Carbohydrates

By : AHMAD FAROOQBy : AHMAD FAROOQ

Department of Biochmistry and

Molecular Biology

UoG, Gujrat.

• Carbohydrates Contain

the Elements:

�Carbon

�Hydrogen�Hydrogen

�Oxygen

GENERAL CHARACTERISTICS

• The termcarbohydrate is derived fromthe french:hydrate de carbone

• Compounds composed of C, H, and O• (CH O) whenn = 5 thenC H O• (CH2O)n whenn = 5 thenC5H10O5

• Not all carbohydrates have this empirical formula:deoxysugars, aminosugars etc,,

• Carbohydrates are the most abundant compoundsfound in nature (cellulose: 100 billion tonsannually)

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• 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 basicbiochemical entities (fats and proteins)

• Associated with other entities such as glycosides,• Associated with other entities such as glycosides,vitamins and antibiotics)

• Form structural tissues in plants and inmicroorganisms (cellulose, lignin, murein)

• Participate in biological transport, cell-cellrecognition, activation of growth factors,modulation of the immune system

I (CH2O)n or H - C - OH

I

Carbohydrates (glycans) have the following

basic composition:

•The n represents the number of

times the CH2O unite is repeated.times the CH2O unite is repeated.

� 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

Classification of Carbohydrates

� Oligosaccharides - a few monosaccharidescovalently linked.

• Polysaccharides - polymers consisting of chains of monosaccharide or disaccharide units. Polysaccharides

• Homopolysaccharides• Heteropolysaccharides• Complex carbohydrates

Monosaccharides

• Also known as simple sugars

• Classified by .

� 1. The number of carbons and

� 2. Whether aldoses or ketoses� 2. 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…)

Monosaccharides

The most important monosaccharide

monosaccharide is made up of 1 sugar unit.

• Monos are reducing sugars. • Monos are reducing sugars.

• Fructose and galactose are all so

monosaccharides, they all have the same

chemical formula but different structures.

Monosaccharides

Aldoses (e.g., glucose) have an

aldehyde group at one end.

Ketoses (e.g., fructose) have

a keto group, usually at C2.

COH

CH2OH

C OHH

C HHO

C OHH

C OHH

CH2OH

D-glucose

C HHO

C OHH

C OHH

CH2OH

C O

D-fructose

C O

CH2OHCH2OH

C O

CH2OH

C O

CH2OH

C O CH2OH

Ketose sugars

C

C

CH2OH

OH)n(H

O

Ketose

C O

CH2OH

Ketotriose n = 0

C O

C OHH

CH2OH

Ketotetrose n = 1

C OHH

CH2OH

C OHH

Ketopentose n = 2

C OHH

CH2OH

C O

C OHH

OHH

Ketohexose n = 3

C

C

CH2OH

OH)n(H

O

H

C

C

CH2OH

OHH

O

H

C OHH

C O

H

C OHH

C O

H

C OHH

C OHH

C O

H

C OHH

C OHH

Aldose sugars

Aldose Aldotriosen = 1

CH2OH

Aldotetrosen = 2

C

CH2OH

OHH

Aldopentose n = 3

CH OH

C

CH2OH

OHH

Aldohexose n = 4

D vs L Designation

D & L designations are

based on the

configuration about

CHO

C

CH2OH

HO H

CHO

C

CH2OH

H OH

configuration about

the single asymmetric

C in glyceraldehyde.

.

CHO

C

CH2OH

HO H

CHO

C

CH2OH

H OH

22

L-glyceraldehydeD-glyceraldehyde

L-glyceraldehydeD-glyceraldehyde

D and L Sugars

�D sugars can be degraded to the

dextrorotatory (+) form of glyceraldehyde.dextrorotatory (+) form of glyceraldehyde.

�L sugars can be degraded to the levorotatory

(-) form of glyceraldehyde.

Sugar Nomenclature

For sugars with more

than one chiral center,

D or L refers to the

O H O H C C H – C – OH HO – C – HD or L refers to the

asymmetric C farthest

from the aldehyde or

keto group.

Most naturally occurring

sugars are D isomers.

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 stereoisomershave unique names, e.g., glucose, mannose,

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 CH2OHe.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).

CH2OH CH2OH

D-glucose L-glucose

Hemiacetal & hemiketal formation

An aldehyde can

react with an

alcohol to form

O C

H

R

OHC

H

R

O R'R' OH+

alcohol to form

a hemiacetal.

A ketone can

react with an

alcohol to form

a hemiketal.

R

O C

R

R'

OHC

R

R'

O

aldehyde alcohol hemiacetal

ketone alcohol hemiketal

R

"R OH "R+

Pentoses and hexoses can cyclizeas the ketone or aldehyde reacts with a distal OH.

Glucose forms an intra-molecular hemiacetal, as the C1 aldehyde & C5

CH2OH CH2OH6 6

H

CHO

C OH

C HHO

C OHH

C OHH

CH2OH

1

5

2

3

4

6

D-glucose (linear form)

C1 aldehyde & C5 OH react, to form a 6-member pyranose ring, named after pyran.

These representations of the cyclic sugars are called

Haworth projections.

H O

OH

H

OHH

OH

2

H

OH

H H O

OH

H

OHH

OH

2

H

H

OH

α-D-glucose β-D-glucose

23

4

5

1 1

5

4

3 2

CH2OH

C O

C HHO

C OHH

C OHH

CH2OH

HOH2C

OH

CH2OH

HOH H

H HO

O

1

6

5

4

3

2

6

5

4 3

2

1

Fructose forms either

� a 6-member pyranose ring, by reaction of the C2 keto

group with the OH on C6, or

� a 5-member furanose ring, by reaction of the C2 keto

group with the OH on C5.

26

D-fructose (linear) α-D-fructofuranose

H O

OH

H

OHH

OH

CH2OH

H

α-D-glucose

OH

H H O

OH

H

OHH

OH

CH2OH

H

H

OH

β-D-glucose

23

4

5

6

1 1

6

5

4

3 2

Cyclization of glucose produces a new asymmetric center

at C1. The 2 stereoisomers are called anomers, α & β.

Haworth projections represent the cyclic sugars as having

essentially planar rings, with the OH at the anomeric C1:

� α (OH below the ring)

� β (OH above the ring).

O

H

HO

H

HO

H

OH

OHHH

OH

O

H

HO

H

HO

H

H

OHHOH

OH

α-D-glucopyranose β-D-glucopyranose

1

6

5

4

32

Because of the tetrahedral nature of carbon bonds,

pyranose sugars actually assume a "chair" or "boat"

configuration, depending on the sugar.

The representation above reflects the chair

configuration of the glucopyranose ring more accurately

than the Haworth projection.

C O

H

C OHH

C O

H

C HOH

C O

H

C HHO

C HHO

C O

H

C HHO

C HHO

Enantiomers and epimers

C

CH 2OH

OHH C

CH 2OH

HOH

these two aldotetroses are enantiomers.They are stereoisomers that are mirrorimages of each other

CH OH

C

CH 2OH

OHH

CHO H

C

CH 2OH

OHH

these two aldohexoses are C-4 epimers.they differ only in the position of thehydroxyl group on one asymmetric carbon(carbon 4)

Properties

•• Differences in structures of sugars are Differences in structures of sugars are responsible for variations in propertiesresponsible for variations in properties

• Physical• Crystalline form; solubility; rotatory power• Crystalline form; solubility; rotatory power

• Chemical• Reactions (oxidations, reductions, condensations)

• Physiological• Nutritive value (human, bacterial); sweetness;

absorption

Structural representation of sugars

• Fisher project ion: straight chain representat ion

• Haworth project ion: simple r ing in perspectiveperspective

• Conformational representat ion: chair and boat conf igurat ions

Rules for drawing Haworth projections

• draw either a six or 5-membered ring including oxygen as one atom

O O

• most aldohexoses are six-membered

• aldotetroses, aldopentoses, ketohexoses are 5-membered

O O

Rules for drawing Haworth projections

• next number the ring clockwise starting next to

the oxygen

O O5

141

23

4 1

23

4

Rules for drawing Haworth projections

• for D-sugars the highest numbered carbon

(furthest from the carbonyl) is drawn up. For

L-sugars, it is drawn down

• for D-sugars, the OH group at the anomeric • for D-sugars, the OH group at the anomeric

position is drawn down for α and up for β. For

L-sugars α is up and β is down

Chapter 22 29

Chapter 22 30

H

OH

OH

OH

α-D-glucofuranose β -D-glucopyranose

Mutarotation• α and β anomers have different specific rotatory power => reaching

equilibrium is accompanied by changes in optical rotatory power of solution

H

OH

H

OH

OH

OH

α-D-glucopyranoseβ-D-glucofuranose

Mutarotation of glucose results in an

equilibrium mixture of 36% α-glucose

and 64% β-glucose

–The more stable β-glucose form

predominatespredominates

–A very small amount of the open-chain form

exists in this equilibrium

• Mutarotation

When a sugar is dissolved in water, the specific rotation of the

solution gradually changes until it reaches to a constant value

due to equilibrium between the αααα and ββββ forms.

e.g. freshly prepared solution of ββββ -glucose has a specific rotation

+112o. When this solution is allowed to stand the rotation falls till

reach + 52.7o.

The equilibrium reached is:The equilibrium reached is:

36% αααα –D- glucose [αααα]D = + 18.7 0

64% ββββ –D- glucose [αααα]D = + 112 0

The sum is + 52.7o

Terms to remember Stereoisomers are isomeric

molecules that have the same molecular formula

and sequence of bonded atoms (constitution),

but which differ only in the three-dimensionalbut which differ only in the three-dimensional

orientations of their atoms in space.

In stereoisomers, the order and bond

connections of the constituent atoms remains

the same, but their orientation in space differ.

Enantiomers Are two stereoisomers

that are related to each other by a reflection:

they are mirror images of each other, which are

non-superimposable.

Human hands are a macroscopic example of

stereoisomerismstereoisomerism

For this reason, pure enantiomers exhibit the

phenomenon of optical activity .

Enantiomers• Optical isomers rotate the beam of

plane-polarized light for the same

angle, but in opposite direction

• Equimolar mixture of optical• Equimolar mixture of optical

isomers has no optical activity -

racemic mixture

• Glucose and Galactose are different from each other in the

stereochemistry of carbon 4. They are described as “Epimers”.• Glucose and Mannose are different from each other in the

stereochemistry of carbon 2. They are described as “Epimers”.

The term chiral is used to describe an object that is

non-superposable on its mirror image.

AchiralAchiral (not chiral) objects are objects that are

identical to their mirror image.

• Galactose and Mannose are different from each other in the

stereochemistry of carbons 2 and 4. They are described as

“Diastereoisomers””Diastereomers”.

Diastereomers:

CHO

CH OH

CHO

CHHOCHCHCH

CHCH2OH

OH

HOOH

D-Galactose

HO

CH

CH

CH

CH

CH2OH

OH

OH

HO

HO

D- Mannose

• Galactose and Mannose are different from each other in the

stereochemistry of carbons 2 and 4. They are described as

“Diastereoisomers””Diastereomers”.

Diastereomers:

CHO

CHCHHO

OHCHO

CH

CHHO

HOCHCHCHCH2OH

OH

HO

D-Galactose

HOCH

CH

CH

CH2OH

OH

OH

HO

D- Mannose

• Glucose and Fructose have the same molecular formula

C6H12O6. They have different structures with different

function groups. They are described as “Structural

Isomers”.

CHO CH OH

Structural isomers:

CHO

CH

CH

CH

CH

CH2OH

OH

OH

HO

OH

CH2OH

C

CH

CH

CH

CH2OH

OH

OH

HO

O

D-Glucose D-Fructose

Sugar derivatives

CH2OH

C

C

C

H OH

H OH

H OH

COOH

C

C

C

C

H OH

HO H

H OH

OHH

CHO

C

C

C

C

H OH

HO H

H OH

OHH

� 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

D-ribitol

C

D-gluconic acid D-glucuronic acid

CH2OH

OHH C

COOH

OHH

Sugar derivatives

H O

OH

H

OH

H

NHH

OH

CH2OH

HH O

OH

H

OH

H

NH

OH

CH2OH

H

C CH

O

amino sugar - an amino group substitutes for a hydroxyl.

An example is glucosamine.

The amino group may be acetylated, as in N-

acetylglucosamine.

NH2H

α-D-glucosamine

NH

α-D-N-acetylglucosamine

C CH3

H

NH O

H

COO−

OH

H

HOH

H

H

RCH3C

O

HC

HC

CH2OH

OH

OH

N-acetylneuraminate (sialic acid)

R =

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.

Glycosidic Bonds

The anomeric hydroxyl and a hydroxyl of another sugar

or some other compound can join together, splitting out

water to form a glycosidic bond:

R-OH + HO-R' ���� R-O-R' + H2OE.g., methanol reacts with the anomeric OH on glucose

to form methyl glucoside (methyl-glucopyranose).to form methyl glucoside (methyl-glucopyranose).

O

H

HO

H

HO

H

OH

OHHH

OH

α-D-glucopyranose

O

H

HO

H

HO

H

OCH3

OHHH

OH

methyl-α-D-glucopyranose

CH3-OH+

methanol

H2O

H O

OH

H

OHH

OH

CH2OH

H

O H

OH

H

OHH

OH

CH2OH

H

O

HH

1

23

5

4

6

1

23

4

5

6

maltose

H O

CH2OH

HO OH

CH2OH

HH

5

6

5

6

Disaccharides:

Maltose, a cleavage

product of starch

(e.g., amylose), is a

disaccharide with an

α(1→ 4) glycosidic

link between C1 - C4

OH of 2 glucoses.

Cellobiose, a product of cellulose breakdown, is the otherwise

equivalent ββββ anomer (O on C1 points up).

The β(1→ 4) glycosidic linkage is represented as a zig-zag, but

one glucose is actually flipped over relative to the other.

OH

H

OHH

OHH

H

H

OHH

OHH

H

O1

23

4 1

23

4

cellobiose

OH of 2 glucoses.

It is the αααα anomer

(C1 O points down).

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 α (O points down from ring), the linkage is α(1→2).

The full name of sucrose is α-D-glucopyranosyl-(1→2)-β-

D-fructopyranose.)

� Lactose, milk sugar, is composed of galactose & glucose,

with β(1→4) linkage from the anomeric OH of galactose.

Its full name is β-D-galactopyranosyl-(1→ 4)-α-D-

glucopyranose

Sucrose

• α-D-glucopyranosido-β-D-fructofuranoside

• β-D-fructofuranosido-α-D-glucopyranoside

• also known as tablet sugar

• commercially obtained from sugar cane or sugar beet

• hydrolysis yield glucose and fructose (invert sugar) ( sucrose: +66.5o ; glucose +52.5o; fructose –92o)

• used pharmaceutically to make syrups, troches

Sugar caneSugar cane

Sugar beet

Sucralfate (Carafate)

Lactose

• β-D-galactose joined to α−D-glucose via β (1,4) linkage

• milk contains the a and b-anomers in a 2:3 ratio

• β-lactose is sweeter and more soluble than ordinary α- lactoseα- lactose

• used in infant formulations, medium for penicillin production.

Maltose

• 2-glucose molecules joined via α(1,4) linkage

• known as malt sugar

• produced by the partial hydrolysis of starch (either

salivary amylase or pancreatic amylase)salivary amylase or pancreatic amylase)

• used as a nutrient (malt extract; Hordeum vulgare);

as a sweetener and as a fermentative reagent

Lactulose

• galactose-β-(1,4)-fructose

• a semi-synthetic disaccharide (not naturally occurring)

• not absorbed in the GI tract• not absorbed in the GI tract

• used either as a laxative (Chronulac) or in the management of portal systemic encephalopathy (Cephulac)

• metabolized in distal ileum and colon by bacteria to lactic acid, formic acid and acetic acid (remove ammonia)

Polysaccharides:

Plants store glucose as amylose or amylopectin, glucose

polymers collectively called starch.

H O

OH

H

OHH

OH

CH2OH

HO H

H

OHH

OH

CH2OH

H

O

HH H O

OH

OHH

OH

CH2OH

HH H O

H

OHH

OH

CH2OH

H

OH

HH O

OH

OHH

OH

CH2OH

H

O

H

1

6

5

4

3

1

2

amylose

polymers collectively called starch.

Glucose storage in polymeric form minimizes osmotic

effects.

Amylose is a glucose polymer with αααα(1→→→→4) linkages.

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

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

Amylopectin is a glucose polymer with mainly α(1→4)

linkages, but it also has branches formed by α(1→6)

linkages. Branches are generally longer than shown above.

The branches produce a compact structure & provide

multiple chain ends at which enzymatic cleavage can occur.

OHH OHH OHH OHHOHH

Glycogen, the glucose storage polymer in animals, is

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

glycogen

Glycogen, the glucose storage polymer in animals, is similar in structure to amylopectin.

But glycogen has more α(1→6) branches.

The highly branched structure permits rapid glucose release from glycogen stores, e.g., in muscle during exercise.

The ability to rapidly mobilize glucose is more essential to animals than to plants.

Cellulose, a major constituent of plant cell walls, consists

of long linear chains of glucose with β(1→4) linkages.

Every other glucose is flipped over, due to β linkages.

This promotes intra-chain and inter-chain H-bonds and

cellulose

H O

OH

H

OHH

OH

CH2OH

HO

H

OHH

OH

CH2OH

HO

H H O

O H

OHH

OH

CH2OH

HH O

H

OHH

OH

CH2OH

H

H

OHH O

O H

OHH

OH

CH2OH

HO

H H H H

1

6

5

4

3

1

2

This promotes intra-chain and inter-chain H-bonds and

van der Waals interactions,

that cause cellulose chains to

be straight & rigid, and pack

with a crystalline

arrangement in thick bundles

- microfibrils.

Schematic of arrangement of cellulose chains in a microfibril.

•Multisubunit Cellulose Synthase complexes in the

plasma membrane spin out from the cell surface

microfibrils consisting of 36 parallel, interacting cellulose

cellulose

H O

OH

H

OHH

OH

CH2OH

HO

H

OHH

OH

CH2OH

HO

H H O

O H

OHH

OH

CH2OH

HH O

H

OHH

OH

CH2OH

H

H

OHH O

O H

OHH

OH

CH2OH

HO

H H H H

1

6

5

4

3

1

2

microfibrils consisting of 36 parallel, interacting cellulose

chains.

•These microfibrils are very strong.

•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.

Polysaccharides or glycans

• homoglycans (starch, cellulose, glycogen, inulin)

• heteroglycans (gums, mucopolysaccharides)

• characteristics:• polymers (MW from 200,000)• polymers (MW from 200,000)

• White and amorphous products (glassy)

• not sweet

• not reducing; do not give the typical aldose or ketose reactions)

• form colloidal solutions or suspensions

Starch• most common storage polysaccharide in

plants

• composed of 10 – 30% α−amylose and 70-90% amylopectin depending on the source

• the chains are of varying length, havingmolecular weights from several thousands tohalf a million.

Amylose and amylopectin are the 2 forms of starch. Amylopectin

is a highly branched structure, with branches occurring every 12

to 30 residues

suspensions of amylose

in water adopt a helical

conformation

iodine (I2) can insert in

the middle of the amylose

helix to give a blue colorhelix to give a blue color

that is characteristic and

diagnostic for starch

(in starch)

(in cellulose)

Cellulose

• Polymer of β-D-glucose attached by β(1,4) linkages

• Yields glucose upon complete hydrolysis

• Partial hydrolysis yields cellobiose

• Most abundant of all carbohydrates• Cotton flax: 97-99% cellulose

• Wood: ~ 50% cellulose

• Gives no color with iodine

• Held together with lignin in woody plant tissues

Structure of cellulose

Linear structures of cellulose and chitin

(2 most abundant polysaccharides)

Products obtained from cellulose

• Microcrystalline cellulose : used as binder-disintegrant in tablets

• Methylcellulose: suspending agent and bulk laxative

• Oxidized cellulose: hemostat

• Sodium carboxymethyl cellulose: laxative• Sodium carboxymethyl cellulose: laxative

• Cellulose acetate: rayon; photographic film; plastics

• Cellulose acetate phthalate: enteric coating

• Nitrocellulose: explosives; collodion (pyroxylin)

Glycogen

• also known as animal starch

• stored in muscle and liver

• present in cells as granules (high MW)

• contains both α(1,4) links and α(1,6) branches at every 8 to 12 glucose unitevery 8 to 12 glucose unit

• complete hydrolysis yields glucose

• glycogen and iodine gives a red-violet color

• hydrolyzed by both α and β-amylases and by glycogen phosphorylase

Inulin

• β-(1,2) linked fructofuranoses

• linear only; no branching

• lower molecular weight than starch

• colors yellow with iodine

Jerusalem artichokes

• hydrolysis yields fructose

• sources include onions, garlic, dandelions and jerusalem artichokes

• used as diagnostic agent for the evaluation of glomerular filtration rate (renal function test)

Chitin

• chitin is the second most abundant

carbohydrate polymercarbohydrate polymer

• present in the cell wall of fungi and in the

exoskeletons of crustaceans, insects and

spiders

• chitin is used commercially in coatings

(extends the shelf life of fruits and meats)

Chitin

• Chitin is the second most

abundant carbohydrate

polymer

• Present in the cell wall of • Present in the cell wall of

fungi and in the

exoskeletons of

crustaceans, insects and

spiders

• Chitin is used

commercially in coatings

(extends the shelf life of

fruits and meats)

Dextrans

• products of the reaction of glucose and the enzyme transglucosidase from Leuconostoc mesenteroides

• contains α (1,4), α (1,6) and α (1,3) linkages

• MW: 40,000; 70,000; 75,000• MW: 40,000; 70,000; 75,000

• used as plasma extenders (treatment of shock)

• also used as molecular sieves to separate proteins and other large molecules (gel filtration chromatography)

• components of dental plaques

Dextrins

• produced by the partial hydrolysis of starch along with maltose and glucose

• dextrins are often referred to as either amylodextrins, erythrodextrins or amylodextrins, erythrodextrins or achrodextrins

• used as mucilages (glues)

• also used in infant formulas (prevent the curdling of milk in baby’s stomach)

Glycosaminoglycans

• they are the polysaccharide chains of proteoglycans

• they are linked to the protein core via a serine or

threonine (O-linked)

• the chains are linear (unbranched)• the chains are linear (unbranched)

• the glycosaminoglycan chains are long (over 100

monosaccharides)

• they are composed of repeating disaccharides

Glycosaminoglycans

Involved in a variety of extracellular functions; chondroitin

is found in tendons, cartilage and other connective tissues

Glycosaminoglycans

A characteristic of glycosaminoglycans is the presence

of acidic functionalities (carboxylate and/or sulfates)

Hyaluronic acid derivatives

• several products are used in the management

of osteoarthritis symptoms

– Hyalagan and Synvisc

• others are used as ophthalmic surgical • others are used as ophthalmic surgical

adjuncts in cataract extractions, intraocular

lens implantation, corneal transplant and

retinal attachment surgery (Healon, Amvisc,

AMO Vitrax)

Glycosaminoglycans

Gums

• widely used in the food and pharmaceutical industry

• used as: suspending agents, gelling agents,

thickening agents, emulsifiers, foam stabilizers,

crystallization inhibitors, adhesives, binding agents

• agar, tragacanth, karaya, carrageenan, guar gum,

gum arabic (acacia), furcellaran, sodium alginate,

locust bean gum

Gum tragacanth

Structure of

peptidoglycan

Cell wall of Gram-positive bacteria

Cross-section of the cell

wall of a gram-negative

organism such as E.coli

Lipopolysaccharide (LPS) coats the

outer membrane of Gram-negative

bacteria.

the lipid portion of the LPS is embedded

in the outer membrane and is linked to

a complex polysaccharide

Teichoic acids are covalently linked to the peptidoglycan of gram-positive

bacteria. These polymers of glycerol phosphate (a and b) or ribitol phosphate (c)

are linked by phosphodiester bonds

Mycobacterial cell wall

H O

H

H

OHH

OH

COO−

H

H O

OH H

H

NHCOCH3H

CH2OH

H

OO

D-glucuronate

O

1

23

4

5

61

23

4

5

6

N-acetyl-D-glucosamine

hyaluronate

Glycosaminoglycans (mucopolysaccharides) are linear

polymers of repeating disaccharides.

The constituent monosaccharides tend to be modified,

with acidic groups, amino groups, sulfated hydroxyl and

amino groups, etc.

Glycosaminoglycans tend to be negatively charged,

because of the prevalence of acidic groups.

H O

H

H

OHH

OH

COO−

H

H O

OH H

H

NHCOCH3H

CH2OH

H

OO

D-glucuronate

O

1

23

4

5

61

23

4

5

6

N-acetyl-D-glucosamine

Hyaluronate (hyaluronan) is a glycosaminoglycan with a

repeating disaccharide consisting of 2 glucose derivatives,

glucuronate (glucuronic acid) & N-acetyl-glucosamine.

The glycosidic linkages are β(1→3) & β(1→4).

N-acetyl- -glucosamine

hyaluronate

heparan sulfate glycosaminoglycan

cytosol

core protein

transmembrane α-helix

Extracellular

Matrix Material

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.

Some proteoglycans of the extracellular matrix bind non-covalently to hyaluronate via protein domains called linkmodules. E.g.:

• Multiple copies of the “aggrecan proteoglycan” associatewith hyaluronate in cartilage to form large complexes.

• Versican, another proteoglycan, binds hyaluronate in theextracellular matrix of loose connective tissues. (mucousconnective tissue, reticular connective tissue and adipose tissue)

CH OH

H O

H

H

OHH

OH

COO−

H

H O

OH H

H

NHCOCH3H

CH2OH

H

OO

D-glucuronate

O

1

23

4

5

61

23

4

5

6

N-acetyl-D-glucosamine

hyaluronate

H O

H

OSO3−H

OH

H

COO−O H

H

NHSO3−H

OH

CH2OSO3−

H

H

H

O

O

heparin or heparan sulfate - examples of residues

iduronate-2-sulfate N-sulfo-glucosamine-6-sulfate

Heparan sulfate is initially synthesized on a membrane-embedded core protein as a polymer of alternatingN-acetylglucosamine and glucuronate residues.

Later, in segments of the polymer, glucuronate residuesmay be converted to the sulfated sugar iduronic acid,while N-acetylglucosamine residues may be deacetylated

and/or sulfated. Have ANTI.VIRAL Activity.

Heparin, a soluble glycosaminoglycan

found in granules of mast cells, has a

structure similar to that of heparan

sulfates, but is more highly sulfated.

When released into the blood, it

inhibits clot formation by interacting

with the protein anti-thrombin.

PDB 1RID

with the protein anti-thrombin.

Heparin has an extended helical

conformation.

heparin: (IDS-SGN)5

C O N S

The core protein of a syndecan heparan sulfate

heparan sulfate glycosaminoglycan

cytosol

core protein

transmembrane α-helix

Some cell surface heparan

sulfate glycosaminoglycans

remain covalently linked to

core proteins embedded in

the plasma membrane.

� The core protein of a syndecan heparan sulfateproteoglycan includes a single transmembrane αααα-helix,as in the simplified diagram above.

� The core protein of a glypican heparan sulfateproteoglycan is attached to the outer surface of theplasma membrane via covalent linkage to a modifiedphosphatidylinositol lipid.

Proteins involved in signaling & adhesion at the cell

surface recognize & bind heparan sulfate chains.

E.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 groups at particular locations on heparan sulfate chains

to alter affinity

for signal

proteins, e.g.,

growth factors.

H O

H

OSO3−H

OH

H

COO−O H

H

NHSO3−H

OH

CH2OSO3−

H

H

H

O

O

heparin or heparan sulfate - examples of residues

iduronate-2-sulfate N-sulfo-glucosamine-6-sulfate

Figure 3.5 Some of the polysaccharides in plants and animals

H O

OH

O

H

HNH

OH

CH2OH

H

C CH3

O

β-D-N-acetylglucosamine

CH2 CH

C

NH

O

H

serine residue

Oligosacch

arides that are

covalently attached

to proteins or to

membrane lipids

may be linear or

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.

may be linear or

branched chains.

Oligosaccharides

• Trisaccharide: raffinose (glucose, galactose and fructose)

• Tetrasaccharide: stachyose (2 galactoses, glucose and fructose)glucose and fructose)

• Pentasaccharide: verbascose (3 galactoses, glucose and fructose)

• Hexasaccharide: ajugose (4 galactoses, glucose and fructose)

Honey also contains glucose and fructose along with

some volatile oils

starch

Structures of some oligosaccharides

Structures of some oligosaccharides

Structures of some oligosaccharides

An enzymatic product (Beano) can be used to prevent

the flatulence

Oligosaccharides occur widely as components of

antibiotics derived from various sources

H O

OH

O

H

HNH

OH

CH2OH

H

C CH3

O

β-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).

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

R

Asn

X

Ser or ThrN-acetylglucosamine

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.

HC

C

R

O

Ser or ThrInitial sugar in N-linked glycoprotein oligosaccharide

Lectins are glycoproteins that recognize and bind to specific

oligosaccharides.

Concanavalin A & wheat germ agglutinin are plant lectins

that have been useful research tools.

The C-type lectin-like domain is a Ca++-binding

carbohydrate recognition domain in many animal lectins.

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.

Examples of animal lectins:

Mannan-binding lectin (MBL) is a glycoprotein found in

blood plasma.

It binds cell surface carbohydrates of disease-causing

microorganisms & promotes phagocytosis of these

organisms as part of the immune response. organisms as part of the immune response.