Carbohydrates Polysaccharides Polymers of Disaccharides

Carbohydrates A. Definition B. Roles C. Monosaccharides 1. Chirality a. One or more asymmetric carbons b. Linear and ring forms 2. Derivatives: the chemistry of carbohydrates 3. Polymerization a. The Glycosidic Bond D. Oligosaccharides 1. 2. 3. 4. Glycoproteins & glycolipids O-linked N-linked Sequence determination-ABO E. Polysaccharides 1. Polymers of glucose 2. Polymers of disaccharides Vitamins & Cofactors A. B. Water soluble Fat Soluble Metabolism Carbohydrates Polysaccharides: Polymers of Disaccharides Extracellular Matrix (ECM) • Main components – proteoglycans – collagen & elastin fibers • Proteoglycans – Different glycosaminoglycans are O-linked to the “core protein.” • ECM is a barrier for tumor cells seeking to invade new tissues. – Some tumor cells secrete heparinase that degrades ECM. • Cosmetics 1 Carbohydrates Polysaccharides: Polymers of Disaccharides Glycosaminoglycans Carbohydrates Polysaccharides: Polymers of Disaccharides Glycosaminoglycans 2 Linkages all b(1à3) Linkages all b(1à4) (COO–) GlcUA – GalNAc GlcUA – GlcNAc L-IdoUA (C5 epimer C4sulfate only C6/C4-sulfate of D-Glc) & – (SugarX – SugarY)n – Linkages all b(1à4) GlcUA(IdoUA) or Gal GlcNAc or GalNAc or GlcN b(1à3) a(1à4) (COO–) GlcUA – GlcN Gal – L-IdoUA GlcNAc Sulfate everywhere, including GlcN GlcNAc C6-sulfate Glycosaminoglycans – (SugarX – SugarY)n – GlcUA(IdoUA) or Gal GlcNAc or GalNAc or GlcN GlcUA – GlcNAc GlcUA GlcUA – GalNAc (C6/C4-sulfate) Gal – GlcNAc C6-sulfate Linkages all b, and opposite of Hyl & CS alternate (1à4) & (1à3) GlcUA GlcUA or IdoUA – GlcN Sulfate everywhere, including GlcN Linkages all (1à4), alternate a & b IdoUA 3 Hyl & Aggrecan Carbohydrates Polysaccharides: Proteoglycans = Polymers of Disaccharides (glycosaminoglycans) + proteins a.k.a. - mucopolysaccharides Aggrecan 4 Carbohydrates Polysaccharides: Proteoglycans = Polymers of Disaccharides (glycosaminoglycans) + proteins a.k.a. - mucopolysaccharides Sulfated glycosaminoglycans attached to a large rod-shaped protein in cell membrane • syndecans: protein has a single transmembrane domain • glypicans: protein is anchored to a lipid membrane Interact with a variety of receptors from neighboring cells and regulate cell growth Carbohydrates Polysaccharides: Proteoglycans = Polymers of Disaccharides (glycosaminoglycans) + proteins a.k.a. - mucopolysaccharides • Some integral membrane proteins are proteoglycans. • Other integral membrane proteins are receptors for extracellular proteoglycans. • These proteins link cellular cytoskeleton to the ECM and transmit signals into the cell to regulate: – – – – – – • Integrins (which then interact with Actin) cell growth cell mobility apoptosis wound healing In chondrocytes, huge amounts of cartilage proteoglycans are produced (Aggrecan) – – – – • syndecans Resilience Plasticity Cushioning Due to reversible hydration Heparin is linear polymer, 3–40 kDa. – – – – – – – Heparan sulfate is heparin-like polysaccharide but attached to proteins. Highest density of negative-charge of any biomolecule Prevent blood clotting by activating protease inhibitor antithrombin III Binding to various cells regulates development and formation of blood vessels. Modulates growth and development by binding growth-factor receptors Important role in cancer metastasis Can also bind to viruses and bacteria and decrease their virulence 5 Carbohydrates Polysaccharides: Proteoglycans = Polymers of Disaccharides (glycosaminoglycans) + proteins a.k.a. - mucopolysaccharides Heparin Prevent blood clotting by activating protease inhibitor antithrombin III TABLE 7-2 Structures and Roles of Some Polysaccharides Size (number of monosaccharide units) Typea Repeating unitb Amylose Amylopectin HomoHomo- (α1èS4) Glc, linear (α1èS4) Glc, with (α1èS6) Glc branches every 24–30 residues 50–5,000 Up to 106 Glycogen Homo- (α1èS4) Glc, with (α1èS6) Glc branches every 8–12 residues Up to 50,000 Energy storage: in bacteria and animal cells Cellulose Homo- (β1èS4) Glc Up to 15,000 Structural: in plants, gives rigidity and strength to cell walls Chitin Homo- (β1èS4) GlcNAc Very large Structural: in insects, spiders, crustaceans, gives rigidity and strength to exoskeletons Dextran Homo- (α1èS6) Glc, with (α1èS3) branches Wide range Structural: in bacteria, extracellular adhesive Peptidoglycan Hetero-; peptides attached 4)Mur2Ac(β1èS4) GlcNAc(β1 Very large Structural: in bacteria, gives rigidity and strength to cell envelope Agarose Hetero- 3)D-Gal (β1èS4)3,6- anhydroL-Gal(α1 1,000 Structural: in algae, cell wall material Hyaluronan (a glycosaminoglycan) Hetero-; acidic 4)GlcA (β1èS3) GlcNAc(β1 Up to 100,000 Structural: in vertebrates, extracellular matrix of skin and connective tissue; viscosity and lubrication in joints Primer Starch Roles/significance Energy storage: in plants Starch a Each polymer is classified as a homopolysaccharide (homo-) or heteropolysaccharide (hetero-). b The abbreviated names for the peptidoglycan, agarose, and hyaluronan repeating units indicate that the polymer contains repeats of this disaccharide unit. For example, in peptidoglycan, the GlcNAc of one disaccharide unit is (β1èS4)-linked to the first residue of the next disaccharide unit. 6