1.
Biochemistry
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Biochemistry, sometimes called biological chemistry, is the study of chemical processes within and relating to living organisms. By controlling information flow through biochemical signaling and the flow of energy through metabolism. Biochemistry is closely related to biology, the study of the molecular mechanisms by which genetic information encoded in DNA is able to result in the processes of life. Depending on the definition of the terms used, molecular biology can be thought of as a branch of biochemistry, or biochemistry as a tool with which to investigate. The chemistry of the cell depends on the reactions of smaller molecules. These can be inorganic, for water and metal ions, or organic, for example the amino acids. The mechanisms by which cells harness energy from their environment via chemical reactions are known as metabolism, the findings of biochemistry are applied primarily in medicine, nutrition, and agriculture. In medicine, biochemists investigate the causes and cures of diseases, in nutrition, they study how to maintain health and study the effects of nutritional deficiencies. In agriculture, biochemists investigate soil and fertilizers, and try to discover ways to improve crop cultivation, crop storage and pest control. However, biochemistry as a scientific discipline has its beginning sometime in the 19th century, or a little earlier. Gowland Hopkins on enzymes and the nature of biochemistry. The term biochemistry itself is derived from a combination of biology, the German chemist Carl Neuberg however is often cited to have coined the word in 1903, while some credited it to Franz Hofmeister. Then, in 1828, Friedrich Wöhler published a paper on the synthesis of urea and these techniques allowed for the discovery and detailed analysis of many molecules and metabolic pathways of the cell, such as glycolysis and the Krebs cycle. Another significant historic event in biochemistry is the discovery of the gene and this part of biochemistry is often called molecular biology. In the 1950s, James D. Watson, Francis Crick, Rosalind Franklin, in 1958, George Beadle and Edward Tatum received the Nobel Prize for work in fungi showing that one gene produces one enzyme. In 1988, Colin Pitchfork was the first person convicted of murder with DNA evidence, mello received the 2006 Nobel Prize for discovering the role of RNA interference, in the silencing of gene expression. Around two dozen of the 92 naturally occurring elements are essential to various kinds of biological life. Most rare elements on Earth are not needed by life, while a few common ones are not used, most organisms share element needs, but there are a few differences between plants and animals
2.
Enzyme inhibitor
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An enzyme inhibitor is a molecule that binds to an enzyme and decreases its activity. Since blocking an enzymes activity can kill a pathogen or correct a metabolic imbalance and they are also used in pesticides. The binding of an inhibitor can stop a substrate from entering the active site and/or hinder the enzyme from catalyzing its reaction. Inhibitor binding is reversible or irreversible. Irreversible inhibitors usually react with the enzyme and change it chemically and these inhibitors modify key amino acid residues needed for enzymatic activity. In contrast, reversible inhibitors bind non-covalently and different types of inhibition are produced depending on whether these inhibitors bind to the enzyme, many drug molecules are enzyme inhibitors, so their discovery and improvement is an active area of research in biochemistry and pharmacology. A medicinal enzyme inhibitor is often judged by its specificity and its potency, a high specificity and potency ensure that a drug will have few side effects and thus low toxicity. Enzyme inhibitors also occur naturally and are involved in the regulation of metabolism, for example, enzymes in a metabolic pathway can be inhibited by downstream products. This type of negative feedback slows the production line when products begin to build up and is an important way to maintain homeostasis in a cell, other cellular enzyme inhibitors are proteins that specifically bind to and inhibit an enzyme target. This can help control enzymes that may be damaging to a cell, a well-characterised example of this is the ribonuclease inhibitor, which binds to ribonucleases in one of the tightest known protein–protein interactions. Natural enzyme inhibitors can also be poisons and are used as defences against predators or as ways of killing prey, reversible inhibitors attach to enzymes with non-covalent interactions such as hydrogen bonds, hydrophobic interactions and ionic bonds. Multiple weak bonds between the inhibitor and the active site combine to produce strong and specific binding, in contrast to substrates and irreversible inhibitors, reversible inhibitors generally do not undergo chemical reactions when bound to the enzyme and can be easily removed by dilution or dialysis. There are four kinds of reversible enzyme inhibitors and they are classified according to the effect of varying the concentration of the enzymes substrate on the inhibitor. In competitive inhibition, the substrate and inhibitor cannot bind to the enzyme at the same time, as shown in the figure on the right. This usually results from the inhibitor having an affinity for the site of an enzyme where the substrate also binds. This type of inhibition can be overcome by high concentrations of substrate. However, the apparent Km will increase as it takes a higher concentration of the substrate to reach the Km point, competitive inhibitors are often similar in structure to the real substrate. In uncompetitive inhibition, the inhibitor binds only to the substrate-enzyme complex and this type of inhibition causes Vmax to decrease and Km to decrease
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.
Isomerase
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Isomerases are a general class of enzymes which convert a molecule from one isomer to another. Isomerases can either facilitate intramolecular rearrangements in which bonds are broken, the general form of such a reaction is as follows, A–B → B–A There is only one substrate yielding one product. This product has the molecular formula as the substrate but differs in bond connectivity or spatial arrangements. Isomerases catalyze reactions across many biological processes, such as in glycolysis, Isomerases catalyze changes within one molecule. They convert one isomer to another, meaning that the end product has the molecular formula. Isomers themselves exist in many varieties but can generally be classified as structural isomers or stereoisomers, structural isomers have a different ordering of bonds and/or different bond connectivity from one another, as in the case of hexane and its four other isomeric forms. Stereoisomers have the same ordering of bonds and the same connectivity. For example, 2-butene exists in two forms, cis-2-butene and trans-2-butene. The sub-categories of isomerases containing racemases, epimerases and cis-trans isomers are examples of enzymes catalyzing the interconversion of stereoisomers, intramolecular lyases, oxidoreductases and transferases catalyze the interconversion of structural isomers. The prevalence of each isomer in nature depends in part on the isomerization energy, isomers close in energy can interconvert easily and are often seen in comparable proportions. Isomerases can increase the rate by lowering the isomerization energy. Calculating isomerase kinetics from experimental data can be more difficult than for other enzymes because the use of product inhibition experiments is impractical, There are also practical difficulties in determining the rate-determining step at high concentrations in a single isomerization. Instead, tracer perturbation can overcome these technical difficulties if there are two forms of the unbound enzyme and this technique uses isotope exchange to measure indirectly the interconversion of the free enzyme between its two forms. The radiolabeled substrate and product diffuse in a time-dependent manner, when the system reaches equilibrium the addition of unlabeled substrate perturbs or unbalances it. As equilibrium is established again, the substrate and product are tracked to determine energetic information. This technique was adopted to study the profile of proline racemase. Generally, the names of isomerases are formed as substrate isomerase, enzyme-catalyzed reactions each have a uniquely assigned classification number. Isomerase-catalyzed reactions have their own EC category, EC5, Isomerases are further classified into six subclasses, This category includes and epimerases)
5.
Reaction rate
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The reaction rate or speed of reaction for a reactant or product in a particular reaction is intuitively defined as how quickly or slowly a reaction takes place. Chemical kinetics is the part of chemistry that studies reaction rates. The concepts of chemical kinetics are applied in many disciplines, such as engineering, enzymology. Consider a typical reaction, a A + b B → p P + q Q The lowercase letters represent stoichiometric coefficients, while the capital letters represent the reactants. Reaction rate usually has the units of mol L−1 s−1, the rate of a reaction is always positive. A negative sign is present to indicate that the reactant concentration is decreasing. )The IUPAC recommends that the unit of time should always be the second. The rate of reaction differs from the rate of increase of concentration of a product P by a constant factor and for a reactant A by minus the reciprocal of the stoichiometric number. The stoichiometric numbers are included so that the rate is independent of which reactant or product species is chosen for measurement. For example, if a =1 and b =3 then B is consumed three times more rapidly than A, but v = -d/dt = -d/dt is uniquely defined. The above definition is valid for a single reaction, in a closed system of constant volume. If water is added to a pot containing salty water, the concentration of salt decreases, although there is no chemical reaction. When applied to the system at constant volume considered previously, this equation reduces to, r = d d t. Here N0 is the Avogadro constant, for a single reaction in a closed system of varying volume the so-called rate of conversion can be used, in order to avoid handling concentrations. It is defined as the derivative of the extent of reaction with respect to time, also V is the volume of reaction and Ci is the concentration of substance i. When side products or reaction intermediates are formed, the IUPAC recommends the use of the rate of appearance and rate of disappearance for products and reactants. Reaction rates may also be defined on a basis that is not the volume of the reactor, when a catalyst is used the reaction rate may be stated on a catalyst weight or surface area basis. If the basis is a specific catalyst site that may be counted by a specified method. The nature of the reaction, Some reactions are faster than others
6.
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
7.
Diffusion limited enzyme
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A Diffusion limited enzyme is an enzyme which catalyses a reaction so efficiently that the rate limiting step is that of substrate diffusion into the active site, or product diffusion out. This is also known as kinetic perfection or catalytic perfection, since the rate of catalysis of such enzymes is set by the diffusion-controlled reaction, it therefore represents an intrinsic, physical constraint on evolution. Diffusion limited perfect enzymes are very rare, most enzymes catalyse their reactions to a rate that is 1, 000-10,000 times slower than this limit. This is due to both the limitations of difficult reactions, and the evolutionary limitations that such high reaction rates do not confer any extra fitness. The theory of diffusion-controlled reaction was utilized by R. A. Alberty, Gordon Hammes, and Manfred Eigen to estimate the upper limit of enzyme-substrate reaction, according to their estimation, the upper limit of enzyme-substrate reaction was 109 M−1 s−1. To address such a paradox, Prof, the new upper limit found by Chou et al. for enzyme-substrate reaction was further discussed and analyzed by a series of follow-up studies. Kinetically perfect enzymes have a specificity constant, kcat/Km, on the order of 108 to 109 M−1 s−1, the rate of the enzyme-catalysed reaction is limited by diffusion and so the enzyme processes the substrate well before it encounters another molecule. Some enzymes operate with kinetics which are faster than diffusion rates, several mechanisms have been invoked to explain this phenomenon. Some proteins are believed to accelerate catalysis by drawing their substrate in, some invoke a quantum-mechanical tunneling explanation whereby a proton or an electron can tunnel through activation barriers, although proton tunneling remains a somewhat controversial idea. It is worth noting that there are not many kinetically perfect enzymes and this can be explained in terms of natural selection. An increase in speed may be favoured as it could confer some advantage to the organism. However, when the catalytic speed outstrips diffusion speed there is no advantage to increase the speed even further. The diffusion limit represents a physical constraint on evolution. Increasing the catalytic speed past the speed will not aid the organism in any way
8.
Nonlinear regression
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The data are fitted by a method of successive approximations. The data consist of independent variables, x, and their associated observed dependent variables. Each y is modeled as a variable with a mean given by a nonlinear function f. Systematic error may be present but its treatment is outside the scope of regression analysis, if the independent variables are not error-free, this is an errors-in-variables model, also outside this scope. This function is nonlinear because it cannot be expressed as a combination of the two β s. Other examples of nonlinear functions include exponential functions, logarithmic functions, trigonometric functions, power functions, Gaussian function, some functions, such as the exponential or logarithmic functions, can be transformed so that they are linear. When so transformed, standard linear regression can be performed but must be applied with caution, see Linearization, below, for more details. In general, there is no closed-form expression for the best-fitting parameters, usually numerical optimization algorithms are applied to determine the best-fitting parameters. Again in contrast to linear regression, there may be many local minima of the function to be optimized, in practice, estimated values of the parameters are used, in conjunction with the optimization algorithm, to attempt to find the global minimum of a sum of squares. For details concerning nonlinear data modeling see least squares and non-linear least squares, the assumption underlying this procedure is that the model can be approximated by a linear function. F ≈ f 0 + ∑ j J i j β j where J i j = ∂ f ∂ β j and it follows from this that the least squares estimators are given by β ^ ≈ −1 J T y. The nonlinear regression statistics are computed and used as in linear regression statistics, the linear approximation introduces bias into the statistics. Therefore more caution than usual is required in interpreting statistics derived from a nonlinear model, the best-fit curve is often assumed to be that which minimizes the sum of squared residuals. This is the least squares approach, however, in cases where the dependent variable does not have constant variance, a sum of weighted squared residuals may be minimized, see weighted least squares. Each weight should ideally be equal to the reciprocal of the variance of the observation, some nonlinear regression problems can be moved to a linear domain by a suitable transformation of the model formulation. For example, consider the nonlinear regression problem y = a e b x U with parameters a and b, however, use of a nonlinear transformation requires caution. The influences of the values will change, as will the error structure of the model. These may not be desired effects, for Michaelis–Menten kinetics, the linear Lineweaver–Burk plot 1 v =1 V max + K m V max of 1/v against 1/ has been much used
9.
Allosteric regulation
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In biochemistry, allosteric regulation is the regulation of an enzyme by binding an effector molecule at a site other than the enzymes active site. The site to which the effector binds is termed the allosteric site, Allosteric sites allow effectors to bind to the protein, often resulting in a conformational change involving protein dynamics. Effectors that enhance the activity are referred to as allosteric activators. Allosteric regulations are an example of control loops, such as feedback from downstream products or feedforward from upstream substrates. Long-range allostery is especially important in cell signaling, Allosteric regulation is also particularly important in the cells ability to adjust enzyme activity. The term allostery comes from the Greek allos, other, and stereos and this is in reference to the fact that the regulatory site of an allosteric protein is physically distinct from its active site. Most allosteric effects can be explained by the concerted MWC model put forth by Monod, Wyman, and Changeux, or by the model described by Koshland, Nemethy. Both postulate that enzyme subunits exist in one of two conformations, tensed or relaxed, and that relaxed subunits bind substrate more readily than those in the tense state, the two models differ most in their assumptions about subunit interaction and the preexistence of both states. Thus, all subunits must exist in the same conformation, the model further holds that, in the absence of any ligand, the equilibrium favors one of the conformational states, T or R. The equilibrium can be shifted to the R or T state through the binding of one ligand to a site that is different from the active site. The sequential model of allosteric regulation holds that subunits are not connected in such a way that a change in one induces a similar change in the others. Thus, all enzyme subunits do not necessitate the same conformation, moreover, the sequential model dictates that molecules of a substrate bind via an induced fit protocol. In general, when a subunit randomly collides with a molecule of substrate, while such an induced fit converts a subunit from the tensed state to relaxed state, it does not propagate the conformational change to adjacent subunits. Instead, substrate-binding at one subunit only slightly alters the structure of other subunits so that their sites are more receptive to substrate. A morpheein is a structure that can exist as an ensemble of physiologically significant. Transitions between alternate morpheein assemblies involve oligomer dissociation, conformational change in the state, and reassembly to a different oligomer. The required oligomer disassembly step differentiates the morpheein model for allosteric regulation from the classic MWC, porphobilinogen synthase is the prototype morpheein. Ensemble models like the Ensemble Allosteric Model and Allosteric Ising Model assume that each domain of the system can adopt two states similar to the MWC model, molecular dynamics simulations can be used to estimate a systemss statistical ensemble so that it can be analyzed with the allostery landscape model
10.
Dean Burk
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Dean Burk was an American biochemist, a co-discoverer of biotin, medical researcher, and a cancer researcher at the Kaiser Wilhelm Institute and the National Cancer Institute. In 1934, he developed the Lineweaver–Burk plot together with Hans Lineweaver, Dean was the second of four sons born to Frederic Burk, the founder of the San Francisco Normal School, a preparatory school for teachers which eventually became San Francisco State University. He entered the University of California at Davis at the age of 15, a year later, he transferred to the University of California at Berkeley, where he received his B. S. in Entomology in 1923. Four years later he earned a Ph. D. in biochemistry, Burk joined the Department of Agriculture in 1929 working in the Fixed Nitrogen Research Laboratory. In 1939, he joined the Cancer Institute as a senior chemist and he was head of the cytochemistry laboratory when he retired in 1974. He also taught biochemistry at the Cornell University medical school from 1939 to 1941 and he was a research master at George Washington University. Burk was a friend and co-author with Otto Heinrich Warburg. He was a co-developer of the prototype of the Magnetic Resonance Scanner, Burk published more than 250 scientific articles in his lifetime. He later became head of the National Cancer Institutes Cytochemistry Sector in 1938, after retiring from the NCI in 1974, Dean Burk remained active. He devoted himself to his opposition to water fluoridation, according to Burk fluoridation is a form of public mass murder. Dean Burk argued on Dutch television against a water fluoridation proposal which was before the Dutch Parliament in the Netherlands and he also was an avid supporter of laetrile, a cancer treatment now regarded by the medical establishment as ineffective and potentially dangerous. For his work on photosynthesis, Dean Burk received the Hillebrand Prize in 1952, Dean Burk and Otto Heinrich Warburg discovered the photosynthesis I-quantum reaction that splits CO2 activated by respiration. For his techniques to distinguish between cells and those damaged by cancer, Dean Burk was awarded the Gerhard Domagk Prize in 1965
11.
Concentration
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In chemistry, concentration is the abundance of a constituent divided by the total volume of a mixture. Several types of mathematical description can be distinguished, mass concentration, molar concentration, number concentration, the term concentration can be applied to any kind of chemical mixture, but most frequently it refers to solutes and solvents in solutions. The molar concentration has variants such as concentration and osmotic concentration. To concentrate a solution, one must add more solute, or reduce the amount of solvent, by contrast, to dilute a solution, one must add more solvent, or reduce the amount of solute. Unless two substances are fully miscible there exists a concentration at which no further solute will dissolve in a solution, at this point, the solution is said to be saturated. If additional solute is added to a solution, it will not dissolve, except in certain circumstances. Instead, phase separation will occur, leading to coexisting phases, the point of saturation depends on many variables such as ambient temperature and the precise chemical nature of the solvent and solute. Concentrations are often called levels, reflecting the mental schema of levels on the axis of a graph. There are four quantities that describe concentration, The mass concentration ρ i is defined as the mass of a constituent m i divided by the volume of the mixture V, ρ i = m i V. The molar concentration c i is defined as the amount of a constituent n i divided by the volume of the mixture V, c i = n i V, however, more commonly the unit mol/L is used. The number concentration C i is defined as the number of entities of a constituent N i in a divided by the volume of the mixture V, C i = N i V. The volume concentration ϕ i is defined as the volume of a constituent V i divided by the volume of the mixture V, ϕ i = V i V. Being dimensionless, it is expressed as a number, e. g.0.18 or 18%, several other quantities can be used to describe the composition of a mixture. Note that these should not be called concentrations, normality is defined as the molar concentration c i divided by an equivalence factor f e q. Since the definition of the equivalence factor depends on context, IUPAC, the SI unit for molality is mol/kg. The mole fraction x i is defined as the amount of a constituent n i divided by the amount of all constituents in a mixture n t o t, x i = n i n t o t. However, the deprecated parts-per notation is used to describe small mole fractions. The mole ratio r i is defined as the amount of a constituent n i divided by the amount of all other constituents in a mixture
12.
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
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