom Koeztle took over direction of the PDB for the subsequent 20 years, in January 1994, Joel Sussman of Israels Weizmann Institute of Science was appointed head of the PDB. In October 1998, the PDB was transferred to the Research Collaboratory for Structural Bioinformatics, the new director was Helen M. Berman of Rutgers University. In 2003, with the formation of the wwPDB, the PDB became an international organization, the founding members are PDBe, RCSB, and PDBj. Each of the four members of wwPDB can act as deposition, data processing, the data processing refers to the fact that wwPDB staff review and annotate each submitted entry. The data are automatically checked for plausibility. The PDB database is updated weekly, likewise, the PDB holdings list is also updated weekly. As of 14 March 2017, the breakdown of current holdings is as follows,103,514 structures in the PDB have a structure factor file,9,057 structures have an NMR restraint file. 2,826 structures in the PDB have a chemical shifts file, therefore, the final conformation of the protein is obtained, in the latter case, by solving a distance geometry problem. A few proteins are determined by cryo-electron microscopy, the significance of the structure factor files, mentioned above, is that, for PDB structures determined by X-ray diffraction that have a structure file, the electron density map may be viewed. The data of such structures is stored on the electron density server, however, since 2007, the rate of accumulation of new protein structures appears to have plateaued. The file format used by the PDB was called the PDB file format. This original format was restricted by the width of computer punch cards to 80 characters per line, around 1996, the macromolecular Crystallographic Information file format, mmCIF, which is an extension of the CIF format started to be phased in
9.
Glycosyltransferase
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Glycosyltransferases are enzymes that establish natural glycosidic linkages. The result of transfer can be a carbohydrate, glycoside, oligosaccharide. Some glycosyltransferases catalyse transfer to inorganic phosphate or water, glycosyl transfer can also occur to protein residues, usually to tyrosine, serine, or threonine to give O-linked glycoproteins, or to asparagine to give N-linked glycoproteins. Mannosyl groups may be transferred to tryptophan to generate C-mannosyl tryptophan, transferases may also use lipids as an acceptor, forming glycolipids, and even use lipid-linked sugar phosphate donors, such as dolichol phosphates. Glycosyltransferases that utilize non-nucleotide donors such as dolichol or polyprenol pyrophosphate are non-Leloir glycosyltransferases, the phosphate of these donor molecules are usually coordinated by divalent cations such as manganese, however metal independent enzymes exist. Glycosyltransferases can be segregated into “retaining” or“ inverting” enzymes according to whether the stereochemistry of the donor’s anomeric bond is retained or inverted during the transfer, the inverting mechanism is straightforward, requiring a single nucleophilic attack from the accepting atom to invert stereochemistry. The retaining mechanism has been a matter of debate, but there exists strong evidence against a double displacement mechanism or a dissociative mechanism, sequence-based classification methods have proven to be a powerful way of generating hypotheses for protein function based on sequence alignment to related proteins. The carbohydrate-active enzyme database presents a classification of glycosyltransferases into over 90 families. The same three-dimensional fold is expected to occur within each of the families, in contrast to the diversity of 3D structures observed for glycoside hydrolases, glycosyltransferase have a much smaller range of structures. Many inhibitors of glycosyltransferases are known, some glycosyltransferase inhibitors are of use as drugs or antibiotics. Moenimycin is used in animal feed as a growth promoter, caspofungin has been developed from the echinocandins and is in use as an antifungal agent. Ethambutol is an inhibitor of mycobacterial arabinotransferases and is used for the treatment of tuberculosis, lufenuron is an inhibitor of insect chitin synthases and is used to control fleas in animals. The ABO blood group system is determined by type of glucosyltransferases are expressed in the body. The ABO gene locus expressing the glucosyltransferases has three main forms, A, B, and O. The A allele encodes 1-3-N-acetylgalactosaminyltransferase that bonds α-N-acetylgalactosamine to D-galactose end of H antigen, the B allele encodes 1-3-galactosyltransferase that joins α-D-galactose bonded to D-galactose end of H antigen, creating the B antigen. In case of O allele the exon 6 contains a deletion that results in a loss of enzymatic activity, the O allele differs slightly from the A allele by deletion of a single nucleotide - Guanine at position 261. The deletion causes a frameshift and results in translation of an almost entirely different protein that lacks enzymatic activity and this results in H antigen remaining unchanged in case of O groups. The combination of glucosyltransferases by both present in each person determines whether there is an AB, A, B or O blood type
10.
Myophosphorylase
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Myophosphorylase is the muscle isoform of the enzyme glycogen phosphorylase. This enzyme helps break down glycogen into glucose-1-phosphate, so that it can be utilized within the muscle cell, a deficiency is associated with Glycogen storage disease type V, also known as McArdles Syndrome. A case study suggested that a deficiency in myophosphorylase may be linked with cognitive impairment, besides muscle, this isoform is present in astrocytes, where it plays a key role in neural energy metabolism. A 55-year-old woman with McArdle disease has expressed cognitive impairment with bilateral dysfunction of prefrontal and frontal cortex, further studies are needed to assess the validity of this claim. Myophosphorylase at the US National Library of Medicine Medical Subject Headings
