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.

I (CH2O)n or H - C - OH

I

Carbohydrates (glycans) have the following basic composition:

Monosaccharides

Aldoses (e.g., glucose) have an aldehyde group at one end.

Ketoses (e.g., fructose) have a keto group, usually at C2.

C

C OHH

C HHO

C OHH

C OHH

CH2OH

D-glucose

OH

C HHO

C OHH

C OHH

CH2OH

CH2OH

C O

D-fructose

D vs L Designation

D & L designations are based on the configuration about the single asymmetric C in glyceraldehyde.

The lower representations are Fischer Projections.

CHO

C

CH2OH

HO H

CHO

C

CH2OH

H OH

CHO

C

CH2OH

HO H

CHO

C

CH2OH

H OH

L-glyceraldehydeD-glyceraldehyde

L-glyceraldehydeD-glyceraldehyde

Sugar Nomenclature

For sugars with more than one chiral center, D or L refers to the asymmetric C farthest from the aldehyde or keto group.

Most naturally occurring sugars are D isomers.

O H O H C C H – C – OH HO – C – H

HO – C – H H – C – OH

H – C – OH HO – C – H

H – C – OH HO – C – H

CH2OH CH2OH

D-glucose L-glucose

D & L sugars are mirror images of one another.

They have the same name, e.g., D-glucose & L-glucose.

Other stereoisomers have unique names, e.g., glucose, mannose, galactose, etc.

The number of stereoisomers is 2n, where n is the number of asymmetric centers.

The 6-C aldoses have 4 asymmetric centers. Thus there are 16 stereoisomers (8 D-sugars and 8 L-sugars).

O H O H C C H – C – OH HO – C – H

HO – C – H H – C – OH

H – C – OH HO – C – H

H – C – OH HO – C – H

CH2OH CH2OH

D-glucose L-glucose

Hemiacetal & hemiketal formation

An aldehyde can react with an alcohol to form a hemiacetal.

A ketone can react with an alcohol to form a hemiketal.

R'O

H

R

C

H

OO C O

R

H

R'

H

alcohol aldehyde hemiacetal (C-O-C-O-H)

R'O

H

R

C

R''

OO C O

R

R''

R'

H

alcohol ketone hemiketal (C-O-C-O-H)

Ring Closure in glucose…hemiacetal formation

CH2OH

O

OH

OH

OH

OH

C

CH2OH

O

OH

OH

OH

O

H

O

OH

OH

OH

OH

CH2OH

From Fischer to Haworth

• OH on the right appear below the ring

• OH on left appear above ring

Ring Closure in Fructose…hemiketal formation

CH2OH

CC

CH2OH

OOH

OH

O

HCH2OH

C

C

CH2OH

O

OH

OH

OH

CO

C

CH2OH CH2OH

OHOH

OH

Anomers

• Anomeric carbon is carbonyl carbon

• Depending on orientation during nucleophilic attack, can get two orientations

• If ring closes with OH below ring, then is called α

• If ring closes with OH above ring, then is called β

Anomer formation in glucose

CH2OH

O

OH

OH

OH

OH

H

C

CH2OH

O

OH

OH

OH

O

H

HO

OH

OH

OH

OH

CH2OH

H

CH2OH

O

OH

OH

OH

OH

H

C

CH2OH

O

OH

OH

OH

O

H

H

O OH

OH

OH

OH

CH2OH

H

alpha glucose

beta glucose

Draw the following in the closed form… do the first as α galactose

an the second as β riboseCH2OH

OH H

OH

H OH

OH

O

H

H

CH2OH

H

H

OH

O

OH

OH

H

galactose

ribose

Answers

O

OHOH

OH

OHCH2OH

OOH

OHOH

CH2OH

alpha galactose

beta ribose

Sugar derivatives

sugar alcohol - lacks an aldehyde or ketone; e.g., ribitol.

sugar acid - the aldehyde at C1, or OH at C6, is oxidized to a carboxylic acid; e.g., gluconic acid, glucuronic acid.

CH2OH

C

C

C

CH2OH

H OH

H OH

H OH

D-ribitol

COOH

C

C

C

C

H OH

HO H

H OH

D-gluconic acid D-glucuronic acid

CH2OH

OHH

CHO

C

C

C

C

H OH

HO H

H OH

COOH

OHH

Sugar derivatives

amino sugar - an amino group substitutes for a hydroxyl. An example is glucosamine.

The amino group may be acetylated, as in N-acetylglucosamine.

H O

OH

H

OH

H

NH2H

OH

CH2OH

H

-D-glucosamine

H O

OH

H

OH

H

NH

OH

CH2OH

H

-D-N-acetylglucosamine

C CH3

O

H

N-acetylneuraminate (N-acetylneuraminic acid, also called sialic acid) is often found as a terminal residue of oligosaccharide chains of glycoproteins.

Sialic acid imparts negative charge to glycoproteins, because its carboxyl group tends to dissociate a proton at physiological pH, as shown here.

NH O

H

COO

OH

H

HOH

H

H

RCH3C

O

HC

HC

CH2OH

OH

OH

N-acetylneuraminate (sialic acid)

R =

Reducing Sugars

• Sugars that contain aldehyde groups that are oxidized to carboxylic acids are classified as reducing sugars.

• Common test reagents are : • Benedicts reagent (CuSO4 / citrate) • Fehlings reagent (CuSO4 / tartrate)

• They are classified as reducing sugars since they reduce the Cu2+ to Cu+  which forms as a red precipitate, copper (I) oxide.

• So any sugar that contains a hemi-acetal will be a reducing sugar.

Hemiacetals are reducing sugars

• In equilibrium with the aldehyde

CH2OH

O

OH

OH

OH

OH

O

OH

OH

OH

OH

CH2OH

Are hemiketals reducing?

• What are they in equilibrium with?

• Is this oxidizable?

Fructose, however is reducing

CH2OH

C

C

CH2OH

O

OH

OH

OH

CHOH

C

C

CH2OH

OH

OH

OH

OH

C

C

C

CH2OH

O

OH

OH

OH

OH

H

fructose ene-diol intermediateglucose

Acetal/ketal FormationR'O

COH

H

R

R''O

H

R'O

CR''OH

R

OH2

alcohol hemiacetal acetal

+

R'O

COH

R''

R

R'''O

H

R'O

CR'''OR''

R

OH2

alcohol hemiketal Ketal

+

Glycosidic BondsAcetal or ketal linkage between sugars

C

O

OHOH

OH

OH

CH2OHH

O

OHOH

OHO

CH2OH

H

O

OHOH

OH

O

CH2OH

O

OH

OH

OH

CH2OH

OH2

hemiacetal alcohol acetal

+

Disaccharide nomenclature• Sugars named• Linkages named as to from what carbon on sugar 1

to what carbon on sugar 2• Anomeric carbon has to be specified as α or β• Next slide has glucose-glucose in an α 1,4

linkage– Carbon 1 is α and attaches to carbon 4 on the next glucose

• Also shown is β 1,4 linkage– Carbon 1 is β and attaches to carbon 4 on the next glucose

Cellobiose, a product of cellulose breakdown, is the otherwise equivalent anomer (O on C1 points up).

The (1 4) glycosidic linkage is represented as a zig-zag, but one glucose is actually flipped over relative to the other.

Disaccharides:

Maltose, a cleavage product of starch (e.g., amylose), is a disaccharide with an (1 4) glycosidic link between C1 - C4 OH of 2 glucoses.

It is the anomer (C1 O points down).

O

OHOH

OH

O

CH2OH

O

OH

OH

OH

CH2OH

O

OHOH

OH

O

CH2OH

O

OH

OH

OH

CH2OH

alpha 1,4 glucose-glucose (maltose)

beta-1,4-glucose-glucose (cellobiose

Draw the following

• Glucose-glucose in an α-1,6 linkage

• Glucose-galactose in an α-1, β -1 linkage– (glucose is alpha and galactose in beta)

Answers

• Glucose-glucose in α 1,6 linkage

• Glucose α -1 – galactose β - 1

OH

O

OH

OH

CH2OH

O

CH2

OH

O

OH

OH

OH

O

OOH

OH

OH

CH2OH

O

OH

OH

OHCH2OH

Other disaccharides include:

Sucrose, common table sugar, has a glycosidic bond linking the anomeric hydroxyls of glucose & fructose.

Because the configuration at the anomeric C of glucose is (O points down from ring), the linkage is (12).

Lactose, milk sugar, is composed of galactose & glucose, with (14) linkage from the anomeric OH of galactose. Its full name is -D-galactopyranosyl-(1 4)--D-glucopyranose

Sucrose

Lactose

Lactose Intolerance

• Lactose or milk sugar occurs in the milk of mammals - 4-6% in cow's milk and 5-8% in human milk. It is also a by product in the the manufacture of cheese.

• Lactose intolerance is the inability to digest significant amounts of lactose, the predominant sugar of milk. This inability results from a shortage of the enzyme lactase, which is normally produced by the cells that line the small intestine. Lactase breaks down the lactose, milk sugar, into glucose and galactose that can then be absorbed into the bloodstream.

Polysaccharides

Plants store glucose as amylose or amylopectin, glucose polymers collectively called starch. Glucose storage in polymeric form minimizes osmotic effects.

Amylose is a glucose polymer with (14) linkages. It adopts a helical conformation.

The end of the polysaccharide with an anomeric C1 not involved in a glycosidic bond is called the reducing end.

H O

OH

H

OHH

OH

CH 2 OH

HO H

H

OHH

OH

CH 2 OH

H

O

HH H O

OH

OHH

OH

CH 2 OH

HH H O

H

OHH

OH

CH 2 OH

H

OH

HH O

OH

OHH

OH

CH 2 OH

H

O

H

1

6

5

4

3

1

2

a m y lo s e

Amylopectin is a glucose polymer with mainly (14) linkages, but it also has branches formed by (16) linkages. Branches are generally longer than shown above.

The branches produce a compact structure & provide multiple chain ends at which enzymatic cleavage can occur.

H O

OH

H

OHH

OH

CH2OH

HO H

H

OHH

OH

CH2OH

H

O

HH H O

OH

OHH

OH

CH2

HH H O

H

OHH

OH

CH2OH

H

OH

HH O

OH

OHH

OH

CH2OH

H

O

H

O

1 4

6

H O

H

OHH

OH

CH2OH

HH H O

H

OHH

OH

CH2OH

HH

O1

OH

3

4

5

2

amylopectin

Glycogen, the glucose storage polymer in animals, is similar in structure to amylopectin. But glycogen has more (16) branches.

The highly branched structure permits rapid release of glucose from glycogen stores, e.g., in muscle during exercise. The ability to rapidly mobilize glucose is more essential to animals than to plants.

H O

OH

H

OHH

OH

CH 2OH

HO H

H

OHH

OH

CH 2OH

H

O

HH H O

OH

OHH

OH

CH 2

HH H O

H

OHH

OH

CH 2OH

H

OH

HH O

OH

OHH

OH

CH 2OH

H

O

H

O

1 4

6

H O

H

OHH

OH

CH 2OH

HH H O

H

OHH

OH

CH 2OH

HH

O1

OH

3

4

5

2

glycogen

Review quiz

• Which hormone signals the release of glycogen into glucose?

• What was the mechanism of signal transduction?

Cellulose, a major constituent of plant cell walls, consists of long linear chains of glucose with (14) linkages.

1. How does the structure in cellulose affects it bonding?

2. Animals lack the enzymes needed to break down these linkages. How do animals, like cattle, subsist on cellulose?

.

.

OOH

OH

OH

O

CH2OH

O

OH

OH

O

CH2OH

O

OH

OH

O

CH2OH

O

OH

OH

O

CH2OH

O

OH

OH

O

CH2OH

O

OH

OH

OH

CH2OH

Answer 1

• The van der Waals interactions cause cellulose chains to be straight & rigid, and pack with a crystalline arrangement in thick bundles called microfibrils

• The role of cellulose is to impart strength and rigidity to plant cell walls, which can withstand high hydrostatic pressure gradients. Osmotic swelling is prevented.

Answer 2

• Animals, like cattle, have commensal bacteria in their gut that can break the linkages of cellulose.

•Similar to cellulose(14) linkages.

•The monomer is N-acetyl-D-glucosamine•Plays a structural role •Structural components of exoskeleton of invertebrates

ChitinO O

NH

OH

O

CH2OH

C

O

CH3

O

NH

OH

O

CH2OH

C

O

CH3

O

NH

OH

OH

CH2OH

C

O

CH3

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. 

O-linked oligosaccharides have roles in recognition, interaction, and enzyme regulation.

H O

OH

O

H

HNH

OH

CH2OH

H

C CH3

O

-D-N-acetylglucosamine

CH2 CH

C

NH

O

H

serine residue

Oligosaccharides that are covalently attached to proteins or to membrane lipids may be linear or branched chains.

H O

OH

O

H

HNH

OH

CH2OH

H

C CH3

O

-D-N-acetylglucosamine

CH2 CH

C

NH

O

H

serine residue

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

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.

H O

OH

HN

H

H

HNH

OH

CH2OH

H

C CH3

O

C CH2 CH

O HN

C

HN

O

HC

C

HN

HC

R

O

C

R

O

Asn

X

Ser or ThrN-acetylglucosamine

Initial sugar in N-linked glycoprotein oligosaccharide

Many proteins secreted by cells have attached N-linked oligosaccharide chains.

Carbohydrate chains of plasma membrane glycoproteins and glycolipids usually face the outside of the cell.

They have roles in cell-cell interaction and signaling, and in forming a protective layer on the surface of some cells.