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Sphingosine
Sphingosine (2-amino-4-trans-octadecene-1,3-diol) is an 18-carbon amino alcohol with an unsaturated hydrocarbon chain, which forms a primary part of sphingolipids, a class of cell membrane lipids that include sphingomyelin, an important phospholipid. Functions Sphingosine can be phosphorylated in vivo via two kinases, sphingosine kinase type 1 and sphingosine kinase type 2. This leads to the formation of sphingosine-1-phosphate, a potent signaling lipid. Sphingolipid metabolites, such as ceramides, sphingosine and sphingosine-1-phosphate, are lipid signaling molecules involved in diverse cellular processes. Biosynthesis Sphingosine is synthesized from palmitoyl CoA and serine in a condensation required to yield dihydrosphingosine. Dehydrosphingosine is then reduced by NADPH to dihydrosphingosine (sphinganine), acylated to dihydroceramide finally oxidized by FAD to ceramide. Sphingosine is then solely formed via degradation of sphingolipid in the lysosome. See also * ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Sphingosine-1-phosphate
Sphingosine-1-phosphate (S1P) is a signaling sphingolipid, also known as lysosphingolipid. It is also referred to as a bioactive lipid mediator. Sphingolipids at large form a class of lipids characterized by a particular aliphatic aminoalcohol, which is sphingosine. Production S1P is formed from ceramide, which is composed of a sphingosine and a fatty acid. Ceramidase, an enzyme primarily present in plasma membrane, will convert ceramide to sphingosine. sphingosine is then phosphorylated by sphingosine kinase (SK) isoenzymes. There are two identified isoenzymes, SK1 and SK2. These two enzymes have different tissue distribution. SK1 is highly expressed in spleen, lung and leukocytes, while SK2 is highly expressed in liver and kidney. SK2 is located mainly in the mitochondria, nucleus and the endoplasmic reticulum whereas SK1 is mainly located in cytoplasm and the cell membrane. Metabolism and degradation S1P can be dephosphorylated to sphingosine by sphingosine phosphatases and ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Lipid Signaling
Lipid signaling, broadly defined, refers to any biological signaling event involving a lipid messenger that binds a protein target, such as a receptor, kinase or phosphatase, which in turn mediate the effects of these lipids on specific cellular responses. Lipid signaling is thought to be qualitatively different from other classical signaling paradigms (such as monoamine neurotransmission) because lipids can freely diffuse through membranes (''see osmosis''). One consequence of this is that lipid messengers cannot be stored in vesicles prior to release and so are often biosynthesized "on demand" at their intended site of action. As such, many lipid signaling molecules cannot circulate freely in solution but, rather, exist bound to special carrier proteins in serum. Sphingolipid second messengers Ceramide Ceramide (Cer) can be generated by the breakdown of sphingomyelin (SM) by sphingomyelinases (SMases), which are enzymes that hydrolyze the phosphocholine group from the sph ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Sphingosine Synthesis Corrected
Sphingosine (2-amino-4-trans-octadecene-1,3-diol) is an 18-carbon amino alcohol with an unsaturated hydrocarbon chain, which forms a primary part of sphingolipids, a class of cell membrane lipids that include sphingomyelin, an important phospholipid. Functions Sphingosine can be phosphorylated in vivo via two kinases, sphingosine kinase type 1 and sphingosine kinase type 2. This leads to the formation of sphingosine-1-phosphate, a potent signaling lipid. Sphingolipid metabolites, such as ceramides, sphingosine and sphingosine-1-phosphate, are lipid signaling molecules involved in diverse cellular processes. Biosynthesis Sphingosine is synthesized from palmitoyl CoA and serine in a condensation required to yield dihydrosphingosine. Dehydrosphingosine is then reduced by NADPH to dihydrosphingosine (sphinganine), acylated to dihydroceramide finally oxidized by FAD to ceramide. Sphingosine is then solely formed via degradation of sphingolipid in the lysosome. See also ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
SPHK2
Sphingosine kinase 2 is a protein that in humans is encoded by the SPHK2 gene. This gene encodes one of two sphingosine kinase isozymes that catalyze the phosphorylation of sphingosine into sphingosine 1-phosphate. Sphingosine 1-phosphate mediates many cellular processes including migration, proliferation and apoptosis, and also plays a role in several types of cancer by promoting angiogenesis and tumorigenesis. The encoded protein may play a role in breast cancer proliferation and chemoresistance. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. rovided by RefSeq, Aug 2011 Inhibitors * Opaganib Opaganib (ABC294640) is a drug which acts as an inhibitor of the enzyme sphingosine kinase 2. It is under development as a potential treatment agent for several different kinds of cancer Cancer is a group of diseases involving abnormal c ... References Further reading * * * * * * * * * * EC 2.7.1 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Sphingomyelin
Sphingomyelin (SPH, ˌsfɪŋɡoˈmaɪəlɪn) is a type of sphingolipid found in animal cell membranes, especially in the membranous myelin sheath that surrounds some nerve cell axons. It usually consists of phosphocholine and ceramide, or a ethanolamine, phosphoethanolamine head group; therefore, sphingomyelins can also be classified as sphingophospholipids. In humans, SPH represents ~85% of all sphingolipids, and typically make up 10–20 mol % of plasma membrane lipids. Sphingomyelin was first isolated by Germans, German chemist Johann Ludwig Wilhelm Thudichum, Johann L.W. Thudicum in the 1880s. The structure of sphingomyelin was first reported in 1927 as N-acyl-sphingosine-1-phosphorylcholine. Sphingomyelin content in mammals ranges from 2 to 15% in most tissues, with higher concentrations found in nerve tissues, red blood cells, and the ocular lenses. Sphingomyelin has significant structural and functional roles in the cell. It is a plasma membrane component and parti ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Amino Alcohol
In organic chemistry, alkanolamines are organic compounds that contain both hydroxyl () and amino (, , and ) functional groups on an alkane backbone. The term alkanolamine is a broad class term that is sometimes used as a subclassification. Methanolamine.svg, methanolamine, an intermediate in the reaction of ammonia with formaldehyde Ethanolamine.png, Ethanolamine 2-amino-2-methyl-1-propanol.svg, 2-amino-2-methyl-1-propanol is a precursor to oxazolines valinol.svg, valinol is derived from the amino acid valine Sphingosine structure.svg, Sphingosine is a component of some cell membrane. 1-Aminoalcohols 1-Aminoalcohols are better known as hemiaminals. Methanolamine is the simplest member. 2-Aminoalcohols Key members: ethanolamine, dimethylethanolamine, ''N''-methylethanolamine, Aminomethyl propanol Two popular drugs, often called alkanolamine beta blockers, are members of this structural class: propranolol, pindolol. Isoetarine is yet another medicinally useful derivative o ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Palmitoyl CoA
Palmitoyl-CoA is an acyl-CoA thioester. It is an "activated" form of palmitic acid and can be transported into the mitochondrial matrix by the carnitine shuttle system (which transports fatty acyl-CoA molecules into the mitochondria), and once inside can participate in beta-oxidation. Alternatively, palmitoyl-CoA is used as a substrate in the biosynthesis of sphingosine (this biosynthetic pathway does not require transfer into the mitochondria). Biosynthesis Palmitoyl CoA formed from palmitic acid, in the reaction below. Palmitate + CoA-SH + ATP -> Palmitoyl-CoA + AMP + Pyrophosphate This reaction is often referred to as the "activation" of a fatty acid. The activation is catalyzed by palmitoyl-coenzyme A synthetase and the reaction proceeds through a two step mechanism, in which palmitoyl-AMP is an intermediate. The reaction is driven to completion by the exergonic hydrolysis of pyrophosphate. The activation of fatty acids occurs in the cytosol and beta-oxidation occ ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Kinases
In biochemistry, a kinase () is an enzyme that catalysis, catalyzes the transfer of phosphate groups from High-energy phosphate, high-energy, phosphate-donating molecules to specific Substrate (biochemistry), substrates. This process is known as phosphorylation, where the high-energy adenosine triphosphate, ATP molecule donates a phosphate group to the substrate (biology), substrate molecule. This transesterification produces a phosphorylated substrate and Adenosine diphosphate, ADP. Conversely, it is referred to as dephosphorylation when the phosphorylated substrate donates a phosphate group and adenosine diphosphate, ADP gains a phosphate group (producing a dephosphorylated substrate and the high energy molecule of ATP). These two processes, phosphorylation and dephosphorylation, occur four times during glycolysis. Kinases are part of the larger family of phosphotransferases. Kinases should not be confused with phosphorylases, which catalyze the addition of inorganic phosphate ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Fingolimod
Fingolimod, sold under the brand name Gilenya, is an immunomodulating medication, mostly used for treating multiple sclerosis (MS). Fingolimod is a sphingosine-1-phosphate receptor modulator, which sequesters lymphocytes in lymph nodes, preventing them from contributing to an autoimmune reaction. It has been reported to reduce the rate of relapses in relapsing-remitting multiple sclerosis by approximately one-half over a two-year period. Medical uses Fingolimod is used in the treatment of the relapsing form of multiple sclerosis. Its effect in those with primary progressive MS is not clear. It may also be used in chronic inflammatory demyelinating polyneuropathy. Adverse effects The most common side effects of fingolimod have been head colds, headache, increased gamma-glutamyl transfer (≤15%), diarrhea (13%), nausea (13%), abdominal pain (11%) and fatigue. A few cases of skin cancer have been reported, which has also been reported in patients taking natalizumab (Tysabri), ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ceramide
Ceramides are a family of waxy lipid molecules. A ceramide is composed of N-acetylsphingosine and a fatty acid. Ceramides are found in high concentrations within the cell membrane of eukaryotic cells, since they are component lipids that make up sphingomyelin, one of the major lipids in the lipid bilayer. Contrary to previous assumptions that ceramides and other sphingolipids found in cell membrane were purely supporting structural elements, ceramide can participate in a variety of cellular signaling: examples include regulating differentiation, proliferation, and programmed cell death (PCD) of cells. The word ''ceramide'' comes from the Latin ''cera'' (wax) and ''amide''. Ceramide is a component of vernix caseosa, the waxy or cheese-like white substance found coating the skin of newborn human infants. Pathways for ceramide synthesis There are three major pathways of ceramide generation. First, the sphingomyelinase pathway uses an enzyme to break down sphingomyelin in the ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
