Carbohydrates-structure and function

General Biochemistry-II(BCH 302)

Dr . Saba Abdi

Asst . Prof. Dept. Of Biochemistry

College Of Science

King Saud University. Riyadh.KSA

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Importance of the topicWhy is this topic important?

•All organisms utilize carbohydrates important biomolecules

•Nutrition: “carbos” are more than just starch and sugar

•Application of previous concepts:functional groupsstereochemistry

other structural features} control biological properties

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Origin of “Carbohydrate”Before 1900

} Monosaccharide: cannot behydrolyzed into simpler sugars

Glucose C6H12O6

Fructose C6H12O6 no changeH2O, H3O+

no changeH2O, H3O+

Hydrolysis: “water breaking;” reaction with water, often in the presence of acid or base

Sucrose C12H22O11H2O, H3O+

glucose + fructose

Cellulose CnH2nOn

H2O, H3O+

many glucose

Disaccharide: saccharide composed of two simpler sugars

Polysaccharide: composedof many monosaccharides}

Starch CnH2nOnH2O, H3O+

many glucose

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QuickTime™ and aDV/DVCPRO - NTSC decompressor

are needed to see this picture.

Origin of “Carbohydrate”Sugar general formula = CnH2nOn

Confirmationsucrose + H2SO4 C + H2O (steam)

dehydrating agent

= Cn(H2O)n

= carbohydrate= “carbon hydrate”

sucrose

H2SO4steam

carbon

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Carbohydrates• Widely distributed in nature

• Function

– Structural

– Source of energy

– Storage of energy

• Chemical structure

– Polyhydroxyaldehydes - aldoses

– Polyhydroxyketones - ketoses

• Classification

– monosaccharides (1 unit)

– oligosaccharides (2-10 units)

– polysaccharides (> 10 units)

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Monosaccharides-molecular structure• Chemical structure

– Polyhydroxyaldehydes - aldoses– Polyhydroxyketones - ketoses

Number of carbon atoms trioses (C-3) tetroses (C-4) pentoses (C-5) hexoses (C-6) heptoses (C-7)

Contain asymmetric carbon atoms C* => optically active

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

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C HHO

C OHH

C OHH

CH2OH

CH2OH

C O

D-fructose

C

C OHH

C HHO

C OHH

C OHH

CH2OH

D-glucose

OH

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Enantiomers• Mirror image isomers are called enantiomers.• There are two series: D- and L-.• In the D isomeric form, the OH group on the asymmetric

carbon (a carbon linked to four different atoms or groups) farthest from the carbonyl carbon is on the right.

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).

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Levorotation and dextrorotation• Optical isomers rotate the beam of plane-

polarized light for the same angle, but in opposite direction.

• Equimolar mixture of optical isomers has no optical activity - racemic mixture

Dextrorotation and levorotation refer, respectively, to the properties of rotating plane polarized light clockwise (for dextrorotation) or counterclockwise (for levorotation).

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• A compound with dextrorotation is called dextrorotatory or dextrorotary ,while a compound with levorotation is called levorotatory or levorotary

• Both D- and L- isomers can be dextrotatory or leavorotatory. A dextrorotary compound is often prefixed "(+)-" or "d-". Likewise, a levorotary compound is often prefixed "(–)-" or "l-".

• These "d-" and "l-" prefixes should not be confused with the "D-" and "L-" prefixes which is based on the actual configuration of each enantiomer, with the version synthesized from naturally occurring (+)-glyceraldehyde being considered the D- form

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The (D)-Aldose FamilyThe (D)-Aldotrioses

C

C

CH2OH

HO H

H O

C

C

CH2OH

H OH

H O

One stereocenter two enantiomers

(L)-(-)-glyceraldehyde (D)-(+)-glyceraldehyde

C

C

CH2OH

H OH

H O

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Alternate representation

C

C

CH2OH

H OH

H O

The (D)-Aldose FamilyFischer Projections

Emil Fischer•Determined relative structure of (D)-aldoses•Nobel Prize in Chemistry 1902•Most natulral saccharides are (D)-form

(D)-(+)-glyceraldehyde

C

C

CH2OH

H OH

H O

Vertical lines= broken wedges

Horizontal lines= solid wedges

Fischer projection

CHO

H OH

CH2OH

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The (D)-Aldose FamilyThe (D)-Aldotetroses

Two stereocenters four stereoisomers Two (D) and two (L)

(D)-(-)-erythrose (D)-(-)-threoseNot found in nature

C

C

CH2OH

H OH

COH

H OH C

C

CH2OH

H OH

COH

HO H

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The (D)-Aldose FamilyThe (D)-Aldopentoses

Three stereocenters eight stereoisomers Four (D) and four (L)

(D)-(-)-riboseRNA (ribonucleic acid)

DNA (deoxyribonucleic acid)

(D)-(-)arabinose (D)-(-)-lyxoseNot found in nature

(D)-(+)-xyloseC

C

CH2OH

H OH

H OH

CH

C

OH

OH

C

C

CH2OH

H OH

H OH

CHO

C

H

OH

C

C

CH2OH

H OH

HO H

CH

C

OH

OH

C

C

CH2OH

H OH

HO H

CHO

C

H

OH

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The (D)-Aldose FamilyThe (D)-Aldohexoses

Four stereocenters 16 stereoisomers eight (D) and eight (L)

(D)-(+)-allosenot found in nature

C

C

CH2OH

H OH

H OH

CH OH

CH OH

COH

(D)-(+)-altrose

C

C

CH2OH

H OH

H OH

CH OH

CHO H

COH

(D)-(+)-glucosemost abundant

monosaccharide

C

C

CH2OH

H OH

H OH

CHO H

CH OH

COH

(D)-(+)-mannose

C

C

CH2OH

H OH

H OH

CHO H

CHO H

COH

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The (D)-Aldose FamilyThe (D)-Aldohexoses

Four stereocenters 16 stereoisomers eight (D) and eight (L)

(D)-(-)-gulosenot found in nature

C

C

CH2OH

H OH

HO H

CH OH

CH OH

COH

(D)-(-)-idose

C

C

CH2OH

H OH

HO H

CH OH

CHO H

COH

(D)-(+)-galactosefairly common

C

C

CH2OH

H OH

HO H

CHO H

CH OH

COH

(D)-(+)-talose

C

C

CH2OH

H OH

HO H

CHO H

CHO H

COH

•Most important aldoses: glucose, ribose, galactose

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Epimers

• Pairs of monosaccharides different only in configuration around only one specific C-atom.

• For example, glucose and galactose are C-4 epimers—their structures differ only in the position of the -OH group at carbon 4.

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Cyclization of monosaccharides

• monosaccharides with five or more carbons are predominantly found in a ring (cyclic) form, in which the aldehyde (or ketone) group has reacted with an alcohol group on the same sugar

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O C

H

R

OH

O C

R

R'

OHC

R

R'

O

aldehyde alcohol hemiacetal

ketone alcohol hemiketal

C

H

R

O R'R' OH

"R OH "R

+

+

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Cyclic Structures

• most stable are rings with 5 and 6 members

• most common in nature

• in accordance to oxygen containing heterocycles monosaccharides are called

• with 5 atoms in cycle furan• with 6 atoms in cycle pyranoses

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O

O

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Cyclic Structures

• Glucose forms an intra-molecular hemiacetal, as the C1 aldehyde & C5 OH react, to form a 6-member pyranose ring, named after pyran

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H O

OH

H

OHH

OH

CH2OH

H

OH

H H O

OH

H

OHH

OH

CH2OH

H

H

OH

-D-glucose -D-glucose

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4

5

6

1 1

6

5

4

3 2

H

CHO

C OH

C HHO

C OHH

C OHH

CH2OH

1

5

2

3

4

6

D-glucose (linear form)

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Cyclic Structures

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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

D-fructose (linear) -D-fructofuranose

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. This ring is more stable for all ketones.

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Cyclization of glucose produces a new asymmetric center at C1 (in frucose at C2) . The 2 stereoisomers are called anomers, & .

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 and anomers of D-glucose interconvert in aqueous solution by a process called mutarotation.

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H O

OH

H

OHH

OH

CH2OH

H

-D-glucose

OH

H H O

OH

H

OHH

OH

CH2OH

H

H

OH

-D-glucose

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4

5

6

1 1

6

5

4

3 2

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• Because of the tetrahedral nature of carbon bonds, pyranose sugars actually assume a "chair" or "boat" configuration, depending on the sugar.

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O

H

HO

H

HO

H

OH

OHHH

OH

O

H

HO

H

HO

H

H

OHHOH

OH

-D-glucopyranose -D-glucopyranose

1

6

5

4

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Reducing sugars• If the oxygen on the anomeric carbon of a sugar

is not attached to any other structure, that sugar can act as a reducing agent and is termed a reducing sugar. Such sugars can react with chromogenic agents (for example, Benedict's reagent or Fehling's solution) causing the reagent to be reduced and colored, with the anomeric carbon of the sugar becoming oxidized to a carboxyl group.

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Reactions of monosaccharides*• 1. Esterification

• 2.Oxidation (only aldose sugar)

• 3. Reduction

• 4. Cyanohydrin

• 5.Osazone (test for identification of sugar)

• 6. Furfurals

• 7. Enolization

(* Refer to hand out of reactions)

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Sugar derivative

sugar alcohol – Formed by reduction of an aldehyde or ketone group of monosaccharide; 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, ascorbic acid (vitamin C).

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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

CH2OH

C

C

C

CH2OH

H OH

H OH

H OH

D-ribitolDr.Saba

amino sugar –

an amino group substitutes for a hydroxyl. An example is glucosamine (component of chitin). The amino group may be acetylated, as in N-acetylglucosamine.

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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

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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.

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NH O

H

COO

OH

H

HOH

H

H

RCH3C

O

HC

HC

CH2OH

OH

OH

N-acetylneuraminate (sialic acid)

R =

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Glycosidic BondsThe 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' + H2O

E.g., methanol reacts with the anomeric OH on glucose to form methyl glucoside (methyl-glucopyranose).

Glycosidic bonds are readily hydrolyzed by acid but resist cleavage by base

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O

H

HO

H

HO

H

OH

OHHH

OH

-D-glucopyranose

O

H

HO

H

HO

H

OCH3

OHHH

OH

methyl- -D-glucopyranose

CH 3-O H+

methanol

H2O

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O- and N-glycosides

• If the group on the non-carbohydrate molecule to which sugar is attached is -OH group the structure is an O-glycoside.

• If the group is an-NH2, the structure is N-glycoside

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Disaccharides•Composed of two monosaccharide molecules

•Useful vocabulary:

Linked by glycoside (an ether), part of acetal functional group

Other anomeric carbon = hemiacetal functional group

glycoside linkageC-O-C

OO

O

CH2OH

HO

HOHO

HOHO

CH2OH

OH

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DisaccharidesCarbohydrate Ring Numbering

•Anomeric carbon receives lowest number

•Carbon 1 in aldoses

•Carbon 2 (rarely 3) in ketoses

•All other carbons numbered in order

OO

CH2OH

HO

HO1

2

3

4 5

6

O

Numbering for an aldohexose

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Naming disaccharides• By convention the name describes the compound with its

nonreducing end to the left, and we can “build up” the name in the following order.

• (1) Give the configuration (or β) at the anomeric carbon joining the first monosaccharide unit (on the left) to the second.

• (2) Name the nonreducing residue; to distinguish five- and six-membered ring structures, insert “furano” or “pyrano” into the name.

• (3) Indicate in parentheses the two carbon atoms joined by the glycosidic bond, with an arrow connecting the two numbers

• (4) Name the second residue

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DisaccharidesLactose

1,4’--D-galactopyranosyl-D-glucopyranose

•Present in mammalian milk (up to 8 % by weight; varies with species)

•Readily digested by infant mammals; requires enzyme lactase

•Adults often less tolerant due to low levels of lactase

•It is a reducing sugar

Lactose

OO

O

CH2OHHO

HO

OH

HO

CH2OH

OHHOH3O+/H2O

hydrolysis

+O

OH

CH2OH

HOHO

HO

Glucopyranose(glucose)

Galactopyranose(galactose)

OCH2OH

HO

HO

HO OH

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DisaccharidesSucrose

1,2’--D-fructofuranosyl--D-glucopyranose

•Unusual structure: 1,2’--glycoside

•Most common disaccharide in nature

•Produced only by plants such as sugar cane, sugar beats

•An -glycoside: readily digested by mammalsSucrose contains no free anomeric carbon atom; the anomeric carbons of both monosaccharide units are involved in the glycosidic bond . Sucrose is therefore a nonreducing sugar.

Sucrose

O

O O

CH2OH

HOHO

HO

OH

OH

CH2OH

CH2OH

H3O+/H2O

hydrolysis

O

OH

CH2OH

HOHO

HO

Glucopyranose(glucose)

Fructofuranose(fructose)

+ O

OH

OH

CH2OHHO

CH2OH

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• 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.

• Because the disaccharide retains a free anomeric carbon (C-1 of the glucose residue on the right) , maltose is a reducing sugar

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H O

O H

H

O HH

O H

CH 2O H

H

O H

O H

H

O HH

O H

CH 2O H

H

O

HH

1

23

5

4

6

1

23

4

5

6

m altose

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Cellobiose, a product of cellulose breakdown,

The (1 4) glycosidic linkage between two glucose molecules.

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H O

O H

H

O HH

O H

CH 2O H

H

O O H

H

H

O HH

O H

CH 2O H

H

H

H

O1

23

4

5

6

1

23

4

5

6

cellobiose

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• Trehalose is found in plants and insects

• formed by an α,α-1,1-glucoside bond between two α-glucose units

• It is non reducing sugar

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Polysaccharides

• Generally called glycans• Contains a number of monosaccharide units linked

by glycosidic bonds• Divided into two broad groups:

(i)Homopolysaccharides-contains only one type of monomer. Examples:Starch,cellulose,glycogen

(ii)Heteropolysaccharides- Contain two or more types of monomers. Examples: hyaluronic acid, chondriotin sulphate, heparin, and mureins.

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PolysaccharidesCellulose

•Linear 1,4--D-glucopyranose polymer

•~5,000 - 10,000 glucopyranose molecules per cellulose molecule

repeating subunit:glucopyranose

OO

OO

OOO

HO

CH2OH

OHHO

CH2OH

OH

CH2OH

HOOH

•Most abundant organic substance in nature

•Function: support structure in plants

Wood is ~50% cellulose by weight

Strength due to intermolecular hydrogen bonding

H3O+/H2O

hydrolysis

O

OH

CH2OH

HOHO

HO

Many glucopyranose

•Not easily digested by mammals Dr.Saba

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

Every other glucose is flipped over, due to linkages.

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

Multisubunit Cellulose Synthase complexes in the plasma membrane spin out from the cell surface 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.

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Chitin

• It is a structural homopolysaccharide

• It is a linear molecule composed of N-acetylglucosamine monomers linked by β (1→4) glycosidic bond

• It forms extended fibers similar to that of cellulose

• It is component of exoskeleton of insects

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Polysaccharides

OOHO

CH2OH

HO OOHO

CH2OH

HO O

O

OHO

CH2OH

HOAmylose

Starch•Two forms: amylose, amylopectin

Amylose•Linear coiled polymer of glucopyranose linked by α-1,4 glycosidic bonds•20-25% of starch OO

HO

CH2OH

HO OOHO

HO O

O

OHO

CH2OH

HO

O

O

OHO

CH2OH

HO

Amylopectin

Amylopectin•Branched polymer containing glucopyranose linked by α-1,4 glycosidic bonds. Branch points has α-1,6glycosidic bonds, 12 glucose in a branch• 75-80% of starch

•1,4’--D-glucopyranose polymer•Function: plant glucose/energy storage•Hydrolysis glucopyranose•Easily digested by mammals•Glucose storage in polymeric form minimizes osmotic effects

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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 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.

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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

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Glycosaminoglycans

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.

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Hyaluronate (hyaluronan) is a glycosaminoglycan with a repeating disaccharide consisting of 2 glucose derivatives, glucuronate (glucuronic acid) & N-acetyl-glucosamine. The glycosidic linkages are (13) & (14). Form ground substance of connective tissue.

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H O

H

H

O HH

O H

COO

H

H O

O H H

H

NH COCH 3H

CH 2O H

H

OO

D -g lucuronate

O

1

23

4

5

61

23

4

5

6

N -acetyl-D -g lucosam ine

hyaluronate

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.• Inulin :Plant polysaccharide of fructose residues

connected by 2-1 linkage• Chitin: Polymer of N-acetylglucosamine linked

through β-1,4 glycosidic bond. Found in fungal cell wall and arthropod cuticle

• Mannan: Polymer of mannose linked by α-1,4 and α-1,3 glycosidic bonds. Found in cell wall of bacteria yeast and some plants.

• Heparin: Consists of glucosamine N-sulphate and sulphate esters of glucuronic acid. Found in granules of mast cells has anticoagulant properties.

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Physical propreties of carbohydrates

• Monosaccharides are colorless crystalline solids, very soluble in water, but only slightly soluble in ethanol, low molecular weight, sweet tasting

• Disaccharides are low molecular weight, sweet,crystalline, less soluble in water than monosaccharides

• Polysaccharides are high molecular weight, not sweet, not soluble and not crystalline.

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Complex Carbohydrates

• Carbohydrates can be attached by glycosidic bonds to non-carbohydrate structures :

(a)Nitrogen bases (in nucleic acids)

(b)Aromatic ring (in steroid and bilirubin)

(c)Proteins (in glycoproteins and glucosaminoglycans)

(d) Lipids (in glycolipids)

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