Carbohydrates Polysaccharides Dr. Nikhat Siddiqi

Contents Polysaccharides – Classification Homoglycans Heteroglycans Dr. Nikhat Siddiqi

Joining of monosaccharides Monosaccharides can be joined to form disaccharides, oligosaccharides, and polysaccharides. Important disaccharides include lactose (galactose + glucose), sucrose (glucose + fructose), and maltose (glucose + glucose). Important polysaccharides include branched glycogen (from animal sources) and starch (plant sources) and unbranched cellulose (plant sources); each is a polymer of glucose. The bonds that link sugars are called glycosidic bonds. These are formed by enzymes known as glycosyltransferases. Dr. Nikhat Siddiqi

Naming glycosidic bonds Glycosidic bonds between sugars are named according to the numbers of the connected carbons, and also with regard to the position of the anomeric hydroxyl group of the sugar involved in the bond. Dr. Nikhat Siddiqi

Naming glycosidic bonds If this anomeric hydroxyl is in the α configuration, the linkage is an α-bond. If it is in the β configuration, the linkage is a β-bond. Lactose, for example, is synthesized by forming a glycosidic bond between carbon 1 of β-galactose and carbon 4 of glucose. The linkage is, therefore, a β(1→4) glycosidic bond. Dr. Nikhat Siddiqi

Polysaccharides Polysaccharides are also called as glycans. Made up of large number of monosaccharides linked by glycosidic linkages. Smaller glycans are called as oligosaccharides (10-15 monomers) found attached to popypeptides in glycoproteins and some glycolipids. Found in membrane and secretary proteins. Dr. Nikhat Siddiqi

Polysaccharides - Classification Homoglycans Polysaccharides Heteroglycans Dr. Nikhat Siddiqi

Polysaccharides - Classification Structural Polysaccharides Polysaccharides Storage Polysaccharides Dr. Nikhat Siddiqi

Homoglycans Found in starch, glycogen, cellulose and chitin. Starch, glycogen, cellulose give D-glucose when hydrolysed. Starch –energy storage molecule in plants. Glycogen –energy storage molecule in animals. Chitin – component of exoskeleton of insects, cell wall of fungi, yields glucose derivative N-acetylglucosamine when hydrolyzed. Dr. Nikhat Siddiqi

Starch (Storage Polysacchardes) Significant source of carbohydrate in human diet. Source- potatoes, rice, wheat, corn. Amylose Starch Amylopetin Dr. Nikhat Siddiqi

Amylose Composed of long, unbranched chains of S-glucose residues that are linked by (1,4) glycosidic bonds. Have one reducing end in which the ring can open to form free aldehyde group with reducing properties. Dr. Nikhat Siddiqi

Amylose Contains several thousand glucose residues has molecular weight 150,000 to 600,000. Linear amylose molecule forms tight helices. Gives blue colour with iodine due to interaction between iodine molecules and the helically arranged glucose rsidues. Dr. Nikhat Siddiqi

Amylopectin is branched polymer containing (1,4) and (1,6)glycosidic linkages. The (1,6) points may occur every 20 to 35 residues and prevent helix formation. Dr. Nikhat Siddiqi

Starch digestion begins in the mouth where the salivary enzyme - amylase initiates hydrolysis of glycosidic bonds. Digestion continues in the small intestine where pancreatic -amylase hydrolyzes all the (1,4) glycosidic bonds except the branch points. The products of - amylase maltose, trisaccharide maltotriose and  limit dextrin. Dr. Nikhat Siddiqi

Starch - Structure Dr. Nikhat Siddiqi

Glycogen (Storage Polysaccharides) Storage carbohydrate in vertebrates. Found in liver and skeletal muscle. Structure similar to amylopectin except that it has more branch point possibly at every fourth glucose residue. Dr. Nikhat Siddiqi

Glycogen-Structure Dr. Nikhat Siddiqi

Glycogen- Structure Dr. Nikhat Siddiqi

Cellulose (Structural Polysaccharides) Polymer of D-glucopyranose residues linked by (1,4) glycosidic bonds. Unbranched Structural polysaccharide in plants. Pairs of unbranched cellulose molecules may contain as many as 12,000 glucose units each held together by hydrogen bonding to form sheet like strips called microfibrils. These structures are found in primary and secondary cell walls of plants. Dr. Nikhat Siddiqi

Cellulose makes up dietary fiber. The ability to digest cellulose is found in microorganism which contain the enzyme cellulase. Cellulose can be hydrolyzed to its constituent glucose units by microorganisms that inhabit the digestive tract of termites and ruminants. Cellulose makes up dietary fiber. Paper, wood, textiles are some of cellulose containing products. Dr. Nikhat Siddiqi

Cellulose - Structure Dr. Nikhat Siddiqi

Chitin (Structural Polysaccharide) Chitin is an unbranched polymer of N-Acetyl-D-glucosamine. It is found in fungi and is the principal component of arthropod and lower animal exoskeletons, e.g., insect, crab, and shrimp shells. It may be regarded as a derivative of cellulose, in which the hydroxyl groups of the second carbon of each glucose unit have been replaced with acetamido (-NH(C=O)CH3) groups. Dr. Nikhat Siddiqi

Chitin - Structure Dr. Nikhat Siddiqi

Polysaccharides Heteroglycans Dr. Nikhat Siddiqi

Heteroglycans High molecular weight carbohydrate polymers that contain more than one kind of monosaccharides. Major classes found in animals are N and O-linked glycans attached to proteins. Dr. Nikhat Siddiqi

Glycosaminoglycans (GAGs) Glycosaminoglycans (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 over 95% carbohydrate. Dr. Nikhat Siddiqi

Glycosaminoglycans have 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, which, along with fibrous components such as collagen, make up the extracellular matrix. The viscous, lubricating properties of mucous secretions also result from the presence of glycosaminoglycans, which led to the original naming of these compounds as mucopolysaccharides. Dr. Nikhat Siddiqi

Structure of Glycosaminoglycans Glycosaminoglycans are long, unbranched, heteropolysaccharide chains generally composed of a repeating disaccharide unit [acidic sugar–amino sugar]n. Dr. Nikhat Siddiqi

Structure of Glycosaminoglycans The amino sugar is either D-glucosamine or D-galactosamine, in which the amino group is usually acetylated, thus eliminating its positive charge. The amino sugar may also be sulfated on carbon 4 or 6 or on a nonacetylated nitrogen. The acidic sugar is either D-glucuronic acid or its carbon-5 epimer, L-iduronic acid. Dr. Nikhat Siddiqi

Structure of Glycosaminoglycans A single exception is keratan sulfate, in which galactose rather than an acidic sugar is present. These acidic sugars contain carboxyl groups that are negatively charged at physiologic pH and, together with the sulfate groups, give glycosaminoglycans their strongly negative nature. Dr. Nikhat Siddiqi

Some monosaccharide units found in glycosaminoglycans. Dr. Nikhat Siddiqi

Functions of GAGs Because of their large number of negative charges, these heteropolysaccharide chains tend to be extended in solution. They repel each other, and are surrounded by a shell of water molecules. When brought together, they “slip” past each other, much as two magnets with the same polarity seem to slip past each other. This produces the “slippery” consistency of mucous secretions and synovial fluid. Dr. Nikhat Siddiqi

Functions of GAGs---cont When a solution of glycosaminoglycans is compressed, the water is “squeezed out” and the glycosaminoglycans are forced to occupy a smaller volume. When the compression is released, the glycosaminoglycans spring back to their original, hydrated volume because of the repulsion of their negative charges. This property contributes to the resilience of synovial fluid and the vitreous humor of the eye. Dr. Nikhat Siddiqi

Classification of the glycosaminoglycans The six major classes of glycosaminoglycans are divided according to monomeric composition, type of glycosidic linkages, and degree and location of sulfate units. Dr. Nikhat Siddiqi

Structure and distribution of glycosaminoglycans (GAGs). Dr. Nikhat Siddiqi

Hyaluronic Acid Hyaluronate molecules may consist of as many as 25,000 disaccharide units, with molecular weights of up to 107. Hyaluronates are important components of the vitreous humor in the eye and of synovial fluid, the lubricant fluid of joints in the body. Dr. Nikhat Siddiqi

The chondroitins and keratan sulfate are found in tendons, cartilage, and other connective tissue, whereas dermatan sulfate, as its name implies, is a component of the extracellular matrix of skin. Heparin, with the highest net negative charge of the disaccharides shown, is a natural anticoagulant substance. Dr. Nikhat Siddiqi

Mucopolysaccharidoses The mucopolysaccharidoses are hereditary disorders (1:25,000 births) that are clinically progressive. They are characterized by accumulation of glycosaminoglycans in various tissues, causing varied symptoms, such as skeletal and extracellular matrix deformities, and mental retardation. Mucopolysaccharidoses are caused by a deficiency of any one of the lysosomal hydrolases normally involved in the degradation of heparan sulfate and/or dermatan sulfate . Dr. Nikhat Siddiqi

Mucopolysaccharidoses MPS Type I Hurler’s syndrome results from a deficiency of alpha-L-iduronidase. Heparan sulfate and dermatan sulfate accumulate. There is growth and mental retardation with characteristic facial changes. MPS Type II Hunters syndrome is similar to Hurler’s syndrome but the enzyme deficiency is for iduronate sulfatase and the inheritance is X-linked. Dr. Nikhat Siddiqi

Glycoconjugates Compounds which result from the covalent linkages of carbohydrate molecules to both proteins and lipids. Two classes A) proteoglycans B) glycoproteins Glycolipids are oligosaccharides containing lipid molecules found mainly on the outer surface of plasma membranes. Dr. Nikhat Siddiqi

Polysaccharides Two broad classed viz., N-linked and O-linked. N-linked are attached to polypeptides by an N-glycosidic bond with the side chain amide group of amino acid asparagine. O-linked are attached to polypeptides by side chain hydroxyl group of the amino acid serine or threonine in a polypeptide chain or the hydroxyl group of membrane lipids. Dr. Nikhat Siddiqi

Polysaccharides linked to polypeptides Dr. Nikhat Siddiqi

Proteoglycans High carbohydrate content (about 95%). Occur on cell surfaces or are secreted into extracellular matrix. Dr. Nikhat Siddiqi

Proteoglycans Proteoglycans consist of a protein core (brown) and one or more covalently attached glycosaminoglycan chains ([blue]. Dr. Nikhat Siddiqi

Examples include syndecans, glycipcans and affrecans The syndecans are a class of heparan sulfate and chondroitin sulfate containing proteoglycans in which the core protein is a transmembrane protein. Aggregans is found in cartilage. Dr. Nikhat Siddiqi

Proteoglycan Proteoglycan monomers typically are bound non-covalently to a hyaluronic acid molecule in association with linker proteins in a “bottle brush” arrangement. Dr. Nikhat Siddiqi

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Functions of Proteoglcans Organizing extracellular matrix. Membrane bound syndecans, glycipcans bind to specific signal molecules like growth factors involved in cell cycle regulation. Because of their vast number of polyionic GAG chains, the aggrecans trap large volume of water. Give strength, flexibility to cartilage and tensile strength to collagen fibers. Dr. Nikhat Siddiqi

Glycoproteins Proteins that are linked covalantly to carbohydrates through N- or 0- linkages. Carbohydrate content varies from 1% to more than 85% of total weight. Carbohydrates include monosaccharides or disaccharides such as those attached to collagen or branched oligosaccharides found on plasma glycoproteins. Dr. Nikhat Siddiqi

Polysaccharides linked to polypeptides Dr. Nikhat Siddiqi

Differences between Glycoproteins and Protoglycans They differ from the proteoglycans (which might be considered a special case of glycoproteins) in that the length of the glycoprotein's carbohydrate chain is relatively short (usually 2–10 sugar residues in length, although they can be longer). Dr. Nikhat Siddiqi

Differences between Glycoproteins and Protoglycans ---cont In addition, whereas glycosaminoglycans have diglucosyl repeat units, the carbohydrates of glycoproteins do not have serial repeats. The glycoprotein carbohydrate chains are often branched instead of linear, and may or may not be negatively charged. Dr. Nikhat Siddiqi

Glycoproteins contain highly variable amounts of carbohydrate. For example, immunoglobulin IgG, contains less than 4% of its mass as carbohydrate, whereas human gastric glycoprotein (mucin) contains more than 80% carbohydrate. Dr. Nikhat Siddiqi

Functions of glycoproteins Membrane-bound glycoproteins participate in a broad range of cellular phenomena, including cell surface recognition (by other cells, hormones (insulin receptors), and viruses), cell surface antigenicity (such as the blood group antigens), as components of the extracellular matrix and of the mucins of the gastrointestinal and urogenital tracts, where they act as protective biologic lubricants. Dr. Nikhat Siddiqi

Functions of Glycoproteins Dr. Nikhat Siddiqi

Sialic acid residues are responsible for high viscosity and luricating properties of saliva. Cellular adhesion eg selectins (transient cell-cell interaction), intergins (cell attachment to components of extracellular matrix) and cadherins (calcium dependent binding of cells to each other within tissue. Dr. Nikhat Siddiqi

Dr. Nikhat Siddiqi