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Glycosaminoglycans and Glycoprotein 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 Glycosaminoglycans Glycosamines: sugar derivatives in which the hydroxyl group at C2 is replaced with NH2 group. Structure of Glycosaminoglycans 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 Nacetylglucosamine or Nacetylgalactosamine. 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 Functions of Glycosaminoglycans ∗ GAGs are component of the extracellular matrix; a gel-like material that fill the extracellular space in the tissues of multicellular animals. GAGs form an interlocking meshwork with the fibrous protein as fibronectin, collagen, elastin ∗ Responsible of the viscous, lubricant properties of mucous secretions and for this GAGs were called mucopolysaccharides ∗Stabilize and support cellular and fibrous component of the tissue; connective tissue (found in skin, tendons, cartilages….) they are consist of insoluble protein fibers distributed in the ground substance The character of the connective tissue is dependent on the relative proportions of the ground substance and embedded fibrous protein Classification of the Glycosaminoglycans They can be classified according to to their monomeric compositions, type of glycosidic linkages, and degree of their sulfate units. Glycoconjugates: Proteoglycans,Glycoproteins, and Glycolipids Polysaccharides are not only stored fuels and structural elements but also considered as information carriers - serve as destination markers for some protein -cell-cell recognition and adhesion, cell migration, blood clotting and immune response *The informational carbohydrates are usually covalently joined to a protein or lipid to form Glycoconjugate Glycoprteins: have one or several oligosaccharides of varying complexity joined covalently to proteins. They present at the outer side of the plasma membrane, extracellular matrix, and blood. Highly specific sites for recognition and high-affinity binding by other protein. Glycolipids: are membrane lipids, the hydrophilic head groups are oligsaccharides and act as specific sites for recognition by carbohydrate-binding proteins. Proteoglycans: macromolecules of cell surfaces or extracellular matrix in which glycosaminoglycan chains are joined covalently to a membrane protein. The glycosaminoglycan moiety forms the greater fraction of proteoglycanmolecule Glycoproteins Glycoproteins: are proteins to which oligosaccharides are covalently attached, the length of carbohydrate moiety is: relatively short compared to glycosaminoglycans, branched and may or may not negatively charged. Glycoproteins contain highly variable amounts of carbohydrates , IgG contains less than 4% Glycophorin (in the red blood cells) contains more than 20% Mucin (human gastric glycoprotein) contains more than 60% Advantages of adding oligosaccharides to proteins - Affects the polarity and solubility - affects the folding pathway of the proteinÎ affects the tertiary structure - each oligosaccharide represents a unique face that can be recognized by enzyme, signal and receptor which can interact with it Glycoproteins Functions: *membrane bound glycoproteins participate in many cellular phenomena including -cell surface recognition by other cells, hormones, viruses -cell surface antigenicity as blood group antigen *components of extracellular matrix, and of the mucins of the gastrointestinal tract and they act as protective biological lubricants. Structure of Glycoproteins The carbohydrate moiety is attached at its anomeric carbon through glycosidic link to the –OH of the serine or Threonine ( O-glycosidic link) or to the amide group of the Asparagine side chain(N-glycosidic link) A glycoprotein may contain N- and/ or O-linked glycosidic linkage O-linked oligosaccharides are found as membrane glycoprotein components or extracellular glycoproteins, e.g glycoprotein that provide ABO blood grouping N-linked oligosaccharides fall into two classes: complex oligosaccharides and high mannose oligosaccharides Structure N-linked oligosaccharides The carbohydrate moiety is attached at its anomeric carbon through glycosidic link to the amide group of the Asparagine side chain N-linked oligosaccharides fall into two classes: complex oligosaccharides and high mannose oligosaccharides Blood Group substances Blood group antigens are an important group of polysaccharide that attached as O-linked glycans to membrane proteins in some cell, or can be linked to a lipid molecule to form a glycolipid. These oligosaccharides that determine the blood group types (ABO) *all humans can produce can produce type O-oligosaccharides Addition of N-acetlygalactosamine by glycosyltransferase produces type A antigenÎ blood type A Addition of Galactose by the enzyme galactosyltransferase makes type B antigen Î blood type B * Humans possess no enzymes Î blood Type O * With the two enzymes Î blood type AB, both A and B oligosaccharides are present on the cell surface Transfusion relation ships between blood types Humans can produce antibody against A, B antigen, but type Opolysaccharides are non antigenic. •No one produce antibody against his own antigen but produces them against the other antigen. •Transfusion relation ships between blood types -type O is universal donor -type AB universal acceptor The End