Heteropolysaccharides: Structure and Function PDF

Heteropolysaccharides: Structure and Function Dr. Burak DURMAZ [email protected] Near East University, Faculty of Medicine, Department of Medical Biochemistry Prepared by Professor İzzet Hamdi ÖĞÜŞ Disaccharides Disaccharides consist of two monosaccharides jo...

Heteropolysaccharides: Structure and Function Dr. Burak DURMAZ [email protected] Near East University, Faculty of Medicine, Department of Medical Biochemistry Prepared by Professor İzzet Hamdi ÖĞÜŞ Disaccharides Disaccharides consist of two monosaccharides joined covalently by an O-glycosidic bond, which is formed when a hydroxyl group of one sugar reacts with the anomeric carbon of the other. This reaction represents the formation of an acetal from a hemiacetal (such as glucopyranose) and an alcohol (a hydroxyl group of the second sugar molecule). Glycosidic bonds are readily hydrolyzed by acid but resist cleavage by base. Thus disaccharides can be hydrolyzed to yield their free monosaccharide components by boiling with dilute acid. N-glycosylbonds join the anomeric carbon of a sugar to a nitrogen atom in glycoproteins and nucleotides. Disaccharides Disaccharides  POLYSACCHARIDES Homopolysaccharides contain only a single type of monomer; Heteropolysaccharides contain two or more different kinds.  FUNCTIONS OF POLYSACCHARIDES Some homopolysaccharides serve as storage forms of monosaccharides that are used as fuels; starch and glycogen are homopolysaccharides of this type. Homopolysaccharides like cellulose and chitin, for example serve as structural elements in plant cell walls and animal exoskeletons. Heteropolysaccharides provide extracellular support for organisms of all kingdoms. For example, the rigid layer of the bacterial cell envelope (the peptidoglycan) is composed in part of a heteropolysaccharide built from two alternating mono- saccharide units. In animal tissues, the extracellular space is occupied by several types of heteropolysaccharides, which form a matrix that holds individual cells together and provides protection, shape, and support to cells, tissues, and organs.  Starch Starch contains two types of glucose polymer, amylose and amylopectin. The amylose consists of long, unbranched chains of D-glucose residues connected by (a1-4) linkages. Such chains vary in molecular weight from a few thousand to more than a million. Amylopectin also has a high molecular weight (up to 100 million) but unlike amylose is highly branched. The glycosidic linkages joining successive glucose residues in amylopectin chains are (a 1-4); the branch points (occurring every 24 to 30 residues) are (a 1-6) linkages.  Glycogen Glycogen is the main storage polysaccharide of animal cells. Like amylopectin, glycogen is a polymer of (a1-4)-linked subunits of glucose, with (a1-6)-linked branches, but glycogen is more extensively branched (on average, every 8 to 12 residues) and more compact than starch. Glycogen is especially abundant in the liver, where it may constitute as much as 7% of the wet weight; it is also present in skeletal muscle. In hepatocytes glycogen is found in large granules Glycogen Glycogen Glycogen  Cellulose Cellulose, a fibrous, tough, water- insoluble substance, is found in the cell walls of plants, particularly in stalks, stems, trunks, and all the woody portions of the plant body. Cellulose constitutes much of the mass of wood, and cotton is almost pure cellulose. (b1-4) glycosidic bonds Like amylose, the cellulose molecule is a linear, unbranched homopolysaccharide, consisting of 10,000 to 15,000 D-glucose units. But there is a very important difference: in cellulose the glucose residues have the b-configuration), whereas in amylose, amylopectin, and glycogen the glucose is in the a-configuration. Cellulose Starch Glycogen  Chitin Chitin is a linear homopolysaccharide like cellulose, but composed of N-acetylglucosamine residues in (b1-4) linkage. The only chemical difference from cellulose is the replacement of the hydroxyl group at C- 2 with an acetylated amino group. Chitin forms extended fibers similar to those of cellulose, and like cellulose cannot be digested by vertebrates. Chitin is the principal component of the hard exoskeletons of nearly a million species of arthropods—insects, lobsters, and crabs, for example— and is probably the second most abundant polysaccharide, next to cellulose, in nature.  Dextrans Dextrans are bacterial and yeast polysaccharides made up of (a1- 6)-linked poly-D-glucose; all have (a1-3) branches, and some also have (a1-2) or (a1-4) branches. Dental plaque, formed by bacteria growing on the surface of teeth, is rich in dextrans. Synthetic dextrans are used in several commercial products (for example, Sephadex) that serve in the fractionation of proteins by size-exclusion chromatography. The dextrans in these products are chemically cross-linked to form insoluble materials of various porosities, admitting macromolecules of various sizes.  Folding of Homopolysaccharides Polysaccharides form three-dimensional macromolecular structures that are stabilized by weak interactions within or between molecules: hydrogen bond, hydrophobic, and van der Waals interactions, and, for polymers with charged subunits, electrostatic interactions. The most stable three-dimensional structure for starch and glycogen is a tightly coiled helix, stabilized by interchain hydrogen bonds. For amylose, the core of the helix is of precisely the right dimensions to accommodate iodine and this interaction with iodine is a common qualitative test for amylose (Iodine solution gives an intense blue color with starch).  Agarose Certain marine red algae, including some of the seaweeds, have cell walls that contain agar, a mixture of sulfated heteropolysaccharides made up of D-galactose and an L-galactose derivative ether-linked between C-3 and C-6. The two major components of agar are the unbranched polymer agarose (Mr ~120,000) and a branched component, agaropectin. The remarkable gel-forming property of agarose makes it useful in the biochemistry laboratory.  Glycosaminoglycans The extracellular space in the tissues of multicellular animals is filled with a gel-like material, the extracellular matrix (ECM), which holds the cells together and provides a porous pathway for the diffusion of nutrients and oxygen to individual cells. The extracellular matrix is composed of an interlocking meshwork of heteropolysaccharides and fibrous proteins such as collagen, elastin, fibronectin, and laminin.  Glycosaminoglycans Glycosaminoglycans, are a family of linear polymers composed of repeating disaccharide units. One of the two monosaccharides is always either N- acetylglucosamine or N-acetylgalactosamine; the other is in most cases a uronic acid, usually D- glucuronic or L-iduronic acid. In some glycosaminoglycans, one or more of the hydroxyls of the amino sugar are esterified with sulfate. Glycosaminoglycans are attached to extracellular proteins to form proteoglycans. Glycosaminoglycan Repeating disaccharide Hyaluronate Number of disaccharides per chain ~ 50 000 Hyaluronic acid (hyaluronate at physiological pH) contains alternating residues of D-glucuronic acid and N-acetylglucosamine, with up to 50,000 repeats of the basic disaccharide unit, hyaluronates have molecular weights greater than 1 million; they form clear, highly viscous solutions that serve as lubricants in the synovial fluid of joints. Hyaluronate is also an essential component of the extracellular matrix of cartilage and tendons, to which it contributes strength and elasticity as a result of its strong interactions with other components of the matrix.  Glycosaminoglycans Hyaluronidase, an enzyme secreted by some pathogenic bacteria, can hydrolyze the glycosidic linkages of hyaluronate, rendering tissues more susceptible to bacterial invasion. In many organisms, a similar enzyme in sperm hydrolyzes an outer glycosaminoglycan coat around the ovum, allowing sperm penetration.  Glycosaminoglycans Glycosaminoglycan Repeating disaccharide Chondroitin 4- sulfate Number of disaccharides per chain 20 - 60 Other glycosaminoglycans differ from hyaluronate in two respects: 1. They are generally much shorter polymers and 2. They are covalently linked to specific proteins (proteoglycans). Chondroitin sulfate contributes to the tensile strength of cartilage, tendons, ligaments, and the walls of the aorta.  Glycosaminoglycans Glycosaminoglycan Repeating disaccharide Keratan sulfate Number of disaccharides per chain ~ 25 Dermatan sulfate contributes to the pliability of skin and is also present in blood vessels and heart valves. In this polymer, many of the glucuronate (GlcA) residues present in chondroitin sulfate are replaced by their epimer, iduronate (IdoA). Keratan sulfates have no uronic acid and their sulfate content is variable. They are present in cornea, cartilage, bone, and a variety of horny structures formed of dead cells: horn, hair, hoofs, nails, and claws.  Glycosaminoglycans Glycosaminoglycan Repeating disaccharide Heparin Number of disaccharides per chain 15 – 90 Heparin is a natural anticoagulant made in mast cells (a type of leukocyte) and released into the blood, where it inhibits blood coagulation by binding to the protein antithrombin. Heparin binding causes antithrombin to bind to and inhibit thrombin, a protease essential to blood clotting. The interaction is strongly electrostatic; heparin has the highest negative charge density of any known biological macromolecule. Purified heparin is routinely added to blood samples obtained for clinical analysis, and to blood donated for transfusion, to prevent clotting.  GLYCOCONJUGATES Proteoglycans, Glycoproteins, and Glycolipids In addition to their important roles as stored fuels (starch, glycogen, dextran) and as structural materials (cellulose, chitin, peptidoglycans), polysaccharides and oligosaccharides are information carriers: they serve as destination labels for some proteins and as mediators of specific cell-cell interactions and interactions between cells and the extracellular matrix. Specific carbohydrate containing molecules act in cell-cell recognition and adhesion, cell migration during development, blood clotting, the immune response, and wound healing. In most of these cases, the informational carbohydrate is covalently joined to a protein or a lipid to form a glycoconjugate, which is the biologically active molecule. Bacterial Cell Wall : Peptidoglycan  Bacterial Cell Wall : Peptidoglycan The rigid component of bacterial cell walls is a heteropolymer of alternating (b1-4)-linked N-acetylglucosamine and N-acetylmuramic acid residues. The linear polymers lie side by side in the cell wall, crosslinked by short peptides, the exact structure of which depends on the bacterial species. The peptide cross-links weld the polysaccharide chains into a strong sheath that envelops the entire cell and prevents cellular swelling and lysis due to the osmotic entry of water. The enzyme lysozyme kills bacteria by hydrolyzing the (b1-4) glycosidic bond between N-acetylglucosamine and N-acetylmuramic acid. Lysozyme is notably present in tears, presumably as a defense against bacterial infections of the eye. Penicillin and related antibiotics kill bacteria by preventing synthesis of the cross-links, leaving the cell wall too weak to resist osmotic lysis. PROTEOGLYCAN – an ECM Macromolecule Proteoglycans are macromolecules of the cell surface or extracellular matrix (ECM) in which one or more glycosaminoglycan chains are joined covalently to a membrane protein or a secreted protein. Proteoglycans are major components of connective tissue such as cartilage, in which their many noncovalent interactions with other proteoglycans, proteins, and glycosaminoglycans provide strength and resilience. PROTEOGLYCAN – an ECM Macromolecule  PROTEOGLYCAN – an ECM Macromolecule Some proteoglycans can form proteoglycan aggregates, enormous supramolecular assemblies of many core proteins all bound to single molecule of hyaluronan. Interactions between cells and extracellular matrix  Glycoproteins Glycoproteins are carbohydrate-protein conjugates in which the glycans are smaller, branched, and more structurally diverse than the glycosaminoglycans of proteoglycans. They are found on the outer face of the plasma membrane, in the extracellular matrix, and in the blood. Inside cells they are found in specific organelles such as Golgi complexes, secretory granules, and lysosomes. The oligosaccharide portions of glycoproteins are less complex than the glycosaminoglycan chains of proteoglycans. Glycoproteins are rich in information, forming highly specific sites for recognition and high-affinity binding by other proteins. Oligosaccharide linkages in glycoproteins Bacterial lipopolysaccharides Glycolipids are membrane lipids in which the hydrophilic head groups are oligosaccharides. As in glycoproteins, they act as specific sites for recognition by carbohydrate- binding proteins.  Glycolipids Glycolipids are involved in intercellular communication. Oligosaccharides of identical composition are present in both the glycolipids and glycoproteins associated with the cell membrane, where they serve as cell recognition factors. For example, carbohydrate residues in these oligosaccharides are the antigens of the ABO blood group substances  Carbohydrate-Protein Interaction Lectins, found in all organisms, are proteins that bind carbohydrates with high affinity and specificity. Lectins serve in a wide variety of cell-cell recognition, signaling, and adhesion processes and in intracellular targeting of newly synthesized proteins. The adhesion of bacterial and viral pathogens to their animal-cell targets occurs through binding of lectins in the pathogens to oligosaccharides in the target cell surface. Selectins are plasma membrane lectins that bind carbohydrate chains in the extracellular matrix or on the surfaces of other cells, thereby mediating the flow of information between cell and matrix or between cells. Role of lectin-ligand interactions in lymphocyte movement to the site of an infection or injury. Roles of oligosaccharides in recognition and adhesion at the cell surface