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  1. 1. GLYCOLIPIDS<br />
  2. 2. They are lipids that contain carbohydrate <br />residues with sphingosine as the alcohol <br />and a very long-chain fatty acid (24 carbon <br />series). They are present in cerebral tissue, <br />therefore are called cerebrosides<br /> Definition: <br />
  3. 3. Carbohydrate and lipid components.<br />Derivatives of ceramide.<br />Essential components of all membranes, greatest amount in nerve tissue.<br />Interact with the extracellular environment.<br />No phospholipid but oligo or mono-saccharide attached to ceramide by O-glycosidic bond.<br />
  4. 4. Glycosphingolipids are antigenic, for example;<br /> blood group antigen.<br /> various embryonic antigens.<br /> tumor antigen.<br />The carbohydrate portion of a glycolipid is the <br />antigenic determinant.<br />Glycolipids also serve as cell surface receptor for <br />cholera and tetanus toxins and for certain viruses and <br />Microbes.<br />
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  6. 6. Classification of Glycosphingolipids<br />Classification of glycolipids depend on the number<br /> and type of carbohydrate moieties present.<br />Neutral glycosphingolipids :-<br />cerebrosides: ceramidemonosacharides that <br />contain either a molecule of galactose or glucose, <br />found predominately in the brain and peripheral <br />nervous tissue with high concentration in the myeline<br />sheath.<br />Galactocerebroside : Cer-Gal<br />Glucocerebroside : Cer-Glc<br />
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  8. 8. Globosides: ceramide oligosaccharide <br />attached by additional monosacharides<br />(galactoseN-acetylgalactosamineNac ) to<br />glucocerebroside<br />Lactosylceramide : Cer-Glc-Gal<br />Frossman antigen: Cer-Glc-Gal-Gal-GalNac-GalNac<br />
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  10. 10. Acidic glycosphingolipids:-<br />Negatively charged at physiological pH due to N-<br />acetylneuraminicacid (NANA) or sulfate group.<br />1. Ganglioside:ceramideoligosacharides with one<br /> or more molecule of NANA, found primarily in the <br />ganglion cells of the CNS, patricularly at the nerve <br />endings.<br />The gangliosides (G) are divided according to the <br />number of NANA molecule present in its structure <br />into, Gm ,Gd, Gt, Gq.<br />
  11. 11. They are more complex glycolipids that occur in the <br />gray matter of the brain, ganglion cells, and RBCs. <br /> They transfer biogenic amines across the cell <br />membrane and act as a cell membrane receptor. <br />Gangliosides contain;<br />sialic acid (N-acetylneuraminicacid),<br />ceramide (sphingosine + fatty acid of 18-24 carbon <br />atom length), Three molecules of hexoses (1 glucose + <br />2 galactose) and hexosamine. <br />The most simple type of it the monosialoganglioside,. <br /> It works as a receptor for cholera toxin in the human <br />intestine.<br />
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  14. 14. Sulfatides: cerebrosides that contain <br />sulfated galactosylresidues , found predominantly<br />in nerve tissue and kidney.<br />sulfate group is usually attached to the OH <br />group of C3 or C6 of galactose.<br />
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  17. 17. Synthesis of Neutral Glycosphingolipids<br />Sequential addition of glycosyl monomers transferred from UDP-sugar donor to the acceptor molecule.<br />Site – golgi apparatus<br />Subtrates – Ceramide, sugar activated by UDP<br />Galactocerobrosides – Ceramide + UDP- galactose<br />Glucocerebrosides – Ceramide + UDP – glucose<br />Enzymes – Glycosyltransferases<br />
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  19. 19. Synthesis of Acidic Glycosphingolipids<br />Gangliosides--- ceramide + two or more UDP-<br /> sugars react together to form Globoside. <br />NANA combines with globoside to form <br />Ganglioside.<br />Sulfatides----- 3´-hydroxyl group of <br />galactocerebroside gets a sulphate group from a <br />sulphate carrier, 3´-phosphoadenosine-5´-<br />phosphosulfate (PAPS) with the help of <br />sulfotransferaseand forms a sulfatide.<br />Galactocerebroside 3-sulfate is the major sulfatide<br /> in the brain.<br />
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  21. 21. phosphatidylcholine<br /> UDP-galactose UDP-glucose UDP – <br />diacylglycerol<br />UDP UDP sugars<br />SphingomyelinGalactocerebrosideGlucocerebrosidegloboside<br />CMP-NANA<br /> PAPS<br />CMP<br />Sulfatide<br />Ganglioside<br />Ceramide<br />
  22. 22. Degradation of glycosphingolipids<br />Glycosphingolipids are internalized by endocytosis.<br />Done by lysosomal enzymes.<br />Lysosomal enzymes hydrolytically and irreversibly <br />cleave specific bonds in the glycolipids.<br />The degradation is a sequential process following the rule “ last on, first off “ in which the last group added during synthesis is the first group removed in degradation.<br />