Chapter 7 Carbohydrates and Glycobiology

Carbohydrates are everywhere

Sucrose glazed donuts Sucrose (table sugar)

What are carbohydrates? Carbo-hydrates are a group of organic compound that can usually represented as (CH 2 O) n. Glucose, fructose, and galactose are all carbohydrates.  -D-Galactose

Classification of carbohydrate –carbon number –L- or D- isomers –pyranose or furanose –α or β anomers –ketose or aldose

Carbon number In addition to simple hexose such as glucose, galactose, and mannose, there are a number of sugar derivatives in which a hydroxyl group in the parent compound is replaced with another substituent, or carbon atom is oxidized to a carboxyl group. Therefore, researchers must give each carbon of a sugar a number.

Carbon number HO C H C C H C H C H CH 2 OH HO OH CH 2 OH H C C H C H C H HO O OH CH 2 OH aldose ketose

L- and D- isomers CHO H | -C- | OH CH 2 OH CHO H | -C- | HO CH 2 OH -glyceraldehyde D L [  ] 25 D =+8.7 ˚ [  ] 25 D =-8.7 ˚

L- and D-isomers Although L- and D-isomers of glyceraldehydes are truly levo-rotatory (-) and dextro-rotatory (+), L- and D- sugars are NOT. For example, L-arabinose [  ] 20 D = ˚ and D-fructose [  ] 20 D =-92 ˚  -L-arabinose (pyranose form)

How to determine L- and D- First, find the chiral carbon C H-=O | H--OH C H- -HC | | OH C

How to determine L- and D- If there is more than one chiral carbon, then… H-C H-C-OH | H 2 -C-OH | H-C-OH | =O H 2 -C-OH C=O H-C-OH H 2 -C-OH HO- | | | | -HC D- L-

C 5 Formation of the cyclic form HO H C C H C H H CH 2 OH HO OH C 1 C H HO O C H OHOH C HOH C H C HOHOH CH 2 OH  anomer

Other sugar generate 5-member ring C 5 H C C H C H CH 2 OH HO O OH 2 CH 2 OH H O C OH C HOH C H C HOCH CH 2 OHOH CH 2 OH  anomer

(few)

The importance of a sialic acid a sialic acid Normal protein Asialo- glycoprotein: Will be removed by asialoglycoprotein receptors in the liver Sialidase (neuraminidase)

Monosaccharides Colorless, crystalline solids Water soluble but not soluble in nonpolar solvent Taste sweet

Monosaccharides have reducing powers

Disaccharide is made by joining two monosaccharides

Lactose is only present in milk

Sucrose is also called table sugar

Trehalose is a major constituent of insect hemolymph

3 ≦ oligosaccharide ≦ 20

Polysaccharides Polysaccharides can serve as fuels, structural elements, and extracellular support.

Polysaccharides Homopolysaccharides –Starch (amylose, amylopectin) –Glycogen –Chitin Heteropolysaccharides –Peptidoglycan –Agar (agarose, agaropectin) –Glycosaminoglycans

Starch and glycogen are polymers of  -D-glucose The main chain of starch and glycogen are consisted of  -D-glucose joined by (  1  4) glycosidic bonds.

The branch point of starch and glycogen : (  1  6) Amylopectin and glycogen have branchs.

Cellulose is a polymer of  -D- glucose

amylose cellulose

Chitin : polymer of  -N-acetyl-D- glucosamine GlcNAc

Peptidoglycan contains heteropolysaccharides

Agarose is very important in molecular biology applications

Glycosaminoglycans are heteropolysaccharides N-acetylglucosamine or N-acetyllgalactosamine + uronic acid (D- glucuronic or L-iduronic acid)

Heparin is a natural anticoagulant

Glycoconjugates Proteoglycans – glycosaminoglycan chains covalently joined to a membrane or secreted protein Glycoproteins – complex oligosaccharides covalently joined to a protein Glycolipids – membrane lipids with oligosaccharides as hydrophilic head

Proteoglycans Point of attachment Site of attachment Trisaccharide bridge

Proteoglycan aggregates

Glycoproteins Glycoproteins are carbohydrate-protein conjugates in which the carbohydrate moieties are smaller and more structurally diverse than the glycosaminoglycans of proteoglycans. Anomeric carbon of carbohydrate + -OH of Ser/Thr or –NH 2 of Asn

Glycophorin A Glycophorin A has 16 oligosaccharides covalently attached to it, with total 60 to 70 monosaccharide residues. It is the MN antigen of human erythrocytes. Ser1, Gly5  M

O- and N-linked glycosidic linkages

Glycolipid and lipopolysaccharides are membrane components

Glycobiology Carbohydrates can be served as informational molecules

Sugar serves as “aging” marker of proteins a sialic acid Normal protein Asialo- glycoprotein: Will be removed by asialoglycoprotein receptors in the liver Sialidase (neuraminidase)

Lectins Lectins are proteins that bind carbohydrates with high affinity and specificity.

Membrane lectins of H. pylori binds to membrane glycoprotein of gastric epithelial cell Membrane lectins (P-, E- and L- selectins) play important role in the movement of immune cells