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.
Nitrogen
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Nitrogen is a chemical element with symbol N and atomic number 7. It was first discovered and isolated by Scottish physician Daniel Rutherford in 1772, although Carl Wilhelm Scheele and Henry Cavendish had independently done so at about the same time, Rutherford is generally accorded the credit because his work was published first. Nitrogen is the lightest member of group 15 of the periodic table, the name comes from the Greek πνίγειν to choke, directly referencing nitrogens asphyxiating properties. It is an element in the universe, estimated at about seventh in total abundance in the Milky Way. At standard temperature and pressure, two atoms of the element bind to form dinitrogen, a colourless and odorless diatomic gas with the formula N2, dinitrogen forms about 78% of Earths atmosphere, making it the most abundant uncombined element. Nitrogen occurs in all organisms, primarily in amino acids, in the nucleic acids, the human body contains about 3% nitrogen by mass, the fourth most abundant element in the body after oxygen, carbon, and hydrogen. The nitrogen cycle describes movement of the element from the air, into the biosphere and organic compounds, many industrially important compounds, such as ammonia, nitric acid, organic nitrates, and cyanides, contain nitrogen. The extremely strong bond in elemental nitrogen, the second strongest bond in any diatomic molecule. Synthetically produced ammonia and nitrates are key industrial fertilisers, and fertiliser nitrates are key pollutants in the eutrophication of water systems. Apart from its use in fertilisers and energy-stores, nitrogen is a constituent of organic compounds as diverse as Kevlar used in high-strength fabric, Nitrogen is a constituent of every major pharmacological drug class, including antibiotics. Many notable nitrogen-containing drugs, such as the caffeine and morphine or the synthetic amphetamines. Nitrogen compounds have a long history, ammonium chloride having been known to Herodotus. They were well known by the Middle Ages, alchemists knew nitric acid as aqua fortis, as well as other nitrogen compounds such as ammonium salts and nitrate salts. The mixture of nitric and hydrochloric acids was known as aqua regia, celebrated for its ability to dissolve gold, the discovery of nitrogen is attributed to the Scottish physician Daniel Rutherford in 1772, who called it noxious air. Though he did not recognise it as a different chemical substance, he clearly distinguished it from Joseph Blacks fixed air. The fact that there was a component of air that does not support combustion was clear to Rutherford, Nitrogen was also studied at about the same time by Carl Wilhelm Scheele, Henry Cavendish, and Joseph Priestley, who referred to it as burnt air or phlogisticated air. Nitrogen gas was inert enough that Antoine Lavoisier referred to it as air or azote, from the Greek word άζωτικός. In an atmosphere of nitrogen, animals died and flames were extinguished
3.
Tyrosine aminotransferase
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Tyrosine aminotransferase is an enzyme present in the liver and catalyzes the conversion of tyrosine to 4-hydroxyphenylpyruvate. In humans, the tyrosine aminotransferase protein is encoded by the TAT gene, each side of the dimer protein includes pyridoxal phosphate bonded to the Lys280 residue of the tyrosine aminotransferase molecule. The amine group of attacks the alpha carbon of the imine bonded to Lys280, forming a tetrahedral complex. This process is known as transimination by the act of switching out the group bonded to PLP. The newly formed PLP-TYR molecule is then attacked by a base, a possible candidate for the base in the mechanism could be Lys280 that was just pushed off of PLP, which sequesters the newly formed amino group of the PLP-TYR molecule. In a similar mechanism of aspartate transaminase, the lysine that forms the initial imine to PLP later acts as the base that attacks the tyrosine in transimination. Water attacks the carbon of the imine of PLP-TYR and through acyl substitution kicks off the nitrogen of PLP. PMP is then regenerated into PLP by transferring its amine group to alpha-ketoglutarate and this is followed by another substitution reaction with the Lys280 residue to reform its imine linkage to the enzyme, forming ENZ-PLP. Tyrosine Aminotransferase as a dimer has two identical active sights, Lys280 is attached to PLP, which is held in place via two nonpolar amino acid side chains, phenylalanine and isoleucine. The PLP is also held in place by hydrogen bonding to surrounding molecules mainly by its phosphate group, shown below is one active site at three different magnifications, Tyrosinemia is the most common metabolic disease associated with tyrosine aminotransferase. The disease results from a deficiency in hepatic tyrosine aminotransferase, Tyrosinemia type II is a disease of autosomal recessive inheritance characterized by keratitis, palmoplantar hyperkeratosis, mental retardation, and elevated blood tyrosine levels. Keratitis in Tyrosinemia type II patients is caused by the deposition of crystals in the cornea. The TAT gene is located on human chromosome 16q22-24 and extends over 10.9 kilobases containing 12 exons, twelve different TAT gene mutations have been reported. Molecular graphics images were produced using the UCSF Chimera package from the Resource for Biocomputing, Visualization, tyrosine aminotransferase at the US National Library of Medicine Medical Subject Headings
4.
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
5.
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
6.
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
7.
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
8.
Glutamic acid
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Glutamic acid is an α-amino acid with formula C 5H 9O 4N. It is usually abbreviated as Glu or E in biochemistry and its molecular structure could be idealized as HOOC-CH-2-COOH, with two carboxyl groups -COOH and one amino group -NH2. However, in the state and mildly acid water solutions. Glutamic acid is used by almost all living beings in the biosynthesis of proteins and it is non-essential in humans, meaning the body can synthesize it. The acid can lose one proton from second carboxyl group to form the conjugate base and this form of the compound is prevalent in neutral solutions. The glutamate neurotransmitter plays the role in neural activation. This anion is also responsible for the flavor of certain foods. In highly alkaline solutions the doubly negative anion −OOC-CH-2-COO− prevails, the radical corresponding to glutamate is called glutamyl. When glutamic acid is dissolved in water, the group may gain a proton, and/or the carboxyl groups may lose protons. In sufficiently acid environments, the group gains a proton. At pH values between about 2.5 and 4.1, the carboxylic acid closer to the amine generally loses a proton, and the acid becomes the neutral zwitterion −OOC-CH-2-COOH. This is also the form of the compound in the solid state. The switchover is gradual, the two forms are in equal concentrations at pH2.10, at even higher pH, the other carboxyl loses its proton and the acid exists almost entirely as the glutamate anion −OOC-CH-2-COO−, with a single negative charge. The switchover occurs at pH4.07, the latter is the case, in particular, in the physiological pH range. At even higher pH, the group loses the extra proton. The switchover occurs at pH9.47, the carbon atom adjacent to the amino group is chiral, so glutamic acid can exist in two optical isomers, D and L. The L form is the one most widely occurring in nature, but the D form occurs in special contexts, such as the cell walls of the bacterium Escherichia coli. Although they occur naturally in foods, the flavor contributions made by glutamic acid
9.
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
10.
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
