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AICA Ribonucleotide
5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR) is an intermediate in the generation of inosine monophosphate. AICAR is an analog of adenosine monophosphate (AMP) that is capable of stimulating AMP-dependent protein kinase (AMPK) activity. The drug has also been shown as a potential treatment for diabetes by increasing the metabolic activity of tissues by changing the physical composition of muscle. Mechanism of action The nucleoside form of AICAR, acadesine, is an analog of adenosine that enters cardiac cells to inhibit adenosine kinase and adenosine deaminase. It enhances the rate of nucleotide re-synthesis increasing adenosine generation from adenosine monophosphate only during conditions of myocardial ischemia. In cardiac myocytes, acadesine is phosphorylated to AICAR to activate AMPK without changing the levels of the nucleotides. AICAR is able to enter the de novo synthesis pathway for adenosine synthesis to inhibit adenosine deaminase causing an increase in ATP level ...
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Inosine Monophosphate
Inosinic acid or inosine monophosphate (IMP) is a nucleotide (that is, a nucleoside monophosphate). Widely used as a flavor enhancer, it is typically obtained from chicken byproducts or other meat industry waste. Inosinic acid is important in metabolism. It is the ribonucleotide of hypoxanthine and the first nucleotide formed during the synthesis of purine nucleotides. It can also be formed by the deamination of adenosine monophosphate by AMP deaminase. It can be hydrolysis, hydrolysed to inosine. The enzyme deoxyribonucleoside triphosphate pyrophosphohydrolase, encoded by YJR069C in ''Saccharomyces cerevisiae'' and containing (d)ITPase and (d)XTPase activities, hydrolyzes inosine triphosphate (ITP) releasing pyrophosphate and IMP. Important derivatives of inosinic acid include the purine nucleotides found in nucleic acids and adenosine triphosphate, which is used to store chemical energy in muscle and other tissues. In the food industry, inosinic acid and its salt (chemistry), ...
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Structural Analog
A structural analog (analogue in modern traditional English; Commonwealth English), also known as a chemical analog or simply an analog, is a compound having a structure similar to that of another compound, but differing from it in respect to a certain component. It can differ in one or more atoms, functional groups, or substructures, which are replaced with other atoms, groups, or substructures. A structural analog can be imagined to be formed, at least theoretically, from the other compound. Structural analogs are often isoelectronic. Despite a high chemical similarity, structural analogs are not necessarily functional analogs and can have very different physical, chemical, biochemical, or pharmacological properties. In drug discovery, either a large series of structural analogs of an initial lead compound are created and tested as part of a structure–activity relationship study or a database is screened for structural analogs of a lead compound. Chemical analogues of il ...
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Adenosine Monophosphate
Adenosine monophosphate (AMP), also known as 5'-adenylic acid, is a nucleotide. AMP consists of a phosphate group, the sugar ribose, and the nucleobase adenine; it is an ester of phosphoric acid and the nucleoside adenosine. As a substituent it takes the form of the prefix adenylyl-. AMP plays an important role in many cellular metabolic processes, being interconverted to Adenosine diphosphate, ADP and/or Adenosine triphosphate, ATP. AMP is also a component in the synthesis of RNA. AMP is present in all known forms of life. Production and degradation AMP does not have the high energy phosphoanhydride bond associated with ADP and ATP. AMP can be produced from Adenosine diphosphate, ADP: : 2 ADP → ATP + AMP Or AMP may be produced by the hydrolysis of one high energy phosphate bond of ADP: : ADP + H2O → AMP + phosphate, Pi AMP can also be formed by hydrolysis of Adenosine triphosphate, ATP into AMP and pyrophosphate: : ATP + H2O → AMP + pyrophosphate, PPi When RNA i ...
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AMP-activated Protein Kinase
5' AMP-activated protein kinase or AMPK or 5' adenosine monophosphate-activated protein kinase is an enzyme (EC 2.7.11.31) that plays a role in cellular energy homeostasis, largely to activate glucose and fatty acid uptake and oxidation when cellular energy is low. It belongs to a highly conserved eukaryotic protein family and its orthologues are SNF1 in yeast, and SnRK1 in plants. It consists of three proteins ( subunits) that together make a functional enzyme, conserved from yeast to humans. It is expressed in a number of tissues, including the liver, brain, and skeletal muscle. In response to binding AMP and ADP, the net effect of AMPK activation is stimulation of hepatic fatty acid oxidation, ketogenesis, stimulation of skeletal muscle fatty acid oxidation and glucose uptake, inhibition of cholesterol synthesis, lipogenesis, and triglyceride synthesis, inhibition of adipocyte lipogenesis, inhibition of adipocyte lipolysis, and modulation of insulin secretion by pancreatic β ...
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Nucleoside
Nucleosides are glycosylamines that can be thought of as nucleotides without a phosphate group. A nucleoside consists simply of a nucleobase (also termed a nitrogenous base) and a five-carbon sugar (ribose or 2'-deoxyribose) whereas a nucleotide is composed of a nucleobase, a five-carbon sugar, and one or more phosphate groups. In a nucleoside, the anomeric carbon is linked through a glycosidic bond to the N9 of a purine or the N1 of a pyrimidine. Nucleotides are the molecular building-blocks of DNA and RNA. List of nucleosides and corresponding nucleobases The reason for 2 symbols, shorter and longer, is that the shorter ones are better for contexts where explicit disambiguation is superfluous (because context disambiguates) and the longer ones are for contexts where explicit disambiguation is judged to be needed or wise. For example, when discussing long nucleobase sequences in genomes, the CATG symbol system is much preferable to the Cyt-Ade-Thy-Gua symbol system (see '' N ...
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Acadesine
Acadesine (INN), also known as 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside, AICA-riboside, and AICAR, is an AMP-activated protein kinase activator which is used for the treatment of acute lymphoblastic leukemia and may have applications in treating other disorders such as diabetes. AICAR has been used clinically to treat and protect against cardiac ischemic injury. The drug was first used in the 1980s as a method to preserve blood flow to the heart during surgery. Acadesine is an adenosine regulating agent developed by PeriCor Therapeutics and licensed to Schering-Plough in 2007 for phase III studies. The drug is a potential first-in-class agent for prevention of reperfusion injury in CABG surgery. Schering began patient enrollment in phase III studies in May 2009. The trial was terminated in late 2010 based on an interim futility analysis. Chemistry Reaction of 2-bromo tribenzoyl ribose with diaminomaleonitrile results in the displacement of the anomeric halogen by one ...
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Adenosine
Adenosine ( symbol A) is an organic compound that occurs widely in nature in the form of diverse derivatives. The molecule consists of an adenine attached to a ribose via a β-N9-glycosidic bond. Adenosine is one of the four nucleoside building blocks of RNA (and its derivative deoxyadenosine is a building block of DNA), which are essential for all life. Its derivatives include the energy carriers adenosine mono-, di-, and triphosphate, also known as AMP/ADP/ATP. Cyclic adenosine monophosphate (cAMP) is pervasive in signal transduction. Adenosine is used as an intravenous medication for some cardiac arrhythmias. Adenosyl (abbreviated Ado or 5'-dAdo) is the chemical group formed by removal of the 5′-hydroxy (OH) group. It is found in adenosylcobalamin (an active form of vitamin B12) and as a radical in radical SAM enzymes. Medical uses Supraventricular tachycardia In individuals with supraventricular tachycardia (SVT), adenosine is used to help identify and convert the rhyt ...
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Nucleotide
Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules within all life-forms on Earth. Nucleotides are obtained in the diet and are also synthesized from common nutrients by the liver. Nucleotides are composed of three subunit molecules: a nucleobase, a five-carbon sugar (ribose or deoxyribose), and a phosphate group consisting of one to three phosphates. The four nucleobases in DNA are guanine, adenine, cytosine and thymine; in RNA, uracil is used in place of thymine. Nucleotides also play a central role in metabolism at a fundamental, cellular level. They provide chemical energy—in the form of the nucleoside triphosphates, adenosine triphosphate (ATP), guanosine triphosphate (GTP), cytidine triphosphate (CTP) and uridine triphosphate (UTP)—throughout the cell for the many cellular func ...
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Myocytes
A muscle cell is also known as a myocyte when referring to either a cardiac muscle cell (cardiomyocyte), or a smooth muscle cell as these are both small cells. A skeletal muscle cell is long and threadlike with many nuclei and is called a muscle fiber. Muscle cells (including myocytes and muscle fibers) develop from embryonic precursor cells called myoblasts. Myoblasts fuse to form multinucleated skeletal muscle cells known as syncytia in a process known as myogenesis. Skeletal muscle cells and cardiac muscle cells both contain myofibrils and sarcomeres and form a striated muscle tissue. Cardiac muscle cells form the cardiac muscle in the walls of the heart chambers, and have a single central nucleus. Cardiac muscle cells are joined to neighboring cells by intercalated discs, and when joined in a visible unit they are described as a ''cardiac muscle fiber''. Smooth muscle cells control involuntary movements such as the peristalsis contractions in the esophagus and stomach. Sm ...
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De Novo Synthesis
In chemistry, ''de novo'' synthesis () refers to the synthesis of complex molecules from simple molecules such as sugars or amino acids, as opposed to recycling after partial degradation. For example, nucleotides are not needed in the diet as they can be constructed from small precursor molecules such as formate and aspartate. Methionine, on the other hand, is needed in the diet because while it can be degraded to and then regenerated from homocysteine, it cannot be synthesized ''de novo''. Nucleotide ''De novo'' pathways of nucleotides do not use free bases: adenine (abbreviated as A), guanine (G), cytosine (C), thymine (T), or uracil (U). The purine ring is built up one atom or a few atoms at a time and attached to ribose throughout the process. Pyrimidine ring is synthesized as orotate and attached to ribose phosphate and later converted to common pyrimidine nucleotides. Cholesterol Cholesterol is an essential structural component of animal cell membranes. Cholestero ...
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Agence Française De Lutte Contre Le Dopage
The French Anti-Doping Agency (, AFLD) is an independent public authority formed in 2006 and charged with ensuring that participants in sports in France do not violate rules regarding doping. As a national anti-doping organization ( NADO), the AFLD cooperates with the World Anti-Doping Agency (WADA) and with other signatory organizations of the World Anti-Doping Code such as international sports federations. The agency has been particularly prominent in cases involving the Tour de France, such as that of Floyd Landis, who was stripped of his title in the 2006 race. A breakdown in the relationship between AFLD and the Union Cycliste Internationale in relation to testing procedures in the 2009 Tour de France lead to the severance of the role which gave AFLD their highest profile cases. AFLD Departments * Testing Department * Department of legal and institutional affairs * Intelligence and investigation department * Education and prevention Assignments Anti-Doping testi ...
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2009 Tour De France
The 2009 Tour de France was the 96th edition of the Tour de France, one of cycling's Grand Tours. It started on 4 July in the principality of Monaco with a individual time trial which included a section of the Circuit de Monaco. The race visited six countries: Monaco, France, Spain, Andorra, Switzerland and Italy, and finished on 26 July on the Champs-Élysées in Paris. The total length was , including in time-trials. There were seven mountain stages, three of which had mountaintop finishes, and one medium-mountain stage. The race had a team time trial for the first time since 2005, the shortest distance in individual time trials since 1967, and the first penultimate-day mountain stage in the Tour's history. 2007 winner Alberto Contador won the race by a margin of 4′11″, having won both a mountain and time trial stage. His team also took the team classification. and supplied the initial third-place finisher, Lance Armstrong. Armstrong's achievement was later voided b ...
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