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.
Metabolism
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Metabolism is the set of life-sustaining chemical transformations within the cells of living organisms. These enzyme-catalyzed reactions allow organisms to grow and reproduce, maintain their structures, usually, breaking down releases energy and building up consumes energy. The chemical reactions of metabolism are organized into metabolic pathways, in one chemical is transformed through a series of steps into another chemical. Enzymes act as catalysts that allow the reactions to proceed more rapidly, enzymes also allow the regulation of metabolic pathways in response to changes in the cells environment or to signals from other cells. The metabolic system of a particular organism determines which substances it will find nutritious, for example, some prokaryotes use hydrogen sulfide as a nutrient, yet this gas is poisonous to animals. The speed of metabolism, the rate, influences how much food an organism will require. A striking feature of metabolism is the similarity of the metabolic pathways. These striking similarities in metabolic pathways are likely due to their appearance in evolutionary history. Most of the structures that make up animals, plants and microbes are made from three classes of molecule, amino acids, carbohydrates and lipids. These biochemicals can be joined together to make such as DNA and proteins. Proteins are made of amino acids arranged in a linear chain joined together by peptide bonds, many proteins are enzymes that catalyze the chemical reactions in metabolism. Other proteins have structural or mechanical functions, such as those that form the cytoskeleton, Proteins are also important in cell signaling, immune responses, cell adhesion, active transport across membranes, and the cell cycle. Lipids are the most diverse group of biochemicals and their main structural uses are as part of biological membranes both internal and external, such as the cell membrane, or as a source of energy. Lipids are usually defined as hydrophobic or amphipathic biological molecules but will dissolve in organic solvents such as benzene or chloroform, the fats are a large group of compounds that contain fatty acids and glycerol, a glycerol molecule attached to three fatty acid esters is called a triacylglyceride. Several variations on this structure exist, including alternate backbones such as sphingosine in the sphingolipids. Steroids such as cholesterol are another class of lipids. Carbohydrates are aldehydes or ketones, with hydroxyl groups attached. Carbohydrates are the most abundant biological molecules, and fill numerous roles, such as the storage and transport of energy, the basic carbohydrate units are called monosaccharides and include galactose, fructose, and most importantly glucose
3.
Beta-ketoacyl-ACP synthase
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In molecular biology, Beta-ketoacyl-ACP synthase EC2.3.1.41, is an enzyme involved in fatty acid synthesis. It results in the formation of acetoacetyl ACP, Beta-ketoacyl-ACP synthase is a highly conserved enzyme that is found in almost all life on earth as a domain in fatty acid synthase. FAS has two types, aptly named type I and II, type I is found in animals, fungi, and “lower eukaryotes. ”Type II is found in prokaryotes, plastids, and mitochondria. Beta-ketoacyl-ACP synthase III, perhaps the most well known of family of enzymes, catalyzes a Claisen condensation between acetyl CoA and malonyl ACP. The image below reveals how CoA fits in the site as a substrate of synthase III. Beta-ketoacyl-ACP synthases I and II only catalyze acyl-ACP reactions with malonyl ACP, synthases I and II are capable of producing long-chain acyl-ACPs. Both are efficient up to acyl-ACPs with a 14 carbon chain, type I FAS catalyzes all the reactions necessary to create palmitic acid, which is a necessary function in animals for metabolic processes, one of which includes the formation of sphingosines. Beta-ketoacyl synthase contains two protein domains, the active site is located between the N- and C-terminal domains. The N-terminal domain contains most of the involved in dimer formation. Analogously, beta-ketoacyl-ACP synthase in plants is found in type II FAS, the presence of similar ketoacyl synthases present in all living organisms point to a common ancestor. Further examination of beta-ketoacyl-ACP synthases I and II of E. coli revealed that both are homodimeric, but synthase II is slightly larger, however, even though they are both involved in fatty acid metabolism, they also have highly divergent primary structure. In synthase II, each consists of a five-stranded beta pleated sheet surrounded by multiple alpha helices. The active sites are close, only about 25 angstroms apart. Beta-ketoacyl-synthase’s mechanism is a topic of debate among chemists, many agree that Cys171 of the active site attacks acetyl ACPs carbonyl, and, like most enzymes, stabilizes the intermediate with other residues in the active site. ACP is subsequently eliminated, and it deprotonates His311 in the process, a thioester is then regenerated with the cysteine in the active site. Decarboxylation of a malonyl CoA that is also in the site initially creates an enolate. The enolate tautomerizes to a carbanion that attacks the thioester of the acetyl-enzyme complex, some sources speculate that an activated water molecule also resides in the active site as a means of hydrating the CO2oreleasedr of attacking C3 of malonyl CoA. Another proposed mechanism considers the creation of a transition state
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.
Aminolevulinic acid synthase
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The reaction is as follows, succinyl-CoA + glycine ⇌ δ-aminolevulinic acid + CoA + CO2 This enzyme is expressed in all non-plant eukaryotes and the α-class of proteobacteria. Other organisms produce ALA through a three enzyme pathway known as the Shemin pathway, ALA is synthesized through the condensation of glycine and succinyl-CoA. In humans, transcription of ALA synthase is tightly controlled by the presence of Fe2+-binding elements, there are two forms of ALA synthase in the body. One form is expressed in red blood cell precursor cells, whereas the other is ubiquitously expressed throughout the body, the red blood cell form is coded by a gene on chromosome x, whereas the other form is coded by a gene on chromosome 3. The disease X-linked sideroblastic anemia is caused by mutations in the ALA synthase gene on chromosome X, gain of function mutations in the erythroid specific ALA synthase gene have been shown recently to cause a previously unknown form of porphyria known as X-linked-dominant protoporphyria. PLP-dependent enzymes are prevalent because they are needed to transform amino acids into other resources, ALAS is a homodimer with similarly sized sub units and the active sites consisting of amino acid side chains such as arginine, threonine, and lysine exist at a subunity interface. The protein when extracted from R. spheroids contains 1600-folds and weighs about 80,000 daltons, enzymatic activity varies for different sources of the enzyme. The active sites of ALAS utilize three key amino acid chains, Arg-85 and Thr-430 and Lys-313. Before the reaction can begin, the PLP cofactor binds to the side chain to form a Schiff base that promotes attack by glycine substrate. Lysine acts as a base during this mechanism. In the detailed mechanism, the hydronium atoms that are added in come from a variety of residues in that offer hydrogen bonds to facilitate ALA synthesis. Protonation of the group of the intermediate by an active site histidine leads to loss of the carboxyl group. The last intermediate is finally reprotonated to produce ALA, dissociation of ALA from the enzyme is the rate limiting step of the enzymatic reaction and was shown to be depended upon a slow conformational change of the enzyme. The function of pyridoxal phosphate is to facilitate the removal of hydrogen, the location of this enzyme in biological systems is indicative of the feedback that it may receive. ALA Synthase has been found in bacteria, yeast, avian and mammalian liver and blood cells, the location of this enzyme in animal cells is within the mitochondria. ALA synthase is inhibited by hemin and glucose. ALAS1 and ALAS2 catalyze the first step in the process of heme synthesis and it is the first irreversible step and is also rate limiting. This means that the beginning of the formation of hemes is very intentional, for example, the two substrates, oxaloacetate and glycine, are highly produced by and utilized in other essential biological processes such as glycolysis and the TCA cycle
7.
Dihydrolipoyl transacetylase
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Dihydrolipoyl transacetylase is an enzyme component of the multienzyme pyruvate dehydrogenase complex. The pyruvate dehydrogenase complex is responsible for the decarboxylation step that links glycolysis to the citric acid cycle. This involves the transformation of pyruvate from glycolysis into acetyl-CoA which is used in the citric acid cycle to carry out cellular respiration. There are three different enzyme components in the pyruvate dehydrogenase complex, pyruvate dehydrogenase is responsible for the oxidation of pyruvate, dihydrolipoyl transacetylase transfers the acetyl group to coenzyme A, and dihydrolipoyl dehydrogenase regenerates the lipoamide. In humans, dihydrolipoyl transacetylase enzymatic activity resides in the pyruvate dehydrogenase complex component E2 that is encoded by the DLAT gene, the systematic name of this enzyme class is acetyl-CoA, enzyme N6-lysine S-acetyltransferase. Other names in use include, All dihydrolipoyl transacetylases have a unique multidomain structure consisting of,3 lipoyl domains, an interaction domain. Interestingly all the domains are connected by disordered, low complexity linker regions, depending on the species, multiple subunits of dihydrolipoyl transacetylase enzymes can arrange together into either a cubic or dodecahedral shape. The cubic core structure, found in such as Azotobacter vinelandii, is made up of 24 subunits total. The catalytic domains are assembled into trimers with the site located at the subunit interface. The topology of this active site is identical to that of chloramphenicol acetyltransferase. Eight of these trimers are then arranged into a truncated cube. The two main substrates, CoA and the lipoamide, are found at two opposite entrances of a 30 Å long channel which runs between the subunits and forms the catalytic center, CoA enters from the inside of the cube, and the lipoamide enters from the outside. The subunits are arranged in sets of three, similar to the trimers in the cubic shape, with each set making up one of the 20 dodecahedral vertices. Dihydrolipoyl transacetylase participates in the decarboxylation reaction that links glycolysis to the citric acid cycle. The various parts of cellular respiration take place in different parts of the cell, thus pyruvate dehydrogenase complexes are found in the mitochondria of eukaryotes. Pyruvate decarboxylation requires a few cofactors in addition to the enzymes that make up the complex, the first is thiamine pyrophosphate, which is used by pyruvate dehydrogenase to oxidize pyruvate and to form a hydroxyethyl-TPP intermediate. This intermediate is taken up by dihydrolipoyl transacetylase and reacted with a second lipoamide cofactor to generate an acetyl-dihydrolipoyl intermediate and this second intermediate can then be attacked by the nucleophilic sulfur attached to Coenzyme A, and the dihydrolipoamide is released. This results in the production of acetyl CoA, which is the end goal of pyruvate decarboxylation, the dihydrolipoamide is taken up by dihydrolipoyl dehydrogenase, and with the additional cofactors FAD and NAD+, regenerates the original lipoamide
8.
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
9.
N-Acetylglutamate synthase
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N-acetylglutamate synthase is an enzyme that catalyses the production of N-Acetylglutamate from glutamate and acetyl-CoA. NAG can be used in the production of ornithine and arginine, in mammals, NAGS is expressed primarily in the liver and small intestine, and is localized to the mitochondrial matrix. Most prokaryotes and lower eukaryotes produce NAG through orinithine acetyltransferase, which is part of a ‘cyclic’ ornithine production pathway, NAGS is therefore used in a supportive role, replenishing NAG reserves as required. In some plants and bacteria, however, NAGS catalyzes the first step in a ‘linear’ arginine production pathway, the protein sequences of NAGS between prokaryotes, lower eukaryotes and higher eukaryotes have shown a remarkable lack of similarity. Sequence identity between prokaryotic and eukaryotic NAGS is largely <30%, while sequence identity between lower and higher eukaryotes is ~20%, enzyme activity of NAGS is modulated by L-arginine, which acts as an inhibitor in plant and bacterial NAGS, but an effector in vertebrates. While the role of arginine as an inhibitor of NAG in ornithine and arginine synthesis is well understood, the currently accepted role of NAG in vertebrates is as an essential allosteric cofactor for CPS1, and therefore it acts as the primary controller of flux through the urea cycle. In this role, feedback regulation from arginine would act to signal NAGS that ammonia is plentiful within the cell, as it stands, the evolutionary journey of NAGS from essential synthetic enzyme to primary urea cycle controller is yet to be fully understood. Studies conducted using NAGS derived from Neisseria gonorrhoeae suggest that NAGS proceeds through the previously described one-step mechanism, in this proposal, the carbonyl group of acetyl-CoA is attacked directly by the α-amino nitrogen of glutamate. Inactivity of NAGS results in N-acetylglutamate synthase deficiency, a form of hyperammonemia, in many vertebrates, N-acetylglutamate is an essential allosteric cofactor of CPS1, the enzyme that catalyzes the first step of the urea cycle. Without NAG stimulation, CPS1 cannot convert ammonia to carbamoyl phosphate, carbamoyl glutamate has shown promise as a possible treatment for NAGS deficiency. This is suspected to be a result of the similarities between NAG and carabamoyl glutamate, which allows carbamoyl glutamate to act as an effective agonist for CPS1
10.
Choline acetyltransferase
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Choline acetyltransferase is a transferase enzyme responsible for the synthesis of the neurotransmitter acetylcholine. ChAT catalyzes the transfer of a group from the coenzyme, acetyl-CoA. ChAT is found in concentration in cholinergic neurons, both in the central nervous system and peripheral nervous system. As with most of nerve terminal proteins, ChAT is produced in the body of the neuron and is transported to the nerve terminal, presence of ChAT in a nerve cell classifies this cell as a cholinergic neuron. In humans, the choline acetyltransferase enzyme is encoded by the CHAT gene, Choline acetyltransferase was first described by David Nachmansohn and A. L. Machado in 1943. Based on prior research showing that acetylcholines actions on structural proteins were responsible for nerve impulses, Nachmansohn, an enzyme has been extracted from brain and nervous tissue which forms acetylcholine. The formation occurs only in presence of adenosinetriphosphate, the enzyme is called choline acetylase. It was not until 1945 that Coenzyme A was discovered simultaneously and independently by three laboratories, Nachmansohns being one of these, subsequently acetyl-CoA, at the time called “active acetate, ” was discovered in 1951. The 3D structure of rat-derived ChAT was not solved until nearly 60 years later, the 3D structure of ChAT has been solved by X-ray crystallography PDB, 2FY2. The choline substrate fits into a pocket in the interior of ChAT, the 3D crystal structure shows the acetyl group of acetyl-CoA abuts the choline binding pocket – minimizing the distance between acetyl-group donor and receiver. ChAT is very conserved across the animal genome, among mammals, in particular, there is very high sequence similarity. Human and cat ChAT, for example, have 89% sequence identity, sequence identity with Drosophila is about 30%. There are two forms of ChAT, Soluble form and membrane-bound form, the soluble form accounts for 80-90% of the total enzyme activity while the membrane-bound form is responsible for the rest of 10-20% activity. However, there has long been a debate on how the form of ChAT is bound to the membrane. The membrane-bound form of ChAT is associated with synaptic vesicles, there exist two isoforms of ChAT, both encoded by the same sequence. The common type ChAT is present in both the CNS and PNS, peripheral type ChAT is preferentially expressed in the PNS in humans, and arises from exon skipping during post-transcriptional modification. Therefore, the amino acid sequence is similar, however pChAT is missing parts of the sequence present in cChAT. The pChAT isoform was discovered in 2000 based on observations that brain-derived ChAT antibodies failed to stain peripheral cholinergic neurons as they do for those found in the brain, cholinergic systems are implicated in numerous neurologic functions
