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Sphingosine Kinase
Sphingosine kinase (SphK) is a conserved lipid kinase that catalyzes formation sphingosine-1-phosphate (S1P) from the precursor sphingolipid sphingosine. Sphingolipid metabolites, such as ceramide, sphingosine and sphingosine-1-phosphate, are lipid second messengers involved in diverse cellular processes. There are two forms of SphK, SphK1 and SphK2. SphK1 is found in the cytosol of eukaryotic cells, and migrates to the plasma membrane upon activation. SphK2 is localized to the nucleus. Function S1P has been shown to regulate diverse cellular processes. It has been characterized as a lipid signaling molecule with dual function. On one hand, it exerts its actions extracellularly by binding to the five different S1P receptors that couple to a variety of G-proteins to regulate diverse biological functions, ranging from cell growth and survival to effector functions, such as proinflammatory mediator synthesis. On the other hand, it appears to act as an intracellular second ...
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Sphingosine Kinase 1
Sphingosine kinase 1 is an enzyme that in humans is encoded by the ''SPHK1'' gene. Sphingosine kinase 1 phosphorylates sphingosine to sphingosine-1-phosphate (S1P) SK1 is normally a cytosolic protein but is recruited to membranes rich in phosphatidate (PA), a product of Phospholipase D (PLD) Sphingosine-1-phosphate (S1P) is a novel lipid messenger with both intracellular and extracellular functions. Intracellularly, it regulates proliferation and survival, and extracellularly, it is a ligand for EDG1. Various stimuli increase cellular levels of S1P by activation of sphingosine kinase (SPHK), the enzyme that catalyzes the phosphorylation of sphingosine. Competitive inhibitors of SPHK block formation of S1P and selectively inhibit cellular proliferation induced by a variety of factors, including platelet-derived growth factor and serum. Interactions SPHK1 has been shown to interact with TRAF2 TNF receptor-associated factor 2 is a protein that in humans is encoded by the ' ...
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Sphingolipid
Sphingolipids are a class of lipids containing a backbone of sphingoid bases, a set of aliphatic amino alcohols that includes sphingosine. They were discovered in brain extracts in the 1870s and were named after the mythological sphinx because of their enigmatic nature. These compounds play important roles in signal transduction and cell recognition. Sphingolipidoses, or disorders of sphingolipid metabolism, have particular impact on neural tissue. A sphingolipid with an R group consisting of a hydrogen atom only is a ceramide. Other common R groups include phosphocholine, yielding a sphingomyelin, and various sugar monomers or dimers, yielding cerebrosides and globosides, respectively. Cerebrosides and globosides are collectively known as glycosphingolipids. Structure The long-chain bases, sometimes simply known as sphingoid bases, are the first non-transient products of '' de novo'' sphingolipid synthesis in both yeast and mammals. These compounds, specifically known as phy ...
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Josiah Bartlet
Josiah Edward "Jed" Bartlet is a fictional character from the American television serial drama ''The West Wing'' created by Aaron Sorkin and portrayed by actor Martin Sheen. The role earned Sheen a Golden Globe Award for Best Actor – Television Series Drama in 2001, as well as two SAG Awards. Bartlet's tenure as a fictional Democratic President of the United States is a preeminent aspect of the series. His origin as a recurring character evolved due to Sheen's acting finesse; Sorkin and fellow ''West Wing'' writers shaped Bartlet's role within the show accordingly. The first season depicts part of Bartlet's first two years in the White House. The remainder of the series flesh out the details of Bartlet's administration, including friction between his policies and those of the Republican-dominated Congress, his tribulations with multiple sclerosis, his reelection, and the campaign of his successor, Matt Santos. Bartlet is characterized by manifest integrity, quick witt ...
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The West Wing
''The West Wing'' is an American serial (radio and television), serial political drama television series created by Aaron Sorkin that was originally broadcast on NBC from September 22, 1999, to May 14, 2006. The series is set primarily in the West Wing of the White House, where the Oval Office and offices of presidential senior personnel are located, during the fictitious Democratic Party (United States), Democratic administration of President Josiah Bartlet. ''The West Wing'' was produced by Warner Bros. Television and featured an List of The West Wing characters, ensemble cast, including Martin Sheen, John Spencer (actor), John Spencer, Allison Janney, Rob Lowe, Bradley Whitford, Richard Schiff, Janel Moloney, Dulé Hill, and Stockard Channing. For the first four seasons, there were three executive producers: Sorkin (lead writer of the first four seasons), Thomas Schlamme (primary director), and John Wells (TV producer), John Wells. After Sorkin left the series, Wells assume ...
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The West Wing (season 3)
The third season of the American political drama television series ''The West Wing'' aired in the United States on NBC from October 3, 2001 to May 22, 2002 and consisted of 21 episodes and 2 special episodes. Production The season premiere was delayed by the September 11 attacks, September 11, 2001 terrorist attacks in the United States. When the season did return, the first episode was a special episode titled "Isaac and Ishmael," in which the main cast paid tribute to those affected by the attacks and informed viewers about what to expect from the delayed premiere. Series creator Aaron Sorkin acknowledged in October 2002 that the terrorism-related plots designed to keep the series relevant after the real-life attacks were awkward at times, saying "from week to week, you felt like you were writing the show handcuffed, a little bit. I didn't know how to write it anymore. It was a constant search for what I wasn't doing that used to make the show work. Maybe there was a way to ma ...
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Carbohydrate
In organic chemistry, a carbohydrate () is a biomolecule consisting of carbon (C), hydrogen (H) and oxygen (O) atoms, usually with a hydrogen–oxygen atom ratio of 2:1 (as in water) and thus with the empirical formula (where ''m'' may or may not be different from ''n''), which does not mean the H has covalent bonds with O (for example with , H has a covalent bond with C but not with O). However, not all carbohydrates conform to this precise stoichiometric definition (e.g., uronic acids, deoxy-sugars such as fucose), nor are all chemicals that do conform to this definition automatically classified as carbohydrates (e.g. formaldehyde and acetic acid). The term is most common in biochemistry, where it is a synonym of saccharide (), a group that includes sugars, starch, and cellulose. The saccharides are divided into four chemical groups: monosaccharides, disaccharides, oligosaccharides, and polysaccharides. Monosaccharides and disaccharides, the smallest (lower molecular wei ...
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Phosphocholine
Phosphocholine is an intermediate in the synthesis of phosphatidylcholine in tissues. Phosphocholine is made in a reaction, catalyzed by choline kinase, that converts ATP and choline into phosphocholine and ADP. Phosphocholine is a molecule found, for example, in lecithin. In nematodes and human placentas, phosphocholine is selectively attached to other proteins as a posttranslational modification to suppress an immune response by their hosts. It is also one of the binding targets of C-reactive protein (CRP). Thus, when a cell is damaged, CRP binds to phosphocholine, beginning the recognition and phagocytotic immunologic response. Phosphocholine is a natural constituent of hens' eggs (and many other eggs) often used in biomimetic membrane studies. See also * Alkylphosphocholines * Choline * Phosphoethanolamine Phosphorylethanolamine or phosphoethanolamine is an ethanolamine derivative that is used to construct two different categories of phospholipids. One category ...
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Amide
In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it is part of the main chain of a protein, and an isopeptide bond when it occurs in a side chain, such as in the amino acids asparagine and glutamine. It can be viewed as a derivative of a carboxylic acid () with the hydroxyl group () replaced by an amine group (); or, equivalently, an acyl (alkanoyl) group () joined to an amine group. Common examples of amides are acetamide (), benzamide (), and dimethylformamide (). Amides are qualified as primary, secondary, and tertiary according to whether the amine subgroup has the form , , or , where R and R' are groups other than hydrogen. The core of amides is called the amide group (specifically, carboxamide group). Amides are pervasive in nature and technology. Proteins and important plastics l ...
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Fatty Acid
In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, from 4 to 28. Fatty acids are a major component of the lipids (up to 70% by weight) in some species such as microalgae but in some other organisms are not found in their standalone form, but instead exist as three main classes of esters: triglycerides, phospholipids, and cholesteryl esters. In any of these forms, fatty acids are both important dietary sources of fuel for animals and important structural components for cells. History The concept of fatty acid (''acide gras'') was introduced in 1813 by Michel Eugène Chevreul, though he initially used some variant terms: ''graisse acide'' and ''acide huileux'' ("acid fat" and "oily acid"). Types of fatty acids Fatty acids are classified in many ways: by length, by saturation vs unsaturati ...
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Sphinganine
Safingol is a lyso-sphingolipid protein kinase inhibitor. It has the molecular formula C18H39NO2 and is a colorless solid. Medicinally, safingol has demonstrated promising anticancer potential as a modulator of multi-drug resistance and as an inducer of necrosis. The administration of safingol alone has not been shown to exert a significant effect on tumor cell growth.Schwartz, G. K., Haimovitz-Friedman, A., Dhupar, S. K., Ehleiter, D., Maslak, P., Lai, L., ... & Albino, A. P. (1995). Potentiation of apoptosis by treatment with the protein kinase C-specific inhibitor safingol in mitomycin C-treated gastric cancer cells. Journal of the National Cancer Institute, 87(18), 1394-1399. However, preclinical and clinical studies have shown that combining safingol with conventional chemotherapy agents such as fenretinide, vinblastine, irinotecan and mitomycin C can dramatically potentiate their antitumor effects. Currently in Phase I clinical trials, it is believed to be safe to co-admini ...
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