Carbohydrates - By Henry Wormser - PhD Professor Of Medicinal Chemistry

Carbohydrates By Henry Wormser, Ph.D Professor of Medicinal Chemistry PSC 3110 Fall 2010 Reading in Garrett & Grisham textbook Chapter pages 205- 240 – (quite complete discourse on carbohydrate structure and function with some emphasis on cell surfaces) several figures presented in these notes are taken from The G & G chapter In Lehninger’s book read chapter Web videos URLs Presented by Eric Allain – Assistant professor at Alalachian university http://vimeo.com/2993351 Presented by Prof S Dasgupta, Dept of Chemistry, IIT Kharagpur Institute of Technology at Kharagpur, India http://www.youtube.com/watch?v=iuW3nk5EADg http://www.youtube.com/watch?v=aeC7M9PDjQw&feature=channel Carbohydrates General characteristics • the term carbohydrate is derived from the french: hydrate de carbone • compounds composed of C, H, and O • (CH2O)n when n = then C5H10O5 • not all carbohydrates have this empirical formula: deoxysugars, aminosugars • carbohydrates are the most abundant compounds found in nature (cellulose: 100 billion tons annually) General characteristics • Most carbohydrates are found naturally in bound form rather than as simple sugars • Polysaccharides (starch, cellulose, inulin, gums) • Glycoproteins and proteoglycans (hormones, blood group substances, antibodies) • Glycolipids (cerebrosides, gangliosides) • Glycosides • Mucopolysaccharides (hyaluronic acid) • Nucleic acids Functions • sources of energy • intermediates in the biosynthesis of other basic biochemical entities (fats and proteins) • associated with other entities such as glycosides, vitamins and antibiotics) • form structural tissues in plants and in microorganisms (cellulose, lignin, murein) • participate in biological transport, cell-cell recognition, activation of growth factors, modulation of the immune system Classification of carbohydrates • Monosaccharides (monoses or glycoses) • Trioses, tetroses, pentoses, hexoses • Oligosaccharides • Di, tri, tetra, penta, up to or 10 • Most important are the disaccharides • Polysaccharides or glycans • Homopolysaccharides • Heteropolysaccharides • Complex carbohydrates Monosaccharides • also known as simple sugars • classified by the number of carbons and whether aldoses or ketoses • most (99%) are straight chain compounds • D-glyceraldehyde is the simplest of the aldoses (aldotriose) • all other sugars have the ending ose (glucose, galactose, ribose, lactose, etc…) Aldose sugars H C (H O C OH)n CH2OH Aldose C H H H H C OH C H C OH CH2OH H C OH Aldotriose n=1 C O H C OH H C H C O O CH2OH Aldotetrose n=2 H C O H C OH OH H C OH OH H C OH H C OH CH2OH Aldopentose n=3 CH2OH Aldohexose n=4 Lectins • Proteins that bind carbohydrates with high specificity and with moderate to high affinity • Found in all organisms (plants, animals, bacteria and viruses • Function in cell-cell recognition, signaling, and adhesion processes • Plant lectins: concanavalin A, wheat germ agglutinin, ricin • Animal lectins: galectin-1, selectins • Bacterial lectins: enterotoxin, cholera toxin • Viral lectins: influenza virus hemagglutinin, polyoma virus protein-1 Influenza virus • Is able to attach to host cells through interactions with oligosaccharides • Lectin on virus is HA (hemagglutinin) – protein essential for entry and infection • Once it has replicated in the host cell, the new virus must bud out to infect other cells • A viral sialidase (neuraminidase) trims the terminal sialic acid residue from the host cell’s oligosaccharide • This action releases the viral particle from its interation with the cell and prevent aggregation with other virus particles Influenza virus N-acetylneuraminic acid (a sialic acid) Neuraminidase enzyme Oseltamivir (Tamiflu) Zanamivir (Relenza) Influenza virus • Antiviral drugs: oseltamivir (Tamiflu) and zanamivir (Relenza) • Sugar analogs • Inhibit the viral sialidase by competing with the host cell’s oligosaccharides for binding • They prevent the release of viruses from the infected cell and also cause virus particles to aggregate both of which block another cycle of infection • These drugs must be used as soon as symptoms are detected (12- 24 hours) Selectins • Selectins are adhesion proteins found on rolling leukocytes and on the endothelial cells of the vascular walls • types are known • L-selectin found on the walls of leukocytes • E- and P-selectins found on the endothelial cells • Involved in the inflammatory response due to bacteria and viruses GLYCOLIPIDS • Cerebrosides • One sugar molecule – Galactocerebroside – in neuronal membranes – Glucocerebrosides – elsewhere in the body • Sulfatides or sulfogalactocerebrosides • A sulfuric acid ester of galactocerebroside • Globosides: ceramide oligosaccharides • Lactosylceramide – sugars ( eg lactose) • Gangliosides • Have a more complex oligosaccharide attached • Biological functions: cell-cell recognition; receptors for hormones glycolipids R HO O NH O R' SUGAR polar head is a sugar beta linkage There are different types of glycolipids: cerebrosides, gangliosides, lactosylceramides GLYCOLIPIDS • Cerebrosides • One sugar molecule – Galactocerebroside – in neuronal membranes – Glucocerebrosides – elsewhere in the body • Sulfatides or sulfogalactocerebrosides • A sulfuric acid ester of galactocerebroside • Globosides: ceramide oligosaccharides • Lactosylceramide – sugars ( eg lactose) • Gangliosides • Have a more complex oligosaccharide attached • Biological functions: cell-cell recognition; receptors for hormones Gangliosides • complex glycosphingolipids that consist of a ceramide backbone with or more sugars esterified,one of these being a sialic acid such as N-acetylneuraminic acid • common gangliosides: GM1, GM2, GM3, GD1a, GD1b, GT1a, GT1b, Gq1b Ganglioside nomenclature • letter G refers to the name ganglioside • the subscripts M, D, T and Q indicate mono-, di-, tri, and quatra(tetra)-sialiccontaining gangliosides • the numerical subscripts 1, 2, and designate the carbohydrate sequence attached to ceramide Ganglioside nomenclature • Numerical subscripts: • Gal-GalNAc-Gal-Glc-ceramide • GalNAc-Gal-Glc-ceramide • Gal-Glc-ceramide CH2OH CH2OH OH H O O O O OH O H H O H H CH2OH CH2OH OH O H H OH H NH C D-Galactose H3C H H OH HO O O COO- CHOH CH2OH H H N-acetylneuraminidate (sialic acid) O H C CH2 NH C C C H OH A ganglioside (GM1) OH H C H CHOH H H H O H C NH OH H CH3 O D-glucose D-galactose N-Acetyl-D-galactosamine R O Lipid storage diseases • also known as sphingolipidoses • genetically acquired • due to the deficiency or absence of a catabolic enzyme • examples: • • • • Tay Sachs disease Gaucher’s disease Niemann-Pick disease Fabry’s disease ... 2[Fe(CN)6 ]-3 2[Fe(CN)6 ]-4 PQQ + 2[Fe(CN)6 ]-4 + 2H+ 2[Fe(CN)6 ]-3 + 2e- Glucose oxidase (GOD) methods: colorimetric method glucose oxidase D-gluconolactone + H2O2 β -D-glucose + O2 D-gluconolactone... H2O glucose oxidase 2[Fe(CN)6 ]-4 D-gluconic acid + 2[Fe(CN)6 ]-4 + 2H+ 2[Fe(CN)6 ]-3 + 2e- glucose oxidase β -D-glucose + O2 H2O2 D-gluconolactone + H2O2 2H+ + O2 + 2e- ... URLs Presented by Eric Allain – Assistant professor at Alalachian university http://vimeo.com/2993351 Presented by Prof S Dasgupta, Dept of Chemistry, IIT Kharagpur Institute of Technology at