Ch. 9 - Carbohydrates & Glycobiology. 3 major size classes. Carbon atoms attached to -OH groups often chiral centers. Monosaccharides & Disaccharides

Transcription

1 Ch. 9 - Carbohydrates & Glycobiology Mono- and disaccharid es (simple su gar s) Oligosacc har ides (inf orm ationa l molecu les) Polysaccharides (ergy stores, cell structures) Glycoconjuga tes Proteoglycans Glycoproteins Glycolipids & lipopolysaccharides Lectins 3 major size classes Monosacc har ides Single units Oligosacc har ides 2-20 monosaccharide units Polysaccharides > 20 monosaccharid e units Carbohydrate-binding proteins 1 2 Monosaccharides & Disaccharides O Aldehydes CH 3 CH 2 CH 2 C H Carbon atoms attached to -OH groups often chiral centers Ketones O CH 3 CH 2 CH 2 C CH 3 Each with mu ltiple hydroxyl (-O H) groups Fig Some nomenclature Most monosaccharides have 3-7 carbons Fig 9.1 Fig 9.1 Aldose - monosa ccharide derivative of aldehyde Ketose - monosaccharide deriva tive of ketone 5 3C = triose 4C = tetrose 5C = pentose 6C = hexose 7C = heptose, etc. 6 1

2 Stereoisomerism D- or L- configuration? HO H L Fig 9.2 Glycer aldehyde is re ference molec ule for defining D- or L- stereoisomer s 7 Use carbon most distant from carbonyl carbon 8 Molecules with n chiral centers have 2 n stereoisomers Epimers = monosaccharides which differ in configuration around a single carbon Fig 9.4 Fig Monosaccharides have cyclic structures 6-member ring compounds = pyranoses Fig 9.7 Fig member ring compounds = furnanoses 12 2

3 Hexose derivatives Disaccharides & glycosidic bonds Fig Fig Glycosidic bond for mation Polysaccha rides Fig Fig 9.13 Identity of monosaccharide units Length of chains Degree of bra nching Types of glycosidic bonds (α1-4) (β1-4) (α1-6) e tc. 16 Starch - plant carb storage Combination of (α1-4) and (α1-6) linkages Fig 9.15 Fig

4 Branching speeds utilization of glucose Storing glucose as polymers makes colligative sense Polyme rs reduce difference in osmotic pressure b/w interior & exterior of ce ll Fig 9.15 Fig Polysaccharides: Cellulose 3D structure: Starch vs. Cellulose cellulose Fig 9.17 Fig 9.17 Cellulose Fig 9.16 Starch 21 Result of α vs β glycosidic bonds 22 Chitin - hard exoskeletons Polysaccharide-petide linkages - peptidoglycans Fig 9.18 (β1-4) glycosidic linkages 23 Fig 9.19 Alternating (β1-4) linked N-acetylgluc osamine & N-acetylmuramic acid 24 4

5 Polysaccha rides - Glycosaminoglycans Diverse roles for polysaccharides Fig 9.20 Polyme rs of alternating uronic acid and amino su gars Glycoconjugates Car bohydrates covale ntly linked to peptide s, proteins or lipids Proteoglycans Figs 9.22,23 Variety of physiological roles Cell-Cell recogni tion, adhesio n or migration Blood clotting Immune response Wound healing Multiple sites for H- or Electrostatic bonding 27 core proteins c ovalently linke d to glycosaminoglycans 28 Glycoproteins Carbohydrate portions smaller, more structurally diverse than glycosaminoglycans Biological advantages of glycosylation Hydrophilic clusters of -OH, SO 4 -, COO -, etc. Influence on protein structure and/or fold ing Possible Protec tion from proteolytic degrad ation Structural/charge barrier to proteases Fig 9.25 Car bohydrate a ttached via glycosidic link to Ser, Structural diver sity of oligosaccharide labels Protein destination Hormone/protein receptors Cell and protein age indicators Thr or Asn residues

6 Oligosaccharide diversity Glycolipids & lipopolysaccharides Fig 9.25 Monosacc har ides Glycosidic linkages (α,β, 1-4, 2-3, etc.) glycoforms - same protein, different oligosac c s 31 Fig 9.26 Lipids covalently bound to complex oligosacc cha ins 32 Glycoconjugates & the extracellular matrix Lectins - proteins that bind ca rbohydrates with high affinity & specificity Identification of old proteins Vectoring immune cells to sites of infection Means of infection or a ttachment by microbial pathogens H. pylori (gastric ulcers) Cholera toxin Whoopin g cough Fig 9.24 Cell-cell ad hesion & communic ation 33 Influenza virus 34 Oligosaccharides in adhesion and recognition Carbohydrates - summary Cycliz ed, polyhydroxy ald ehydes or ketones Monosaccharid es lectins Oligosaccharid es Polysaccharides Monosacc har ides have > 1 asymmetric carbon Exist in stereoisom eric forms (D- or L-) Multiple chiral centers is the norm Fig 9.29 Furanoses = 5-membered rin gs Pyranoses = 6-membered rin gs

7 Furanoses & pyranoses occur in anomeric α and β forms - differences in c onfiguration about hemiacetal or hemiketa l c arbon Ma ny hexoses d erivatized by ad ding amino, ace tyl or sulfate grou ps Oligo- and polysacc har ides consist of monosacc har ides joined by glyc osidic bonds (α1-4), (β1-4) etc. 37 Oligo- and polysacc har ide dive rsity: Composition (mono s) Molecular weight (no. mono s) Glycosid ic linkages Degree of branching Oligo- and polysacc har ide roles: ergy storage Structural (cellulose, chitin, glycosaminoglycans ) Information (labels) Protein structure & stability (folding, protease protection) 38 Glycoconjuga tes: Proteoglycans glycoproteins glycolipids/lipopolysaccharides Glycolipids/lipid polysac cha rides Outer surface of cell m embranes Cell labels Recognit ion sites for prot ein binding Proteoglyc ans More glycan than protein Lectins Glycosamin oglycan-prot eins of extracellular matrix Carbohydrate-binding proteins Cell-cell adhesion Mediate cell-cell i nteractions Pathogens Immune system, etc. Glycoproteins More protein than glycan Structurall y diverse o ligos Secreted proteins, labels, cell surface interactions