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Glossary linus pauling Institute oregon State University

rotolo ja, zhang j, donepudi m, lee h, fuks z, kolesnick r (2005). "Caspase-dependent and -independent activation of acid sphingomyelinase signaling". Dbaibo gs, el-Assaad w, krikorian a, liu b, diab k, idriss nz, el-Sabban m, driscoll ta, perry dk, hannun ya (2001). "Ceramide generation by two distinct pathways in tumor necrosis factor alpha-induced cell death". taha ta, mullen td, obeid lm (2006). "A house divided: ceramide, sphingosine, and sphingosine-1-phosphate in programmed cell death". hill jr, wertz pw (2009).

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More than one of pmc and pmc specified ( help ) li z, basterr mj, hailemariam tk, hojjati mr, lu s, liu j, liu r, zhou h, jiang xc mission (2005). "The effect of dietary sphingolipids on plasma sphingomyelin metabolism and atherosclerosis". Biochimica et biophysica Acta. mehra vc, jackson e, zhang xm, jiang xc, dobrucki lw, yu j, bernatchez p, sinusas aj, shulman gi, sessa wc, yarovinsky to, bender jr (2014). "Ceramide-activated phosphatase mediates fatty acid-induced endothelial vegf resistance and impaired angiogenesis". The American journal of Pathology. More than one of pmc and pmc specified ( help ) kogot-levin a, saada a (2014). "Ceramide and the mitochondrial respiratory chain". Dbaibo gs, pushkareva my, rachid ra, alter n, smyth mj, obeid lm, hannun ya (1998). "p53-dependent ceramide response to genotoxic stress".

wu d, ren z, pae m, guo w, cui x, merrill ah, meydani sn (2007). "Aging up-regulates expression of business inflammatory mediators in mouse adipose tissue". The journal of Immunology. a b Holland wl, bikman bt, wang lp, yuguang g, sargent km, bulchand s, knotts ta, shui g, clegg dj, wenk mr, pagliassotti mj, scherer pe, summers sa (2011). "Lipid-induced insulin resistance mediated by the proinflammatory receptor tlr4 requires saturated fatty acid-induced ceramide biosynthesis in mice". Journal of Clinical Investigation. More than one of pmc and pmc specified ( help ) Chavez ja, siddique mm, wang st, ching j, shayman ja, summers sa (2014). "Ceramides and glucosylceramides are independent antagonists of insulin signaling".

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The medical biochemistry page - official Site

32 The genus Sphingomonas however contain. References edit a b c haimovitz-Friedman a, kan cc, ehleiter d,. "Ionizing radiation acts on cellular membranes to generate ceramide and initiate apoptosis". a b Hannun,. "Principles of bioactive lipid signalling: lessons from sphingolipids". Nature reviews Molecular Cell biology. kitatani k, idkowiak-baldys j, hannun ya (2008). "The sphingolipid salvage pathway in ceramide metabolism and signaling". "Translational aspects of sphingolipid metabolism".

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19 A clinical trial using ceramide-rich wheat extract showed increased skin hydration in those taking the extract rather than the placebo. 20 Hormonal edit Increased ceramide synthesis leads to both leptin resistance and insulin resistance by increasing socs-3 expression. 21 An elevated level of ceramide results in the inhibition of the insulin signal transduction pathway and the serine phosphorylation of jnk, leading to insulin resistance. 22 Substances known to induce ceramide generation edit mechanism by which ceramide signaling occurs edit currently, the means by which ceramide acts as a signaling molecule are not clear. One hypothesis is that ceramide generated in the plasma membrane enhances membrane rigidity and stabilizes smaller lipid platforms known as lipid rafts, allowing them to serve as platforms for signalling molecules. Moreover, as rafts on one leaflet of the membrane can induce localized changes in the other leaflet of the bilayer, they can potentially serve as the link english between online signals from outside the cell to signals to be generated within the cell. Ceramide has also been shown to form organized large channels traversing the mitochondrial outer membrane.

This leads to the egress of proteins from the intermembrane space. Ceramides may be found as ingredients of some topical skin medications used to complement treatment for skin conditions such as eczema. 29 They are also used in cosmetic products such as some soaps, shampoos, skin creams, and sunscreens. 30 Additionally, ceramides are being explored as a potential therapeutic in cancer. 31 Ceramide in bacteria edit ceramide is rarely found in bacteria.

Ceramide accumulation has been found following treatment of cells with a number of apoptotic agents including ionizing radiation, 1 11 uv light, 12 tnf-alpha, 13 and chemotherapeutic agents. This suggests a role for ceramide in the biological responses of all these agents. Because of its apoptosis-inducing effects in cancer cells, ceramide has been termed the "tumor suppressor lipid". Several studies have attempted to define further the specific role of ceramide in the events of cell death and some evidence suggests ceramide functions upstream of the mitochondria in inducing apoptosis. However, owing to the conflicting and variable nature of studies into the role of ceramide in apoptosis, the mechanism by which this lipid regulates apoptosis remains elusive.

14 skin edit ceramide is the main component of the stratum corneum of the epidermis layer of human skin. 15 16 Together with cholesterol and saturated fatty acids, ceramide creates a water-impermeable, protective organ to prevent excessive water loss due to evaporation as well as a barrier against the entry of microorganisms. 16 In the hyperplastic disorder psoriasis the water permeability barrier is compromised. 17 The stratum corneum is composed of 50 ceramides, 25 cholesterol, and 15 free fatty acids. 17 key components of the extracellular lipid lamellae of the stratum corneum are ultra long chain (C28-C36) ceramides. 18 With aging there is a decline in ceramide and cholesterol in the stratum corneum of humans.

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4 5 Ceramides induce skeletal muscle insulin resistance when synthesized as a result of saturated fat activation of tlr4 receptors. 6 Unsaturated fat does not have this effect. 6 Ceramides induce insulin resistance in many tissues by inhibition of Akt/pkb signaling. 7 Aggregation of ldl cholesterol by ceramide causes ldl retention in arterial walls, leading to atherosclerosis. 8 Ceramides cause endothelial dysfunction by activating protein phosphatase 2 (PP2A). 9 In mitochondria, ceramide suppresses the electron transport chain and induces production of reactive oxygen species. 10 Apoptosis edit One of the most studied roles of ceramide pertains to its function as a proapoptotic molecule. Apoptosis, or Type i programmed cell death, is list essential for the maintenance of normal cellular homeostasis and is an important physiological response to many forms of cellular stress.

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Ceramide can be further hydrolyzed by acid ceramidase to form sphingosine and a free fatty acid, both of which are able to leave the lysosome, unlike ceramide. The long-chain sphingoid bases released from the lysosome may then re-enter pathways for synthesis of ceramide and/or sphingosine-1-phosphate. The salvage pathway re-utilizes long-chain sphingoid bases to form ceramide through the action of ceramide synthase. Thus, ceramide synthase family members probably trap free sphingosine released from the lysosome at the surface of the endoplasmic reticulum or in endoplasmic reticulum-associated membranes. It should also be noted that the salvage pathway has been estimated to contribute from 50 to 90 of sphingolipid biosynthesis. 3 Physiological roles edit As a bioactive lipid, ceramide has been implicated in a variety of physiological functions including apoptosis, cell growth arrest, differentiation, cell senescence, cell migration and adhesion. 2 Roles for ceramide and its downstream metabolites have also been suggested in a number of pathological pdf states including cancer, neurodegeneration, diabetes, microbial pathogenesis, obesity, and inflammation.

begins with the condensation of palmitate and serine to form 3-keto-dihydrosphingosine. This reaction is catalyzed by the enzyme serine palmitoyl transferase and is the rate-limiting step of the pathway. In turn, 3-keto-dihydrosphingosine is reduced to dihydrosphingosine, which is then followed by acylation by the enzyme (dihydro)ceramide synthase to produce dihydroceramide. The final reaction to produce ceramide is catalyzed by dihydroceramide desaturase. De novo synthesis of ceramide occurs in the endoplasmic reticulum. Ceramide is subsequently transported to the golgi apparatus by either vesicular trafficking or the ceramide transfer protein cert. Once in the golgi apparatus, ceramide can be further metabolized to other sphingolipids, such as sphingomyelin and the complex glycosphingolipids. 2 Salvage pathway edit constitutive degradation of sphingolipids and glycosphingolipids takes place in the acidic subcellular compartments, the late endosomes and the lysosomes, with the end goal of producing sphingosine. In the case of glycosphingolipids, exohydrolases acting at acidic pH optima cause the stepwise release of monosaccharide units from the end of the oligosaccharide chains, leaving just the sphingosine portion of the molecule, which may then contribute to the generation of ceramides.

Contents, pathways for ceramide synthesis edit, there are three major pathways of ceramide generation. The sphingomyelinase pathway uses an enzyme to break down sphingomyelin in the cell membrane and release ceramide. The de novo pathway creates ceramide from less complex molecules. Ceramide generation can also occur through breakdown of complex sphingolipids that are ultimately broken down into sphingosine, which is then reused by reacylation to form ceramide. This latter pathway is termed the salvage pathway. Sphingomyelin hydrolysis edit, hydrolysis of sphingomyelin is catalyzed by the enzyme sphingomyelinase. Because business sphingomyelin is one of the four common phospholipids found in the plasma membrane of cells, the implications of this method of generating ceramide is that the cellular membrane is the target of extracellular signals leading to programmed cell death.

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Ceramides are a family of waxy lipid molecules. A ceramide is composed of sphingosine and write 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. R represents the alkyl portion of a fatty acid.

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