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HETEROPOLYSACHARIDES

HETEROPOLYSACHARIDES. Dr SADIA HAROON. POLYSACCHARIDES – Most of the carbohydrates found in nature occur in the form of high molecular polymers called polysaccharides. Polysaccharides are of two types : Homopolysaccharides Heteropolysaccharides HOMOPOLYSACCHARIDES – polymer of same

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HETEROPOLYSACHARIDES

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  1. HETEROPOLYSACHARIDES Dr SADIA HAROON

  2. POLYSACCHARIDES – Most of the carbohydrates found in nature occur in the form of high molecular polymers called polysaccharides • Polysaccharides are of two types: • Homopolysaccharides • Heteropolysaccharides • HOMOPOLYSACCHARIDES – polymer ofsame • monosaccharideunits • eg : Starch, Glycogen, Inulin, Cellulose, Pectin,Chitin. • HETEROPOLYSACCHARIDES – polymer of different • monosaccharideunits • eg :Mucopolysaccharides

  3. DEFINITION:Heteropolysaccharides are High-molecular weight carbohydrate polymers more than one kind of monosaccharide. Chemically, they are formed mostly of repeated disaccharides units that contain amino sugar (N- acetyl glucosamine or N-acetyl galactosamine) uronic acid (glucuronic acid or its 5 epimer iduronic acid).

  4. Glycosaminoglycans andGlycoprotein • Objectives • Recognize the different classes of glycosaminoglycan and their functions. • Know what are the proteoglycans, function and the general • structure. • Glycoproteins and blood-group substances as example • *Glycosaminoglycan • -Structure • -classification • -Functions • *Glycoproteins • -structure and functions • -O- and N-linked oligosaccharides • -Blood group substances

  5. Most mammalian cells are located in tissues where they are surrounded by a complex extracellular matrix (ECM) often referred to as “connective tissue.” • Fibronectin is a protein in ECM bind fibrin ,heparin sulphate ,collagen and integrin which have binding sites of macromolecules . • Helps in spread of information between cell and ECM.

  6. Clinical importanceof GAGS AND GP • Lectins binds oligosacharide units on oute cell surface • Regulate degradation of peptide hormones • Circulating proteins and blood cells • Oligosacharide binds pathogens causing infection • Selectin mediate cell to matrix information transfer • Receiving and transformation from cell andecm. • Lysosomal diseases

  7. The ECM contains three major classes of biomolecules: (1) the structural proteins: collagen, elastin, and fibrillin; (2) certain specialized proteins such as fibrillin, fibronectin,and laminin; and (3) Proteoglycans

  8. Glycosaminoglycan (GAGs) are large complexes of negatively charged heteropolysaccharide chains. They are generally associated with a small amount of protein, forming proteoglycans, which typically consist of > 95% CHO. • Note: this is in comparison to the glycoproteins, which consist primarily of protein with a small amount of CHO

  9. Figure 14.2. Some monosaccharide units found in glycosaminoglycans.

  10. Overview of glycosaminoglycans Glycosaminoglycanshave the special ability to bind large amounts of water, thereby producing the gel-like matrix that forms the basis of the body’s ground substance • The viscous, lubricating properties of mucous secretions also result from the presence of GAGs, which led to the original naming of these as mucopolysaccharides

  11. Mucopolysaccharidesor Glycosaminoglycans(GAGs): • Glycosaminoglycans (GAGs) or mucopolysaccharides are long unbranched polysaccharides consisting of a repeating disaccharide unit. • GAGs-High-Molecular-weight carbohydrate polymers. Glycosaminoglycans forming the proteoglycans are the most abundant heteropolysaccharides in the body. • They are long unbranched molecules containing a repeating disaccharides unit. One or both sugars contain Sulfate Groups(the only exception is Hyaluronic acid).

  12. C. Structure of proteoglycans - All of the GAGs, except hyaluronic cid, are found covalently attached to proteins, forming proteoglycan monomers. 1. Structure of proteoglycan monomer: - A proteoglycan monomer found in cartilage consists of a core protein to which the linear GAG chains are covalently attached • These chains which may each be composed of >100 monosacch, extend out from the core protein & remain separated from each other because of charge repulsion. The resulting structure resembles a “bottle brush” • In cartilage proteoglycan, the species of GAGs include chondroitin sulfate & keratan sulfate

  13. PROTEOGLYCANS Note: a number of proteoglycans have been characterized & named based on their structure & functional location. E.g., syndecan is an integral memb proteoglycan, versican & aggrecan are the predominant extracellular proteoglycans, & neurocan & cerebrocan are found primarily in the NS.

  14. Figure 14.5. "Bottle-brush" model of a cartilage proteoglycan monomer.

  15. 2. Linkage between the carbohydrate chain & the protein • This linkage is most commonly through a trihexoside (galactose-galactose-xylose) & a ser residue, respectively. An O-glycosidic bond is formed b/w the xylose & the hydroxyl group of the ser.

  16. 3. Proteoglycan aggregates • The proteoglycan monomers associate with a molecule of hyaluronic acid to form proteoglycan aggregates. The association is not covalent, but occurs primarily through ionic interactions b/w core protein & the hyaluronic acid • The association is stabilized by additional small proteins called link proteins

  17. Figure 14.7. Proteoglycan aggregate.

  18. Hurler’s Syndrome(Mucopolysaccharidosis I)

  19. Facies of a male with the mucopolysaccharidosis, Hunter syndrome

  20. Function of Glycosaminoglycans.(GAGS) • They have the special ability to bind large amounts of water, there by producing the gel-like matrix • that forms the basis of the body’s ground substance. • Since they are negatively charged, for example, in bone, glycosaminoglycans attract and tightly bind cations like ca++, they also take-up Na+ and K+. • GAGs stabilize and support cellular and fibrous components of tissue while helping maintain the water and salt balance of the body.

  21. FUNCTIONS OF GAGS • Its essential components of the extra cellular matrix, GAGs play an important role in • mediating cell-cell interactions • Ground substance is a part of connective tissue, which is a gel like substance containing water, salt, proteins and polysaccharides. • An example of specialized ground substance is the synovial fluid, which serves as a lubricant in joints, and tendon sheaths.

  22. Functions: • Binding and packing of tissues (connective tissue proper) • Connect, anchor and support the body and its organs • Transport of metabolites between capillaries and tissues; • Heaparanssulphate bind large number of aggregates and bring cellular interactions.

  23. Defense against infection (via ground substance and cells) • Repair of injury (via cell proliferation and fiber formation) • Fat storage (as determined by age, sex, nutrition or disease)

  24. The extracellular space in animal tissues is filled with a gel-like material, the extracellular matrix, also called ground substance, • which holds the cells of a tissue together and provides a porous pathway for the diffusion of nutrients and oxygen to individual cells.

  25. Epithelial cells extra-cellularmatrix Underlying cells cells

  26. Strength and resilience • The extracellular matrix is composed of an interlocking meshwork of heteropolysaccharides and fibrous proteins. These are cross linked with fibrous matrix such as collagen,elastin,and fibronectin giving strength and resilience .

  27. Tissue organizer • They influence development of specialized tissues • Mediate the activities of growth factors • Regulate assembly of collagen fibres . • They are major component of cartilage and give them strength.

  28. Types: • GAGs are either sulfate group free or sulfate group containing • GAGs are sulfate group free(Hyaluronic acid) • GAGs are sulfate group containing as • Chondroitin sulfate • Heparin • Keratan sulfate and • Dermatan sulfate.

  29. GAGs ARE BOUND TO GLYCOPROTEIN APOPROTEINS : GLYCOPROTEIN (a protein to which sugars are bound) GLYCOPROTEINPROTEOGLYCAN (has bound oligosaccharides) (has GAGs bound to it) : a proteoglycan may refer to the holoprotein or the apoprotein (protein less the GAGs) and the literature is not always clear in making the distinction. HERE we will always refer to the holoprotein. Also glycoprotein may be general or refer to a protein bound to oligosaccharides.

  30. Structure ofGlycosaminoglycans Glycosaminoglycans (GAGs): large complexes of negatively charged linear heteropolysaccharides chains. These polymers consist of repeating disaccharide unit (acidic sugar-amino sugar). The amino sugar is either N- acetylglucosamine or N- acetylgalactosamine. The acidic sugar is–uronic acid usually D-glucouronic acid, some hydroxyl groups are esterified with sulfate. These compound have special ability to bind large amounts of water, so produce gel-like matrix

  31. Glucosaminoglycans • Heteropolysaccharides in the body are the glycosaminoglycans (GAGs). These molecules are long unbranched polysaccharides containing a repeating disaccharide unit.

  32. Structure of GAGS • GAGs are highly negatively charged molecules, with extended conformation that imparts high viscosity to the solution. • GAGs are located primarily on the surface of cells or in the extracellular matrix (ECM).

  33. Properties of GAGS • Along with the high viscosity of GAGs comes low compressibility, which makes these molecules ideal for a lubricating fluid in the joints.

  34. Rigidity and structural integrity • At the same time, their rigidity provides structural integrity to cells and provides passageways between cells, allowing for cell migration.

  35. Composition of GAGS • The disaccharide units contain either of two modified sugars, called amino sugarsN-acetylgalactosamine (GalNAc) or N-acetylglucosamine (GlcNAc), • and an acidic sugar uronic acid such as glucuronic acid or iduronic acid.

  36. The amino group is usually acetylated. • This eliminates the positive charge.

  37. Copmosition of GAGS • In some glycosaminoglycans, one or more of the hydroxyls of the amino sugar is esterified with sulfate. • The combination of these sulfate groups and the carboxylate groups of the uronic acid residues gives the glycosaminoglycans a very high density of negative charge.

  38. Keratan sulfate is an exception in which galactose is present, instead of an acidic sugar. • Hyaluronic acid does not contain sulfate.

  39. Structure of Glycosaminoglycans • GAGs in the body are linked to core proteins ( except hyaluronic acid), forming proteoglycans (also called mucopolysaccharides).

  40. The GAGs extend perpendicularly from the core in a brush-like structure. • E.g. in cartilage proteoglycan the GAGs present are chondriotin sulfate and keratan sulfate.

  41. Linkage • The linkage of GAGs to the protein core involves a specific trisaccharide composed of two galactose residues and a xylose residue (Gal-Gal-Xyl-O-CH2-protein).

  42. The trisaccharide linker is coupled to the protein core through an O-glycosidic bond to a Serine residue in the protein. • Some forms of keratan sulfates are linked to the protein core through an N-glycosidic bond.

  43. The protein cores of proteoglycans are rich in Serine and Threonine residues, which allows multiple GAG attachments.

  44. Proteoglycan Aggregates • Proteoglycan monomers associate with a molecule of hylauronic acid to form proteoglycan aggregates. • Association is not covalent but ionic between hyaluronic acid and the core protein. • Stabilized by link proteins

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