Molecular Biochemistry I

Carbohydrates

Copyright © 1999-2008 by Joyce J.
Diwan.
All rights reserved.

Carbohydrates (glycans) have the following
basic composition: I
(CH2O)n or H - C - OH
I
 Monosaccharides - simple sugars with multiple OH
groups. Based on number of carbons (3, 4, 5, 6), a
monosaccharide is a triose, tetrose, pentose or hexose.
 Disaccharides - 2 monosaccharides covalently linked.
 Oligosaccharides - a few monosaccharides covalently
linked.
 Polysaccharides - polymers consisting of chains of
monosaccharide or disaccharide units.

Monosaccharides
Aldoses (e.g., glucose) have Ketoses (e.g., fructose) have
an aldehyde group at one end. a keto group, usually at C2.
H O
C CH2OH

H C OH C O

HO C H HO C H

H C OH H C OH

H C OH H C OH

CH2OH CH2OH

D-glucose D-fructose

D vs L Designation CHO CHO D & L designations H C OH HO C H are based on the configuration about CH2OH CH2OH the single asymmetric D-glyceraldehyde L-glyceraldehyde C in glyceraldehyde. D-glyceraldehyde L-glyceraldehyde . CHO CHO The lower H C OH HO C H representations are CH2OH CH2OH Fischer Projections.

C C D or L refers to the H – C – OH HO – C – H asymmetric C farthest HO – C – H H – C – OH from the aldehyde or H – C – OH HO – C – H keto group. H – C – OH HO – C – H CH2OH CH2OH Most naturally occurring D-glucose L-glucose sugars are D isomers. . Sugar Nomenclature For sugars with more O H O H than one chiral center.

D & L sugars are mirror O H O H images of one another.g. H – C – OH HO – C – H H – C – OH HO – C – H Other stereoisomers have unique names. CH2OH CH2OH e. D-glucose L-glucose galactose.g. etc. where n is the number of asymmetric centers. Thus there are 16 stereoisomers (8 D-sugars and 8 L-sugars). C C They have the same H – C – OH HO – C – H name. The 6-C aldoses have 4 asymmetric centers. The number of stereoisomers is 2n. ... D-glucose HO – C – H H – C – OH & L-glucose. glucose. mannose. e.

aldehyde alcohol hemiacetal R R A ketone can react with an C O + "R OH "R O C OH alcohol to form R' R' a hemiketal. Hemiacetal & hemiketal formation H H An aldehyde can C O + R' OH R' O C OH react with an alcohol to form R R a hemiacetal. ketone alcohol hemiketal .

as the 5 5 H O H H O OH C1 aldehyde & H H 4 1 4 1 C5 OH react. . -D-glucose -D-glucose These representations of the cyclic sugars are called Haworth projections. H 5 C OH Glucose forms an 6 CH2OH intra-molecular 6 CH2OH 6 CH2OH hemiacetal. to OH H OH H form a 6-member OH 3 2 OH OH 3 2 H pyranose ring. 1 CHO Pentoses and H C OH hexoses can cyclize 2 HO C H as the ketone or 3 D-glucose aldehyde reacts H C OH (linear form) 4 with a distal OH. H OH H OH named after pyran.

or  a 5-member furanose ring. .Fructose forms either  a 6-member pyranose ring. by reaction of the C2 keto group with the OH on C6. by reaction of the C2 keto group with the OH on C5.

 & . 6 CH 2 OH 6 CH 2 OH 5 O 5 O H H H OH H H 4 H 1 4 H 1 OH OH OH OH OH H 3 2 3 2 H OH H OH -D -glucose -D -glucose Cyclization of glucose produces a new asymmetric center at C1. . Haworth projections represent the cyclic sugars as having essentially planar rings. with the OH at the anomeric C1:  (OH below the ring)   (OH above the ring). The 2 stereoisomers are called anomers.

depending on the sugar. pyranose sugars actually assume a "chair" or "boat" configuration. The representation above reflects the chair configuration of the glucopyranose ring more accurately than the Haworth projection. H OH H OH 4 6 H O H O HO 5 HO HO 2 H HO OH 3 H OH 1 H OH H OH H H -D-glucopyranose -D -glucopyranose Because of the tetrahedral nature of carbon bonds. .

.the aldehyde at C1.g. Sugar derivatives COOH CHO CH2OH H C OH H C OH H C OH HO C H HO C H H C OH H C OH H C OH H C OH H C OH H C OH CH2OH CH 2OH COOH D-ribitol D -gluconic acid D -glucuronic acid  sugar alcohol .  sugar acid .lacks an aldehyde or ketone. e. e.g. ribitol. . or OH at C6. gluconic acid. glucuronic acid. is oxidized to a carboxylic acid..

. as in N-acetylglucosamine. The amino group may be acetylated.an amino group substitutes for a hydroxyl. Sugar derivatives CH 2OH CH 2OH H O H H O H H H OH H OH H OH OH OH O OH H NH 2 H N C CH 3 H -D-glucosamine -D-N-acetylglucosamine amino sugar . An example is glucosamine.

O H H3C C NH O COO R HC OH H H R= HC OH H OH CH2OH OH H N-acetylneuraminate (sialic acid) N-acetylneuraminate (N-acetylneuraminic acid. because its carboxyl group tends to dissociate a proton at physiological pH. also called sialic acid) is often found as a terminal residue of oligosaccharide chains of glycoproteins. as shown here. . Sialic acid imparts negative charge to glycoproteins.

splitting out water to form a glycosidic bond: R-OH + HO-R'  R-O-R' + H2O E. Glycosidic Bonds The anomeric hydroxyl and a hydroxyl of another sugar or some other compound can join together. H OH H OH H O H2O H O HO HO HO H + CH 3 -O H HO H H OH H OH H OH H O CH 3 -D-glucopyranose methanol methyl--D-glucopyranose . methanol reacts with the anomeric OH on glucose to form methyl glucoside (methyl-glucopyranose)..g.

a product of cellulose breakdown.g. 4 OH H 1 O 4 OH H 1 H H It is the  anomer OH 3 2 3 2 H OH (C1 O points down). . amylose). cellobiose H OH Cellobiose. is a H OH m altose H OH disaccharide with an (1 4) glycosidic 6 CH 2 O H 6 CH 2O H 5 O 5 O link between C1 .C4 H H H H OH OH of 2 glucoses. a cleavage 4 OH H 1 4 OH H 1 product of starch OH 3 2 O 3 2 OH (e. is the otherwise equivalent  anomer (O on C1 points up). 6 CH 2 O H 6 CH 2 O H Disaccharides: H 5 O H H 5 O H H H Maltose.. The (1 4) glycosidic linkage is represented as a zig-zag. but one glucose is actually flipped over relative to the other.

Other disaccharides include:  Sucrose. the linkage is (12). is composed of galactose & glucose. Its full name is -D-galactopyranosyl-(1 4)- -D-glucopyranose . milk sugar.)  Lactose. has a glycosidic bond linking the anomeric hydroxyls of glucose & fructose. The full name of sucrose is -D-glucopyranosyl-(12)- -D-fructopyranose. common table sugar. with (14) linkage from the anomeric OH of galactose. Because the configuration at the anomeric C of glucose is  (O points down from ring).

glucose polymers collectively called starch. Glucose storage in polymeric form minimizes osmotic effects. Amylose is a glucose polymer with (14) linkages. . The end of the polysaccharide with an anomeric C1 not involved in a glycosidic bond is called the reducing end. CH 2 OH 6 CH OH CH 2 OH CH 2 OH CH 2 OH 2 O 5 O H O H O H H O H H H H H H H H H H H OH H 1 4 OH H 1 OH H OH H OH H O O O O OH OH 2 3 H OH H OH H OH H OH H OH a m y lo s e Polysaccharides: Plants store glucose as amylose or amylopectin.

. CH 2OH CH 2OH H O H H O H amylopectin H H OH H OH H 1 O OH O H OH H OH CH 2OH CH 2OH 6 CH 2 CH 2OH CH 2OH H O H H O H H 5 O H H O H H O H H H H H H OH H OH H OH H 1 4 OH H OH H 4 O O O O OH OH 2 3 H OH H OH H OH H OH H OH Amylopectin is a glucose polymer with mainly (14) linkages. The branches produce a compact structure & provide multiple chain ends at which enzymatic cleavage can occur. but it also has branches formed by (16) linkages. Branches are generally longer than shown above.

But glycogen has more (16) branches. e.g. is similar in structure to amylopectin. CH 2 OH CH 2 OH H O O glycogen H H H H H OH H OH H 1 O OH O H OH H OH CH 2 OH CH 2 OH 6 CH 2 CH 2 OH CH 2 OH H O H H O H H 5 O H H O H H O H H H H H H OH H OH H OH H 1 4 OH H OH H 4 O O O O OH OH 3 2 H OH H OH H OH H OH H OH Glycogen.. . the glucose storage polymer in animals. in muscle during exercise. The highly branched structure permits rapid glucose release from glycogen stores. The ability to rapidly mobilize glucose is more essential to animals than to plants.

consists of long linear chains of glucose with (14) linkages. See: Botany online website. . This promotes intra-chain and inter-chain H-bonds and van der Waals interactions. and pack with a crystalline arrangement in thick bundles . website at Georgia Tech. a major constituent of plant cell walls.microfibrils. CH 2 OH 6 CH OH CH 2 OH CH 2 OH CH 2 OH 2 O 5 O O H O H O OH H H H H H H H H OH H 1 O 4 OH H 1 O OH H O OH H O OH H OH H H H H 2 H 3 H OH H OH H OH H OH H OH c e llu lo s e Cellulose. Every other glucose is flipped over. due to  linkages. that cause cellulose chains to be straight & rigid.

which can withstand high hydrostatic pressure gradients. These microfibrils are very strong. Explore and compare structures of amylose & cellulose using Chime. The role of cellulose is to impart strength and rigidity to plant cell walls. Osmotic swelling is prevented. CH 2 OH 6 CH OH CH 2 OH CH 2 OH CH 2 OH 2 O 5 O O H O H O OH H H H H H H H H OH H 1 O 4 OH H 1 O OH H O OH H O OH H OH H H H H 2 H 3 H OH H OH H OH H OH H OH c e llu lo s e Multisubunit Cellulose Synthase complexes in the plasma membrane spin out from the cell surface microfibrils consisting of 36 parallel. interacting cellulose chains. .

etc. CH 2 O H D -glucuronate 6  H 5 O 6 COO H 4 1 O O H H 5 H OH H 4 H 1 3 2 OH H H NH COCH 3 3 2 O H OH N -acetyl. The constituent monosaccharides tend to be modified. sulfated hydroxyl and amino groups. .D -glucosam ine hyaluronate Glycosaminoglycans (mucopolysaccharides) are linear polymers of repeating disaccharides. because of the prevalence of acidic groups. amino groups. with acidic groups. Glycosaminoglycans tend to be negatively charged.

glucuronate (glucuronic acid) & N-acetyl-glucosamine. CH 2 O H D -glucuronate 6  H 5 O 6 COO H 4 1 O O H H 5 H OH H 4 H 1 3 2 OH H H NH COCH 3 3 2 O H OH N -acetyl. . The glycosidic linkages are (13) & (14).D -glucosam ine hyaluronate Hyaluronate (hyaluronan) is a glycosaminoglycan with a repeating disaccharide consisting of 2 glucose derivatives.

. heparan sulfate core glycosaminoglycan protein transmembrane -helix cytosol Proteoglycans are glycosaminoglycans that are covalently linked to serine residues of specific core proteins. The glycosaminoglycan chain is synthesized by sequential addition of sugar residues to the core protein.

another proteoglycan. CH 2 O H D -glucuronate 6  H 5 O Websites on: 6 COO H 1 O 4 H H O Aggrecan H 5 OH H 4 H 1 3 2 OH Aggrecan & v H O H NH COCH 3 2 ersican H 3 OH N -acetyl. E.D -glucosam ine .g. hyaluronate .Some proteoglycans of the extracellular matrix bind non- covalently to hyaluronate via protein domains called link modules. • Versican. binds hyaluronate in the extracellular matrix of loose connective tissues.: • Multiple copies of the aggrecan proteoglycan associate with hyaluronate in cartilage to form large complexes.

Later. iduronate-2-sulfate N-sulfo-glucosamine-6-sulfate H CH2OSO3 H O H O H COO H OH H O OH H H O H OSO3 H NHSO3 heparin or heparan sulfate . glucuronate residues may be converted to the sulfated sugar iduronic acid. . while N- acetylglucosamine residues may be deacetylated and/or sulfated.examples of residues Heparan sulfate is initially synthesized on a membrane- embedded core protein as a polymer of alternating N-acetylglucosamine and glucuronate residues. in segments of the polymer.

it inhibits clot formation by interacting with the protein antithrombin.Heparin. alternating IDS (iduronate-2- sulfate) & SGN (N-sulfo-glucosamine-6-sulfate). has a structure similar to that of heparan sulfates. Heparin has an extended helical C  O  N  S conformation. When released into the blood. Charge repulsion by the many negatively charged groups may contribute to this conformation. . a soluble glycosaminoglycan found in granules of mast cells. Heparin shown has 10 residues. but is more highly sulfated.

cytosol  The core protein of a syndecan heparan sulfate proteoglycan includes a single transmembrane -helix.  The core protein of a glypican heparan sulfate proteoglycan is attached to the outer surface of the plasma membrane via covalent linkage to a modified phosphatidylinositol lipid. as in the simplified diagram above. . heparan sulfate core glycosaminoglycan Some cell surface heparan protein sulfate glycosaminoglycans remain covalently linked to transmembrane core proteins embedded in -helix the plasma membrane.

heparin or heparan sulfate ...g. binding of some growth factors (small proteins) to cell surface receptors is enhanced by their binding also to heparan sulfates. Regulated cell surface Sulf enzymes may remove sulfate groups at particular locations on heparan sulfate chains to alter affinity iduronate-2-sulfate N-sulfo-glucosamine-6-sulfate for signal H CH2OSO3 proteins.Proteins involved in signaling & adhesion at the cell surface recognize & bind heparan sulfate chains.examples of residues . H COO H OH H O OH H Diagram H O by Kirkpatrick H OSO3 H NHSO3 & Selleck.g. E. e. O H O H growth factors.

interaction.Oligosaccharides that are covalently attached to proteins or to membrane lipids may be linear or branched chains. O-linked oligosaccharides have roles in recognition. and enzyme regulation. O-linked oligosaccharide chains of glycoproteins vary in complexity. . They link to a protein via a glycosidic bond between a sugar residue & a serine or threonine OH.

including enzymes & transcription factors. with these 2 modifications having opposite regulatory effects (stimulation or inhibition). . are regulated by reversible GlcNAc attachment. Often attachment of GlcNAc to a protein OH alternates with phosphorylation.N-acetylglucosamine (GlcNAc) is a common O-linked glycosylation of protein serine or threonine residues. Many cellular proteins.

CH2OH O HN H O HN C CH2 CH Asn H H C O OH H HN OH HC R X H HN C CH3 C O O N-acetylglucosamine HN Initial sugar in N-linked HC R Ser or Thr glycoprotein oligosaccharide C O N-linked oligosaccharides of glycoproteins tend to be complex and branched. . First N-acetylglucosamine is linked to a protein via the side-chain N of an asparagine residue in a particular 3- amino acid sequence.

to yield a characteristic branched structure. and the N-linked oligosaccharide chain is modified by removal and addition of residues. .Additional monosaccharides are added.

They have roles in cell-cell interaction and signaling. and in forming a protective layer on the surface of some cells. Genetic diseases have been attributed to deficiency of particular enzymes involved in synthesizing or modifying oligosaccharide chains of these glycoproteins. Carbohydrate chains of plasma membrane glycoproteins and glycolipids usually face the outside of the cell. and gene knockout studies in mice. have been used to define pathways of modification of oligosaccharide chains of glycoproteins and glycolipids. Such diseases. .Many proteins secreted by cells have attached N-linked oligosaccharide chains.

Recognition/binding of CHO moieties of glycoproteins. glycolipids & proteoglycans by animal lectins is a factor in: • cell-cell recognition • adhesion of cells to the extracellular matrix • interaction of cells with chemokines and growth factors • recognition of disease-causing microorganisms • initiation and control of inflammation. .Lectins are glycoproteins that recognize and bind to specific oligosaccharides. The C-type lectin-like domain is a Ca++-binding carbohydrate recognition domain in many animal lectins. Concanavalin A & wheat germ agglutinin are plant lectins that have been useful research tools.

It binds cell surface carbohydrates of disease-causing microorganisms & promotes phagocytosis of these organisms as part of the immune response.Examples of animal lectins: Mannan-binding lectin (MBL) is a glycoprotein found in blood plasma. .

Selectins are integral proteins of mammalian cell plasma membranes with roles in cell-cell recognition & binding. A cytosolic domain participates in regulated interaction with the actin cytoskeleton. The C-type lectin-like domain is at the end of a multi-domain extracellular segment extending out from the cell surface. A cleavage site just outside the transmembrane -helix provides a mechanism for regulated release of some lectins from the cell surface. .