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PUGNAc
PUGNAc is a 1,5-hydroximolactone, acting as an inhibitor of a variety of N-acetylhexosaminidases. It was long thought that increased levels of ''O''-GlcNAc in human cells lead to Type II diabetes. O-GlcNAc levels were artificially raised with PUGNAc, which inhibits O-GlcNAcase, a beta-exo-N-acetylhexosaminidase which cleaves beta-O-linked-N-acetylglucosamine residues from glycoproteins. As a result of this inhibition, a type II diabetic phenotype was observed. Recent pharmacological studies using a more selective O-GlcNAcase inhibitor did not see this effect. However, genetic manipulation of O-GlcNAc levels is consistent with the effects observed by PUGNAc, namely insulin resistance upon elevation of O-GlcNAc levels. Fictional references PUGNAc was used by Michael Scofield in the television series ''Prison Break'' to keep his blood sugar Glycaemia, also known as blood sugar level, blood sugar concentration, or blood glucose level is the measure of glucose concentrated in ...
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O-GlcNAc
''O''-GlcNAc (short for ''O''-linked GlcNAc or ''O''-linked β-''N''-acetylglucosamine) is a reversible enzymatic post-translational modification that is found on serine and threonine residues of nucleocytoplasmic proteins. The modification is characterized by a β-glycosidic bond between the hydroxyl group of serine or threonine side chains and ''N''-acetylglucosamine (GlcNAc). ''O''-GlcNAc differs from other forms of protein glycosylation: (i) ''O''-GlcNAc is not elongated or modified to form more complex glycan structures, (ii) ''O''-GlcNAc is almost exclusively found on nuclear and cytoplasmic proteins rather than membrane proteins and secretory proteins, and (iii) ''O''-GlcNAc is a highly dynamic modification that turns over more rapidly than the proteins which it modifies. ''O''-GlcNAc is conserved across metazoans. Due to the dynamic nature of ''O''-GlcNAc and its presence on serine and threonine residues, ''O''-GlcNAcylation is similar to protein phosphorylation in some r ...
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Enzyme Inhibitor
An enzyme inhibitor is a molecule that binds to an enzyme and blocks its activity. Enzymes are proteins that speed up chemical reactions necessary for life, in which substrate molecules are converted into products. An enzyme facilitates a specific chemical reaction by binding the substrate to its active site, a specialized area on the enzyme that accelerates the most difficult step of the reaction. An enzyme inhibitor stops ("inhibits") this process, either by binding to the enzyme's active site (thus preventing the substrate itself from binding) or by binding to another site on the enzyme such that the enzyme's catalysis of the reaction is blocked. Enzyme inhibitors may bind reversibly or irreversibly. Irreversible inhibitors form a chemical bond with the enzyme such that the enzyme is inhibited until the chemical bond is broken. By contrast, reversible inhibitors bind non-covalently and may spontaneously leave the enzyme, allowing the enzyme to resume its function. Reve ...
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N-acetylhexosaminidases
Hexosaminidase (, ''beta-acetylaminodeoxyhexosidase'', ''N-acetyl-beta-D-hexosaminidase'', ''N-acetyl-beta-hexosaminidase'', ''N-acetyl hexosaminidase'', ''beta-hexosaminidase'', ''beta-acetylhexosaminidinase'', ''beta-D-N-acetylhexosaminidase'', ''beta-N-acetyl-D-hexosaminidase'', ''beta-N-acetylglucosaminidase'', ''hexosaminidase A'', ''N-acetylhexosaminidase'', ''beta-D-hexosaminidase'') is an enzyme involved in the hydrolysis of terminal N-acetyl-D-hexosamine residues in N-acetyl-β-D-hexosaminides. Elevated levels of hexosaminidase in blood and/or urine have been proposed as a biomarker of relapse in the treatment of alcoholism. Hereditary inability to form functional hexosaminidase enzymes are the cause of lipid storage disorders Tay-Sachs disease and Sandhoff disease. Isozymes and genes Lysosomal A, B, and S isozymes Functional lysosomal β-hexosaminidase enzymes are dimeric in structure. Three isozymes are produced through the combination of α and β subunits to ...
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Type II Diabetes
Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urination, and unexplained weight loss. Symptoms may also include increased hunger, feeling tired, and sores that do not heal. Often symptoms come on slowly. Long-term complications from high blood sugar include heart disease, strokes, diabetic retinopathy which can result in blindness, kidney failure, and poor blood flow in the limbs which may lead to amputations. The sudden onset of hyperosmolar hyperglycemic state may occur; however, ketoacidosis is uncommon. Type 2 diabetes primarily occurs as a result of obesity and lack of exercise. Some people are genetically more at risk than others. Type 2 diabetes makes up about 90% of cases of diabetes, with the other 10% due primarily to type 1 diabetes and gestational diabetes. In type 1 diabete ...
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Michael Scofield
Michael Scofield, portrayed by Wentworth Miller, is a fictional character and one of the two main protagonists of the American television series ''Prison Break''. The character first appeared in the series pilot, in which he deliberately goes to prison so as to break out his elder brother, Lincoln Burrows (Dominic Purcell), before his execution for a crime he did not commit. The storyline of the first season revolves around the two brothers and Michael's plan to help Lincoln escape his death sentence. Later seasons detail their life on the run and their quest for the truth behind Lincoln's imprisonment. As the principal character, Michael has been featured in every episode of the series. Although both Lincoln and Michael are the main protagonists of the series, Michael has been featured more extensively than Lincoln, especially in the first season and the third. Various flashbacks from subsequent episodes provide further insight into the relationship between Michael and his brot ...
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Prison Break
''Prison Break'' is an American serial (radio and television), serial drama television show, television series created by Paul Scheuring for Fox Broadcasting Company, Fox. The series revolves around two brothers, Lincoln Burrows (Dominic Purcell) and Michael Scofield (Wentworth Miller); Burrows has been sentenced to death for a crime he did not commit, while Scofield devises an elaborate plan to help his brother escape prison and clear his name. Along with creator Paul Scheuring, the series is executive-produced by Matt Olmstead, Kevin Hooks, Marty Adelstein, Dawn Parouse, Neal H. Moritz, and Brett Ratner who directed the pilot episode. The series' theme music, composed by Ramin Djawadi, was nominated for a Primetime Emmy Award in 2006. ''Prison Break'' is a joint production between Original Film, Adelstein/Parouse Productions (seasons 1–4), Dawn Olmstead Productions (season 5), Adelstein Productions (season 5), One Light Road Productions (season 5) and 20th Century Fox Televi ...
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Blood Sugar
Glycaemia, also known as blood sugar level, blood sugar concentration, or blood glucose level is the measure of glucose concentrated in the blood of humans or other animals. Approximately 4 grams of glucose, a simple sugar, is present in the blood of a 70 kg (154 lb) human at all times. The body tightly regulates blood glucose levels as a part of metabolic homeostasis. Glucose is stored in skeletal muscle and liver cells in the form of glycogen; in fasting individuals, blood glucose is maintained at a constant level at the expense of glycogen stores in the liver and skeletal muscle. In humans, a blood glucose level of 4 grams, or about a teaspoon, is critical for normal function in a number of tissues, and the human brain consumes approximately 60% of blood glucose in fasting, sedentary individuals. A persistent elevation in blood glucose leads to glucose toxicity, which contributes to cell dysfunction and the pathology grouped together as complications of diabetes. Gl ...
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Amino Sugars
In organic chemistry, an amino sugar (or more technically a 2-amino-2-deoxysugar) is a sugar molecule in which a hydroxyl group has been replaced with an amine group. More than 60 amino sugars are known, with one of the most abundant being ''N''-Acetyl--glucosamine, which is the main component of chitin. Derivatives of amine containing sugars, such as ''N''-acetylglucosamine and sialic acid, whose nitrogens are part of more complex functional groups rather than formally being amines, are also considered amino sugars. Aminoglycosides are a class of antimicrobial compounds that inhibit bacterial protein synthesis. These compounds are conjugates of amino sugars and aminocyclitols. Synthesis From glycals Glycals are cyclic enol ether derivatives of monosaccharides, having a double bond between carbon atoms 1 and 2 of the ring. ''N''-functionalized of glycals at the C2 position, combined with glycosidic bond formation at C1 is a common strategy for the synthesis of amino sugars. Th ...
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Carbamates
In organic chemistry, a carbamate is a category of organic compounds with the general formula and structure , which are formally derived from carbamic acid (). The term includes organic compounds (e.g., the ester ethyl carbamate), formally obtained by replacing one or more of the hydrogen atoms by other organic functional groups; as well as salts with the carbamate anion (e.g. ammonium carbamate). Polymers whose units are joined by carbamate groups are an important family of plastics, the polyurethanes. Properties While carbamic acids are unstable, many carbamate esters or ionic) are stable and well known. Equilibrium with carbonate and bicarbonate In water solutions, the carbamate anion slowly equilibrates with the ammonium cation and the carbonate or bicarbonate anions: : : Calcium carbamate is soluble in water, whereas calcium carbonate is not. Adding a calcium salt to an ammonium carbamate/carbonate solution will precipitate some calcium carbonate immediately, a ...
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