Aconitase Inhibitors
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Aconitase Inhibitors
Aconitase (aconitate hydratase; ) is an enzyme that catalyses the stereo-specific isomerization of citrate to isocitrate via ''cis''- aconitate in the tricarboxylic acid cycle, a non-redox-active process. Image:Citrate wpmp.png, Image:Aconitic acid.svg, Image:isocitric acid.svg, Structure Aconitase has two slightly different structures, depending on whether it is activated or inactivated. In the inactive form, its structure is divided into four domains. Counting from the N-terminus, only the first three of these domains are involved in close interactions with the Fe-4Scluster, but the active site consists of residues from all four domains, including the larger C-terminal domain. The Fe-S cluster and a anion also reside in the active site. When the enzyme is activated, it gains an additional iron atom, creating a Fe-4Scluster. However, the structure of the rest of the enzyme is nearly unchanged; the conserved atoms between the two forms are in essentially the same po ...
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Stereochemistry
Stereochemistry, a subdiscipline of chemistry, studies the spatial arrangement of atoms that form the structure of molecules and their manipulation. The study of stereochemistry focuses on the relationships between stereoisomers, which are defined as having the same molecular formula and sequence of bonded atoms (constitution) but differing in the geometric positioning of the atoms in space. For this reason, it is also known as Three-dimensional space, 3D chemistry—the prefix "stereo-" means "three-dimensionality". Stereochemistry applies to all kinds of compounds and ions, Organic chemistry, organic and Inorganic chemistry, inorganic species alike. Stereochemistry affects Biochemistry, biological, Physical chemistry, physical, and supramolecular chemistry. Stereochemistry reactivity (chemistry), reactivity of the molecules in question (dynamic stereochemistry). History In 1815, Jean-Baptiste Biot's observation of optical activity marked the beginning of organic stereochemistr ...
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Iron-responsive Element-binding Protein
The iron-responsive element-binding proteins, also known as IRE-BP, IRBP, IRP and IFR , bind to iron-responsive elements (IREs) in the regulation of human iron metabolism. Function ACO1, or IRP1, is a bifunctional protein that functions as an iron-responsive element (IRE)-binding protein involved in the control of iron metabolism by binding mRNA to repress translation or degradation. It functions also as the cytoplasmic isoform of aconitase. Aconitases are iron-sulfur proteins that require a 4Fe-4S cluster for their enzymatic activity, in which they catalyze conversion of citrate to isocitrate. This structure was based on x-ray crystal diffraction. The resolution was 2.80 Å. This protein was harvested from the species ''Oryctolagus cuniculus'', more commonly known as a rabbit. This protein has a couple of conformational changes associated with it to explain the alternative functions as either mRNA regulator or as an enzyme. This information was obtained from the RCSB protein d ...
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Acetyl CoA
Acetyl-CoA (acetyl coenzyme A) is a molecule that participates in many biochemical reactions in protein, carbohydrate and lipid metabolism. Its main function is to deliver the acetyl group to the citric acid cycle (Krebs cycle) to be oxidized for energy production. Coenzyme A (CoASH or CoA) consists of a β-mercaptoethylamine group linked to pantothenic acid (vitamin B5) through an amide linkage and 3'-phosphorylated ADP. The acetyl group (indicated in blue in the structural diagram on the right) of acetyl-CoA is linked to the sulfhydryl substituent of the β-mercaptoethylamine group. This thioester linkage is a "high energy" bond, which is particularly reactive. Hydrolysis of the thioester bond is exergonic (−31.5 kJ/mol). CoA is acetylated to acetyl-CoA by the breakdown of carbohydrates through glycolysis and by the breakdown of fatty acids through β-oxidation. Acetyl-CoA then enters the citric acid cycle, where the acetyl group is oxidized to carbon dioxide and wat ...
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Oxaloacetate
Oxaloacetic acid (also known as oxalacetic acid or OAA) is a crystalline organic compound with the chemical formula HO2CC(O)CH2CO2H. Oxaloacetic acid, in the form of its conjugate base oxaloacetate, is a metabolic intermediate in many processes that occur in animals. It takes part in gluconeogenesis, the urea cycle, the glyoxylate cycle, amino acid synthesis, fatty acid synthesis and the citric acid cycle. Properties Oxaloacetic acid undergoes successive deprotonations to give the dianion: :HO2CC(O)CH2CO2H −O2CC(O)CH2CO2H + H+, pKa = 2.22 :−O2CC(O)CH2CO2H −O2CC(O)CH2CO2− + H+, pKa = 3.89 At high pH, the enolizable proton is ionized: :−O2CC(O)CH2CO2− −O2CC(O−)CHCO2− + H+, pKa = 13.03 The enol forms of oxaloacetic acid are particularly stable. Keto-enol tautomerization is catalyzed by the enzyme oxaloacetate tautomerase. ''trans''-Enol-oxaloacetate also appears when tartrate is the substrate for fumarase. Biosynthesis Oxaloacetate forms ...
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Carboxyl Group
In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is often written as or , sometimes as with R referring to an organyl group (e.g., alkyl, alkenyl, aryl), or hydrogen, or other groups. Carboxylic acids occur widely. Important examples include the amino acids and fatty acids. Deprotonation of a carboxylic acid gives a carboxylate anion. Examples and nomenclature Carboxylic acids are commonly identified by their trivial names. They often have the suffix ''-ic acid''. IUPAC-recommended names also exist; in this system, carboxylic acids have an ''-oic acid'' suffix. For example, butyric acid () is butanoic acid by IUPAC guidelines. For nomenclature of complex molecules containing a carboxylic acid, the carboxyl can be considered position one of the parent chain even if there are other substituents, such as 3-chloropropanoic acid. Alternately, it can be named as a " ...
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Citrate Zoom Final
Citric acid is an organic compound with the formula . It is a colorless weak organic acid. It occurs naturally in citrus fruits. In biochemistry, it is an intermediate in the citric acid cycle, which occurs in the metabolism of all aerobic organisms. More than two million tons of citric acid are manufactured every year. It is used widely as acidifier, flavoring, preservative, and chelating agent. A citrate is a derivative of citric acid; that is, the salts, esters, and the polyatomic anion found in solutions and salts of citric acid. An example of the former, a salt is trisodium citrate; an ester is triethyl citrate. When citrate trianion is part of a salt, the formula of the citrate trianion is written as or . Natural occurrence and industrial production Citric acid occurs in a variety of fruits and vegetables, most notably citrus fruits. Lemons and limes have particularly high concentrations of the acid; it can constitute as much as 8% of the dry weight of these fruits ...
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Arrow Pushing Aconitase Final Draft
An arrow is a fin-stabilized projectile launched by a bow. A typical arrow usually consists of a long, stiff, straight shaft with a weighty (and usually sharp and pointed) arrowhead attached to the front end, multiple fin-like stabilizers called fletchings mounted near the rear, and a slot at the rear end called a nock for engaging the bowstring. A container or bag carrying additional arrows for convenient reloading is called a quiver. The use of bows and arrows by humans predates recorded history and is common to most cultures. A craftsman who makes arrows is a fletcher, and one who makes arrowheads is an arrowsmith.Paterson ''Encyclopaedia of Archery'' p. 56 History The oldest evidence of likely arrowheads, dating to years ago, were found in Sibudu Cave, current South Africa.Backwell L, d'Errico F, Wadley L.(2008). Middle Stone Age bone tools from the Howiesons Poort layers, Sibudu Cave, South Africa. Journal of Archaeological Science, 35:1566–1580. Backwell L, Bradf ...
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Superoxide
In chemistry, a superoxide is a compound that contains the superoxide ion, which has the chemical formula . The systematic name of the anion is dioxide(1−). The reactive oxygen ion superoxide is particularly important as the product of the one-electron reduction of dioxygen , which occurs widely in nature. Molecular oxygen (dioxygen) is a diradical containing two unpaired electrons, and superoxide results from the addition of an electron which fills one of the two degenerate molecular orbitals, leaving a charged ionic species with a single unpaired electron and a net negative charge of −1. Both dioxygen and the superoxide anion are free radicals that exhibit paramagnetism. Superoxide was historically also known as "hyperoxide". Salts Superoxide forms salts with alkali metals and alkaline earth metals. The salts sodium superoxide (), potassium superoxide (), rubidium superoxide () and caesium superoxide () are prepared by the reaction of with the respect ...
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Fluoroacetic Acid
Fluoroacetic acid is an organofluorine compound with the chemical formula . It is a colorless solid that is noted for its relatively high toxicity. The conjugate base, fluoroacetate occurs naturally in at least 40 plants in Australia, Brazil, and Africa. It is one of only five known organofluorine-containing natural products. Toxicity Fluoroacetic acid is a harmful metabolite of some fluorine-containing drugs (median lethal dose, LD50 = 10 mg/kg in humans). The most common metabolic sources of fluoroacetic acid are fluoroamines and fluoroethers. Fluoroacetic acid can disrupt the Krebs cycle. The metabolite of fluoroacetic acid is Fluorocitric acid and is very toxic because it is not processable using aconitase in the Krebs cycle (where fluorocitrate takes place of citrate as the substrate). The enzyme is inhibited and the cycle stops working. In contrast with fluoroacetic acid, difluoroacetic acid and trifluoroacetic acid are far less toxic. Its p''K''a is 2.66, in contras ...
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Serine
Serine (symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α- amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − form under biological conditions), and a side chain consisting of a hydroxymethyl group, classifying it as a polar amino acid. It can be synthesized in the human body under normal physiological circumstances, making it a nonessential amino acid. It is encoded by the codons UCU, UCC, UCA, UCG, AGU and AGC. Occurrence This compound is one of the proteinogenic amino acids. Only the L- stereoisomer appears naturally in proteins. It is not essential to the human diet, since it is synthesized in the body from other metabolites, including glycine. Serine was first obtained from silk protein, a particularly rich source, in 1865 by Emil Cramer. Its name is derived from the Latin for silk, '' sericum''. Serine's structure was established in ...
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MRNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is created during the process of Transcription (biology), transcription, where an enzyme (RNA polymerase) converts the gene into primary transcript mRNA (also known as pre-mRNA). This pre-mRNA usually still contains introns, regions that will not go on to code for the final amino acid sequence. These are removed in the process of RNA splicing, leaving only exons, regions that will encode the protein. This exon sequence constitutes mature mRNA. Mature mRNA is then read by the ribosome, and the ribosome creates the protein utilizing amino acids carried by transfer RNA (tRNA). This process is known as Translation (biology), translation. All of these processes form part of the central dogma of molecular biology, which describes the flow of geneti ...
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Ribosome
Ribosomes () are molecular machine, macromolecular machines, found within all cell (biology), cells, that perform Translation (biology), biological protein synthesis (messenger RNA translation). Ribosomes link amino acids together in the order specified by the codons of messenger RNA molecules to form polypeptide chains. Ribosomes consist of two major components: the small and large ribosomal subunits. Each subunit consists of one or more ribosomal RNA molecules and many ribosomal proteins (). The ribosomes and associated molecules are also known as the ''translational apparatus''. Overview The sequence of DNA that encodes the sequence of the amino acids in a protein is transcribed into a messenger RNA (mRNA) chain. Ribosomes bind to the messenger RNA molecules and use the RNA's sequence of nucleotides to determine the sequence of amino acids needed to generate a protein. Amino acids are selected and carried to the ribosome by transfer RNA (tRNA) molecules, which enter the riboso ...
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