Today s lecture Carbohydrates goals of the course review of the syllabus and general lecture format BCMB 8020 recommended and required reading material April 7 2009 chemical background of sugars and polysaccharides Dr Lianchun Wang oligosaccharide diversity Email lwang ccrc uga edu key concepts in oligosaccharide biosynthesis 1 Goals of the course 2 General lecture format understand the biochemistry of sugars and oligosaccharides glycan type biological system learn the approaches used to analyze carbohydrate content and structure 1 2 3 4 appreciate the structural diversity of oligosaccharides in different biological systems structure biosynthesis function research frontiers Required and recommended reading material understand the function of oligosaccharides in different organisms Voet and Voet 3rd edition Chapter 8 appreciate the current research frontiers in areas of glycobiology and the biomedical relevance of oligosaccharides Essentials of Glycobiology 2nd Edition Chapters 2 8 9 15 16 20 21 39 47 available online at PubMed under Books Review and journal articles 3 4 Carbohydrate saccharide sugar CH2O 6 most abundant biological molecule Chemical simple C H O CH2O n Basic unit monosaccharide Monosaccharide covalently link together The Chemistry and Biochemistry of Sugars to form polysaccharide Structurally more heterogenous than protein and nucleic acids size composition Biological functions Multiple energy source structural materials mediate many key recognition events between proteins and cells 5 6 Monosaccharides are aldoses or ketoses Monosaccharides are aldoses or ketoses aldoses aldose ketose Fischer projections 7 8 D sugar vs L sugar O C H HO C H ketoses H C OH HO C H HO C H CH2OH L Glucose 9 all D sugars have the same absolute configuration at the asymmetric center farthest removed from their carbonyl group According to the Fischer convention D sugars are the mirror images of L sugars 10 Epimers The sugars that differ only by the configuration around one C atom D glucose and D mannose are epimers 11 12 Cyclic sugars Hydroxyl groups and either the aldehyde or ketone groups of monosaccharides can react intramolecularly to form cyclic sugars Haworth projections are convenient formulas to represent the configuration of sugar substituents 13 Sugars with a 6 and 5 membered ring are known as pyranose and furanose respectively internal strain of 3 and 4 membered rings makes them less stable than the linear strains 15 14 Cyclic sugars have two anomeric forms and the cyclization of a monosaccharide renders the carbonyl carbon asymmetric in solution D glucose is a mixture of the anomer 63 6 and the anomer 36 4 linear form is present in very small amounts the pure anomers have unique chemical properties i e optical rotation 16 Sugars can adopt different conformations overall conformation of sugars is not planar carbon centers have an sp3 hybridization Conformation e g chair or boat shifts readily since no bonds are broken Configuration e g and anomers shift between anomers is slow in solution since bonds are broken and re formed Epimerization e g C2 epimers glucose vs mannose does not occur without appropriate enzyme substituents can be either axial or equatorial D glucose is the only sugar that can have all 5 of its non H substituents in the equatorial position the equatorial position of OH or CH2OH substituents is more sterically favored 17 Sugars are often modified 18 Glycosidic bonds Oxidation 1 aldehyde gloup carboxylic acid group aldonic acid e g gluconic acid 2 primary alcohol group carboxylic acid group uronic acid e g glucuronic acid Reduction carbonyl group polyhydroxy acohols alditol e g glycerol the bond that links two monosaccharides technically it is the bond connecting the anomeric carbon to the other molecules Canomeric OR glycosidic bond Deoxygenation of hydroxyl group Replace hydroxyl group by H e g D 2 deoxyribose DNA Amino sugars Replace hydroxyl group by amino group e g D glucosamine D galactosamine Methylation of hydroxyl group occurs in nature and also an approach for structural analysis Esterification of hydroxyl group phosphate sulfate19 20 There are basically 2 things we need to keep track of 1 the anomeric configuration of the glycosidic linkage 2 the identity of the carbon on the next sugar that shares the bridging oxygen naming begins with the sugar farthest from the reducing terminus of the oligosaccharide the reducing sugar is the sugar that still contains a free anomeric carbon O D galactopyranosyl 1 4 D Glucopyranose 21 22 N glycosidic bonds link the anomeric carbon and an amine occurring the link between the sugars and bases of DNA and RNA Examples of glycosidic bonds 23 24 How are glycosidic linkages and oligosaccharides represented Glycosidic bonds are shortened to convey only the position of the anomeric carbon and the carbon of the next sugar in the structure Glucose 1 4 Galactose Glc 4Gal symbols are used to represent sugars instead of Haworth projections or chair diagrams Fuc 3 Sia 3Gal 4GlcNAc 2Man Simplified Traditional Fuc 6 6 Man 4GlcNAc 4GlcNAc 3 9Ac Sia 6Gal 4GlcNAc 2Man 25 Symbolic Representati on 3 9Ac 6 4 3 4 3 2 2 6 3 4 3 6 4 9Ac 4 2 6 3 3 4 4 4 6 9Ac 2 26 Common classes of animal glycans The diversity of oligosaccharides is enormous and gives these structures the capacity to mediate many important biological functions the diversity of oligosaccharide structures stems from properties inherent to sugars themselves multiple monosaccharides several configurations many derivatives multiple possible linkages branching Essentials of Glycobiology Second Edition 27 Chapter 1 Figure 6 28 The Complexity of Carbohydrates H H H 6 OH H H 22O Cn6 H O O n6 H C6H12O6 4 H 66 OH H 5 H 44 HO OH H HO O O H OH H 22 3 H Ala CH3 OH H2N O OH H 2 H H O H OH Gly H OH OH OH H O OH OH OH H NH Ala H2N H Gly OH H O OH H H OH H H OH D Galacturonic acid GalA GalA 29 CH3 H O D Glucosamine GlcN GlcN H H H NH2 O H O OH H H OH H H HO H D Galactose Gal H O OH H D Mannose Man 1 OH OH H OH H OH H H2N H2N 3 H H OH H O OH HO D Glucose Glc Glc 11 H H 6 OH 6 H 5 O OH OH H 1 4 OH H 2 3 H H O H H OH Gly NH H 30 The Complexity of a Disaccharide The Complexity of a Dipeptide O OH H Glc D Glucose Glc H 5 OH H OH H Gal Gal 1 Gal 1 3 Glc Ala Gal 1 Gal 1 4 Glc 4 HO OH 3 5 H O OH H 2 1 H OH Glc 1 Glc 1 1 Gal Glc 1 Glc 1 2 Gal Gal 1 Gal 1 6 Glc 31 H 6 OH Glc Gal 1 Gal 1 2 Glc CH3 OH H H OH Gal 1 Gal 1 1 Glc O H Glc 1 Glc 1 3 Gal Glc 1 Glc 1 4 Gal Glc 1 Glc 1 6 Gal 36 32 How is the