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Uncoupling Agent
An uncoupler or uncoupling agent is a molecule that disrupts oxidative phosphorylation in prokaryotes and mitochondria or photophosphorylation in chloroplasts and cyanobacteria by dissociating the reactions of ATP synthesis from the electron transport chain. The result is that the cell or mitochondrion expends energy to generate a proton-motive force, but the proton-motive force is dissipated before the ATP synthase can recapture this energy and use it to make ATP. Uncouplers are capable of transporting protons through mitochondrial and lipid membranes. Description Classical uncouplers have five properties: # the complete release of respiratory control # the substitution of all coupled processes (ATP synthesis, transhydrogenation, reverse electron flow, active transport of cations, etc.) by a cyclic proton transport mediated by the uncoupler # the elimination of all protonic and cationic gradients generated across the mitochondrial or prokaryotic membrane # no discriminati ...
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Oxidative Phosphorylation
Oxidative phosphorylation (UK , US ) or electron transport-linked phosphorylation or terminal oxidation is the metabolic pathway in which cells use enzymes to oxidize nutrients, thereby releasing chemical energy in order to produce adenosine triphosphate (ATP). In eukaryotes, this takes place inside mitochondria. Almost all aerobic organisms carry out oxidative phosphorylation. This pathway is so pervasive because it releases more energy than alternative fermentation processes such as anaerobic glycolysis. The energy stored in the chemical bonds of glucose is released by the cell in the citric acid cycle producing carbon dioxide, and the energetic electron donors NADH and FADH. Oxidative phosphorylation uses these molecules and O2 to produce ATP, which is used throughout the cell whenever energy is needed. During oxidative phosphorylation, electrons are transferred from the electron donors to a series of electron acceptors in a series of redox reactions ending in oxygen, who ...
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BAM15
BAM15 is a novel mitochondrial protonophore uncoupler capable of protecting mammals from acute renal ischemic-reperfusion injury and cold-induced microtubule damage. References {{reflist External links Fat-fighting molecule sees the body burn more fuel Oxadiazoles Pyrazines Bicyclic compounds Fluoroarenes Anilines Secondary amines ...
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Secondary Metabolite
Secondary metabolites, also called specialised metabolites, toxins, secondary products, or natural products, are organic compounds produced by any lifeform, e.g. bacteria, fungi, animals, or plants, which are not directly involved in the normal growth, development, or reproduction of the organism. Instead, they generally mediate ecological interactions, which may produce a selective advantage for the organism by increasing its survivability or fecundity. Specific secondary metabolites are often restricted to a narrow set of species within a phylogenetic group. Secondary metabolites often play an important role in plant defense against herbivory and other interspecies defenses. Humans use secondary metabolites as medicines, flavourings, pigments, and recreational drugs. The term secondary metabolite was first coined by Albrecht Kossel, a 1910 Nobel Prize laureate for medicine and physiology in 1910. 30 years later a Polish botanist Friedrich Czapek described secondary metabolit ...
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Niclosamide
Niclosamide, sold under the brand name Niclocide among others, is an anthelmintic medication used to treat tapeworm infestations, including diphyllobothriasis, hymenolepiasis, and taeniasis. It is not effective against other worms such as flukes or roundworms. It is taken by mouth. Side effects include nausea, vomiting, abdominal pain, and itchiness. It may be used during pregnancy. It works by blocking glucose uptake and oxidative phosphorylation by the worm. Niclosamide was first synthesized in 1958. It is on the World Health Organization's List of Essential Medicines. Niclosamide is not available for human use in the United States. Side effects Side effects include nausea, vomiting, abdominal pain, constipation, and itchiness. Rarely, dizziness, skin rash, drowsiness, perianal itching, or an unpleasant taste occur. For some of these reasons, praziquantel is a preferable and equally effective treatment for tapeworm infestation. Important Note: Niclosamide kills the pork tap ...
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Flufenamic Acid
Flufenamic acid (FFA) is a member of the anthranilic acid derivatives (or fenamate) class of nonsteroidal anti-inflammatory drugs (NSAIDs). Like other members of the class, it is a cyclooxygenase (COX) inhibitor, preventing the formation of prostaglandins. FFA is known to bind to and reduce the activity of prostaglandin F synthase and activate TRPC6. It is not widely used in humans as it has a high rate (30–60%) of gastrointestinal side effects. It is generally not available in the US.NIH LiverTox DatabasMefenamic AcidLast updated June 23, 2015. Page accessed July 3, 2015. Quote: "(fenamates generally not available in the United States, such as tolfenamic acid and flufenamic acid)" It is available in some Asian and European countries as a generic drug. Scientists led by Claude Winder from Parke-Davis invented FFA in 1963, along with fellow members of the class, mefenamic acid in 1961 and meclofenamic acid Meclofenamic acid (used as meclofenamate sodium, brand name Meclo ...
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Ellipticine
Ellipticine is an alkaloid first extracted from trees of the species '' Ochrosia elliptica'' and ''Rauvolfia sandwicensis'', which inhibits the enzyme topoisomerase II via intercalative binding to DNA. Natural occurrence and synthesis Ellipticine is an organic compound present in several trees within the genera ''Ochrosia'', ''Rauvolfia'', ''Aspidosperma'', and ''Apocynaceae''. It was first isolated from '' Ochrosia elliptica'' Labill., a flowering tree native to Australia and New Caledonia which gives the alkaloid its name, in 1959, and synthesised by Robert Burns Woodward later the same year. Biological activity Ellipticine is a known intercalator, capable of entering a DNA strand between base pairs. In its intercalated state, ellipticine binds strongly and lies parallel to the base pairs, increasing the superhelical density of the DNA. Intercalated ellipticine binds directly to topoisomerase II, an enzyme involved in DNA replication, inhi ...
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Dinitro-ortho-cresol
Dinitro-''ortho''-cresol (DNOC) is an organic compound with the structural formula CH3C6H2(NO2)2OH. It is a yellow solid that is only slightly soluble in water. DNOC and some related derivatives have been used as herbicides. Preparation This compound is prepared by disulfonation of ''o''-cresol. The resulting disulfonate is then treated with nitric acid to give DNOC. A variety of related derivatives are known including those where the methyl group is replaced by ''sec''-butyl (dinoseb), ''tert''-butyl (dinoterb), and 1-methylheptyl ( dinocap). These are prepared by the direct nitration of the alkyphenols. Applications and safety This toxicant is an uncoupler, which means that it interferes with adenosine triphosphate (ATP) production. Symptoms of dinitro-''ortho''-cresol poisoning, due to ingestion or other forms of exposure, include confusion, headache, shortness of breath, and sweat Perspiration, also known as sweating, is the production of fluids secreted by the sweat ...
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Dicoumarol
Dicoumarol (INN) or dicumarol (USAN) is a naturally occurring anticoagulant drug that depletes stores of vitamin K (similar to warfarin, a drug that dicoumarol inspired). It is also used in biochemical experiments as an inhibitor of reductases. Dicoumarol is a natural chemical substance of combined plant and fungal origin. It is a derivative of coumarin, a bitter-tasting but sweet-smelling substance made by plants that does not itself affect coagulation, but which is (classically) transformed in mouldy feeds or silages by a number of species of fungi, into active dicoumarol. Dicoumarol does affect coagulation, and was discovered in mouldy wet sweet-clover hay, as the cause of a naturally occurring bleeding disease in cattle. See warfarin for a more detailed discovery history. Identified in 1940, dicoumarol became the prototype of the 4-hydroxycoumarin anticoagulant drug class. Dicoumarol itself, for a short time, was employed as a medicinal anticoagulant drug, but since the mid ...
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Desaspidin
Desaspidin is an anthelmintic. Desapidin may occur in natural form within some plants such as Coastal woodfern, ''Dryopteris arguta ''Dryopteris arguta'', with the common name coastal woodfern, is a species of wood fern. It is native to the west coast and western interior mountain ranges of North America, from British Columbia, throughout California, and into Arizona. It gr ...''. Since the 1950s the inhibition effects of desapidins upon phosphorylation in chloroplasts has been noted and studied. References Anthelmintics Cyclohexadienes Piceol ethers Resorcinols Propyl compounds {{antiinfective-drug-stub ...
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Carbonyl Cyanide-p-trifluoromethoxyphenylhydrazone
Carbonyl cyanide-''p''-trifluoromethoxyphenylhydrazone (FCCP) is an ionophore that is a mobile ion carrier. It is referred to as an uncoupling agent because it disrupts ATP synthesis by transporting hydrogen ions through the mitochondrial membrane before they can be used to provide the energy for oxidative phosphorylation. It is a nitrile and hydrazone Hydrazones are a class of organic compounds with the structure . They are related to ketones and aldehydes by the replacement of the oxygen =O with the = functional group. They are formed usually by the action of hydrazine on ketones or aldehydes. .... FCCP was first described in 1962 by Heytler. See also * Carbonyl cyanide ''m''-chlorophenyl hydrazone (CCCP) References {{reflist Ionophores Nitriles Trifluoromethyl ethers Uncoupling agents Hydrazones ...
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Carbonyl Cyanide M-chlorophenyl Hydrazone
Carbonyl cyanide ''m''-chlorophenyl hydrazone (CCCP; also known as 3-chlorophenyl)hydrazonoalononitrile) is a chemical inhibitor of oxidative phosphorylation. It is a nitrile, hydrazone and protonophore. In general, CCCP causes the gradual destruction of living cells and death of the organism, although mild doses inducing partial decoupling have been shown to increase median and maximum lifespan in '' C. elegans'' models, suggesting a degree of hormesis. CCCP causes an uncoupling of the proton gradient that is established during the normal activity of electron carriers in the electron transport chain. The chemical acts essentially as an ionophore and reduces the ability of ATP synthase to function optimally. It is routinely used as an experimental uncoupling agent in cell and molecular biology, particularly in the study of mitophagy, where it was integral in discovering the role of the Parkinson's disease-associated ubiquitin ligase Parkin. Outside of its effects on mitoch ...
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Phenylhydrazone
Hydrazones are a class of organic compounds with the structure . They are related to ketones and aldehydes by the replacement of the oxygen =O with the = functional group. They are formed usually by the action of hydrazine on ketones or aldehydes. Synthesis Hydrazine, organohydrazines, and 1,1-diorganohydrazines react with aldehydes and ketones to give hydrazones. : Phenylhydrazine reacts with reducing sugars to form hydrazones known as osazones, which was developed by German chemist Emil Fischer as a test to differentiate monosaccharides. Uses Hydrazones are the basis for various analyses of ketones and aldehydes. For example, dinitrophenylhydrazine coated onto a silica sorbent is the basis of an adsorption cartridge. The hydrazones are then eluted and analyzed by HPLC using a UV detector. The compound carbonyl cyanide-''p''-trifluoromethoxyphenylhydrazone (abbreviated as FCCP) is used to uncouple ATP synthesis and reduction of oxygen in oxidative phosphorylation in molec ...
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