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.
Aminoacyl tRNA synthetase
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An aminoacyl tRNA synthetase is an enzyme that attaches the appropriate amino acid onto its tRNA. It does so by catalyzing the esterification of a specific amino acid or its precursor to one of all its compatible cognate tRNAs to form an aminoacyl-tRNA. In humans, the 21 different types of aa-tRNA are made by the 21 different aminoacyl-tRNA synthetases and this is sometimes called charging or loading the tRNA with the amino acid. Once the tRNA is charged, a ribosome can transfer the amino acid from the tRNA onto a growing peptide, aminoacyl tRNA therefore plays an important role in DNA translation, the expression of genes to create proteins. The synthetase first binds ATP and the amino acid to form an aminoacyl-adenylate. The adenylate-aaRS complex then binds the appropriate tRNA molecules D arm, if the incorrect tRNA is added, the aminoacyl-tRNA bond is hydrolyzed. This can happen when two amino acids have different properties even if they have similar shapes—as is the case with Valine and Threonine, there are two classes of aminoacyl tRNA synthetase, Class I has two highly conserved sequence motifs. It aminoacylates at the 2-OH of a terminal adenosine nucleotide on tRNA, Class II has three highly conserved sequence motifs. It aminoacylates at the 3-OH of a terminal adenosine on tRNA, although phenylalanine-tRNA synthetase is class II, it aminoacylates at the 2-OH. The amino acids are attached to the group of the adenosine via the carboxyl group. Regardless of where the aminoacyl is initially attached to the nucleotide, both classes of aminoacyl-tRNA synthetases are multidomain proteins. In a typical scenario, an aaRS consists of a catalytic domain, in addition, some aaRSs have additional RNA binding domains and editing domains that cleave incorrectly paired aminoacyl-tRNA molecules. The catalytic domains of all the aaRSs of a class are found to be homologous to one another, whereas class I. The class I aaRSs have the ubiquitous Rossmann fold and have the parallel beta-strands architecture, the alpha helical anticodon binding domain of Arginyl, Glycyl and Cysteinyl-tRNA synthetases is known as the DALR domain after characteristic conserved amino acids. Most of the aaRSs of a given specificity are evolutionarily closer to one another than to aaRSs of another specificity, however, AsnRS and GlnRS group within AspRS and GluRS, respectively. Most of the aaRSs of a given specificity also belong to a single class, however, there are two distinct versions of the LysRS - one belonging to the class I family and the other belonging to the class II family. In addition, the phylogenies of aaRSs are often not consistent with accepted organismal phylogenies. That is, they violate the so-called canonical phylogenetic pattern shown by most other enzymes for the three domains of life - Archaea, Bacteria, and Eukarya, furthermore, the phylogenies inferred for aaRSs of different amino acids often do not agree with one another
3.
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
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.
Journal of the American Chemical Society
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The Journal of the American Chemical Society is a weekly peer-reviewed scientific journal that was established in 1879 by the American Chemical Society. The journal has absorbed two other publications in its history, the Journal of Analytical and Applied Chemistry and the American Chemical Journal and it publishes original research papers in all fields of chemistry. Since 2002, the journal is edited by Peter J. Stang, in 2014, the journal moved to a hybrid open access publishing model. The Journal of the American Chemical Society is abstracted and indexed in Chemical Abstracts Service, Scopus, EBSCOhost, Thomson-Gale, ProQuest, PubMed, Web of Science, and SwetsWise. According to the Journal Citation Reports, it had a factor of 12.113 for 2014
6.
Adenosine triphosphate
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Adenosine triphosphate is a nucleotide, also called a nucleoside triphosphate, is a small molecule used in cells as a coenzyme. It is often referred to as the unit of currency of intracellular energy transfer. ATP transports chemical energy within cells for metabolism, most cellular functions need energy in order to be carried out, synthesis of proteins, synthesis of membranes, movement of the cell, cellular division, transport of various solutes etc. The ATP is the molecule that carries energy to the place where the energy is needed, when ATP breaks into ADP and Pi, the breakdown of the last covalent link of phosphate liberates energy that is used in reactions where it is needed. Substrate-level phosphorylation, oxidative phosphorylation in cellular respiration, and photophosphorylation in photosynthesis are three mechanisms of ATP biosynthesis. Metabolic processes that use ATP as an energy source convert it back into its precursors, ATP is therefore continuously recycled in organisms, the human body, which on average contains only 250 grams of ATP, turns over its own body weight equivalent in ATP each day. ATP is used as a substrate in signal transduction pathways by kinases that phosphorylate proteins and it is also used by adenylate cyclase, which uses ATP to produce the second messenger molecule cyclic AMP. The ratio between ATP and AMP is used as a way for a cell to sense how much energy is available and control the metabolic pathways that produce and consume ATP. Apart from its roles in signaling and energy metabolism, ATP is also incorporated into nucleic acids by polymerases in the process of transcription, ATP is the neurotransmitter believed to signal the sense of taste. The structure of this consists of a purine base attached by the 9′ nitrogen atom to the 1′ carbon atom of a pentose sugar. Three phosphate groups are attached at the 5′ carbon atom of the pentose sugar and it is the addition and removal of these phosphate groups that inter-convert ATP, ADP and AMP. When ATP is used in DNA synthesis, the sugar is first converted to deoxyribose by ribonucleotide reductase. ATP was discovered in 1929 by Karl Lohmann, and independently by Cyrus Fiske and Yellapragada Subbarow of Harvard Medical School and it was proposed to be the intermediary molecule between energy-yielding and energy-requiring reactions in cells by Fritz Albert Lipmann in 1941. It was first artificially synthesized by Alexander Todd in 1948, ATP consists of adenosine – composed of an adenine ring and a ribose sugar – and three phosphate groups. The phosphoryl groups, starting with the group closest to the ribose, are referred to as the alpha, beta, consequently, it is closely related to the adenosine nucleotide, a monomer of RNA. ATP is highly soluble in water and is stable in solutions between pH6.8 and 7.4, but is rapidly hydrolysed at extreme pH. Consequently, ATP is best stored as an anhydrous salt, ATP is an unstable molecule in unbuffered water, in which it hydrolyses to ADP and phosphate. This is because the strength of the bonds between the groups in ATP is less than the strength of the hydrogen bonds, between its products, and water
7.
Clavulanic acid
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Clavulanic acid is a β-lactam drug that functions as a mechanism-based β-Lactamase inhibitor. In its most common form, the potassium salt potassium clavulanate is combined with, clavulanic acid is an example of a clavam. Clavulanic acid was patented in 1974, for the treatment of pyelonephritis during pregnancy, and for the treatment of pyelonephritis caused by gram-positive organisms, amoxicillin or amoxicillin-clavulanate potassium is preferred. The name is derived from strains of Streptomyces clavuligerus, which produces clavulanic acid, clavulanic acid is biosynthetically generated from the amino acid arginine and the sugar glyceraldehyde 3-phosphate. With the β-lactam like structure, clavulanic acid looks structurally similar to penicillin, clavulanic acid is biosynthesized by the bacterium Streptomyces clavuligerus, using glyceraldehyde-3-phosphate and L-arginine as the starting materials of the pathway. Although all of the intermediates of the pathway are known, the mechanism of each enzymatic reaction is not fully understood. The biosynthesis mainly involves 3 enzymes, clavaminate synthase, β-lactam synthetase, clavaminate synthase is a non-heme iron α-keto-glutarate dependent oxygenase that is encoded by orf5 of the clavulanic acid gene cluster. The specific mechanism of how this works is not fully understood. All 3 steps occur in the region of the catalytic iron center, yet do not occur in-sequence. β-lactam synthetase is a 54.5 kDa protein that is encoded by orf3 of the clavulanic acid gene cluster, the exact mechanism on how this enzyme works to synthesize the β-lactam is not proven, but is believed to occur in coordination with a CEA synthase and ATP. CEA synthase is a 60.9 kDA protein and is the first gene found in the clavulanic acid gene cluster. Clavulanic acid was discovered around 1974/75 by British scientists working at the drug company Beecham, after several attempts, Beecham finally filed for US patent protection for the drug in 1981, and U. S. Patents 4,525,352,4,529,720, clavulanic acid has negligible intrinsic antimicrobial activity, despite sharing the β-lactam ring that is characteristic of β-lactam antibiotics. However, the similarity in chemical structure allows the molecule to interact with the enzyme β-lactamase secreted by bacteria to confer resistance to β-lactam antibiotics. Clavulanic acid is an inhibitor, covalently bonding to a serine residue in the active site of the β-lactamase. This inhibition restores the antimicrobial activity of β-lactam antibiotics against lactamase-secreting resistant bacteria, despite this, some bacterial strains that are resistant even to such combinations have emerged. The use of clavulanic acid with penicillins has been associated with an incidence of cholestatic jaundice. The associated jaundice is usually self-limiting and very rarely fatal
8.
Succinyl coenzyme A synthetase
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Succinyl coenzyme A synthetase is an enzyme that catalyzes the reversible reaction of succinyl-CoA to succinate. The enzyme facilitates the coupling of this reaction to the formation of a nucleoside triphosphate molecule from a phosphate molecule. It plays a key role as one of the involved in the citric acid cycle, a central pathway in cellular metabolism. As mentioned, the enzyme facilitates coupling of the conversion of succinyl CoA to succinate with the formation of NTP from NDP, the reaction has a biochemical standard state free energy change of -3.4 kJ/mol. The reaction takes place by a mechanism which is depicted in the image below. The first step involves displacement of CoA from succinyl CoA by an inorganic phosphate molecule to form succinyl phosphate. The enzyme then utilizes a histidine residue to remove the group from succinyl phosphate and generate succinate. Finally, the histidine transfers the phosphate group to a nucleoside diphosphate. Bacterial and mammalian SCSs are made up of α and β subunits, in E. coli two αβ heterodimers link together to form an α2β2 heterotetrameric structure. However, mammalian mitochondrial SCSs are active as αβ dimers and do not form a heterotetramer, the E. coli SCS heterotetramer has been crystallized and characterized in great detail. As can be seen in Image 2, the two α subunits reside on opposite sides of the structure and the two β subunits interact in the region of the protein. The two α subunits only interact with a single β unit, whereas the β units interact with a single α unit, a short amino acid chain links the two β subunits which gives rise to the tetrameric structure. The crystal structure of Succinyl-CoA synthetase alpha subunit was determined by Joyce et al. to a resolution of 2.10 A, crystal structures for the E. coli SCS provide evidence that the coenzyme A binds within each α-subunit in close proximity to a histidine residue. This histidine residue becomes phosphorylated during the forming step in the reaction mechanism. The exact binding location of succinate is not well-defined, the formation of the nucleoside triphosphate occurs in an ATP grasp domain, which is located near the N-terminus of the each β subunit. However, this domain is located about 35 Å away from the phosphorylated histidine residue. This leads researchers to believe that the enzyme must undergo a change in conformation to bring the histidine to the grasp domain. Johnson et al. describe two isoforms of succinyl-CoA synthetase in mammals, one that specifies synthesis of ADP, and one that synthesises GDP
9.
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
10.
Pyrophosphate
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In chemistry, a pyrophosphate is a phosphorus oxyanion. Compounds such as salts and esters are called pyrophosphates. The group is also called diphosphate or dipolyphosphate, although this should not be confused with phosphates, as a food additive, diphosphates are known as E450. A number of hydrogen pyrophosphates also exist, such as Na2H2P2O7, pyrophosphates were originally prepared by heating phosphates. They generally exhibit the highest solubilities among the phosphates, moreover, pyrophosphate is the first member of an entire series of polyphosphates. The term pyrophosphate is also the name of esters formed by the condensation of a phosphorylated biological compound with inorganic phosphate and this bond is also referred to as a high-energy phosphate bond. The synthesis of tetraethyl pyrophosphate was first described in 1854 by Philippe de Clermont at a meeting of the French Academy of Sciences, pyrophosphates are very important in biochemistry. The anion P2O74− is abbreviated PPi and is formed by the hydrolysis of ATP into AMP in cells, ATP → AMP + PPi For example, when a nucleotide is incorporated into a growing DNA or RNA strand by a polymerase, pyrophosphate is released. The pyrophosphate anion has the structure P2O74−, and is an anhydride of phosphate. This hydrolysis to inorganic phosphate effectively renders the cleavage of ATP to AMP and PPi irreversible, PPi occurs in synovial fluid, blood plasma, and urine at levels sufficient to block calcification and may be a natural inhibitor of hydroxyapatite formation in extracellular fluid. Cells may channel intracellular PPi into ECF, ANK is a nonenzymatic plasma-membrane PPi channel that supports extracellular PPi levels. Defective function of the membrane PPi channel ANK is associated with low extracellular PPi, ectonucleotide pyrophosphatase/phosphodiesterase may function to raise extracellular PPi. AMP + ATP →2 ADP2 ADP +2 Pi →2 ATP The plasma concentration of inorganic pyrophosphate has a range of 0. 58-3.78 µM. Various diphosphates are used as emulsifiers, stabilisers, acidity regulators, raising agents, sequestrants, schröder HC, Kurz L, Muller WE, Lorenz B. Pyrophosphates at the US National Library of Medicine Medical Subject Headings
. PMID 12409610.
