Carbohydrates and Glycobiology Carbohydrate function and classification Monosaccharides –Chemical structure and properties –Linear and cyclized forms –Common monosaccharides and disaccharides Carbohydrates can be joined to phosphates, alcohols and amines –Hexose derivatives important in biology Polysacchardies: Glycogen, Starch, Cellulose, and Chitin

“The chemistry and biology of carbohydrates has been a Cinderella field: an area that involves much work but, alas, does not get to show off at the ball with her cousins, the genomes and proteins.” Stella Hurtley, Robert Service, Phil Szuromi, Science Vol 291, 23 March 2001

“What has rescued this Cinderella from the shadows is no fairy godmother but a plethora of new synthetic and analytic methods that a previous generations of researchers would have found nearly magical nonetheless.” “Glycobiology has finally become part of the mainstream”

Functions: –As energy stores and fuels –As metabolic intermediates –As part of many important molecules (ATP, ribose sugar..) –In polysaccharides (e.g. cell walls of bacterial and plant) –Linked to proteins and lipids (glycoconjugates) In the extra cellular milieu, they exert effects on cellular recognition in infection, cancer, and immune response. Carbohydrates are central to many processes that are at the core of important diseases  drug design targeting a wide spectrum of diseases Classification: mono- and polysaccharides Carbohydrates

Two families of monosaccharides –Aldehydes with multiple OH groups (aldose) –Ketones with multiple OH groups (ketose) Chemical structures of monosaccharides –Triose, tetrose, pentose, hexose, heptose Smallest one: (CH 2 O) 3 e.g.: D(L)-glyceraldehyde Hexoses are the most common monosaccharides in nature D-ribose and 2-deoxy-D-ribose are components of nucleotides and nucleic acids –All except one monosaccharides have asymmetric centers Fisher projection representation Perspective representation Monosaccharides

Cyclized forms are predominant for pentoses and hexoses Furanose (hemiacetal): cyclized pentose Pyranose (hemiketal): cyclized hexose Haworth projections Anomers Conformation of pyranose/furanose rings –Pyranose ring: Chair vs. boat form –Furanose ring: puckered

Common monosaccharides –D-ribose, D-glucose, D-mannose, D-galactose, D-fructose Common disaccharides and enzymes that hydrolyze them –Sucrose: glucose-fructose (sucrase) –Lactose: galactose-glucose (lactase) –Maltose: glucose-glucose (maltase) –Enzymes are located on epithelial cells lining the small intestine Many monosaccharides are reducing agents Common Monosaccharides and Disaccharides Lactose intolerance: lack of lactase

Sugars can be phosphorylated –Key intermediates in energy generation and biosynthesis Carbohydrates can be joined to alcohols and amines by glycosidic bonds –N-glycosidic –O-glycosidic Important hexose derivatives in biology (next slide) Carbohydrates Can be Joined to Phosphates, Alcohols and Amines

Some hexose derivatives important in biology a uronic acida aldonic acid

Polysaccharides: Glycogen Polysaccharides –Homosaccharides (branched and unbranched) –Heterosaccharides (branched and unbranched) Glycogen –Store of glucose in animal cells  1  4 linkage with  1  6 branch –Exist in granules inside the cell tightly bound with enzymes for glycogen synthesis and degradation

Polysaccharides: Starch Starch –Store of sugar in plants –Two forms Amylose: unbranched –Glucose,  -1,4 linkage Amylopectin: branched –Glucose, 1  -1,6 per 30  -1,4 –  -amylase: hydrolyze  -1,4 linkages

Curved Polysaccharide Chain in amylose-Unbranched Starch

Polysaccharides: Cellulose and Chitin Cellulose –Plant polysaccharide –Serve as a structural not nutritional role –Unbranched polymer of glucose,  -1,4 linkages –Linear chains; forming fibers; high tensile strength –Mammals lack cellulases and so cannot digest wood and vegetable fibers Chitin –Exoskeletons of insects –Unbranched polymer of NAG,  -1,4 linkages –Long straight chains; structural roles

Intra-chain H-bonds Inter-chain H-bonds Linear Structure of Cellulose (D-glucose   Linkage) Extended chain Give extended chain

Bacterial Cell Walls Contain Peptidoglycans Structure of the cell wall of staphylococcus aureus NAG: N-acetylglucosamine NAM: N-acetylmuramic acid  1 4 linkage A number of layers; Provide strength to the cell; Keep shape of the cell; Antibacterial agent act on cell wall –peptidoglycan; Pennicillin; Lysozyme

Glycosaminoglycans are components of the extracellular matrix the extracellular space in the tissues of multicellular animals a gel-like material Heteropolysaccharide; linear Repreating disaccharides; N-acetylglucosamine (NAG) or N-acetylgalactosamine; Uronic acid (in most cases): D-glucuronic acid, or L-iduronic acid C-6 carbon in glucose/galactose/ mannose is oxidized to carboxyl One or more –OH is esterified with sulfate High density of negative charges on glycosaminoglycans (-COO -, -OSO 3 - ) extended conformation

In some glycosaminoglycans, The amino sugar is esterified with sulfate Uronic acid (most cases) NAG or N-acetylgalactosamine High density of negative charges extended conformation in solution Glycosaminoglycans are attached To extracellular proteins to form proteoglycans Very long! short Hyaluronate Chondroitin 4-sulfate Keratin sulfate