0 carbohydrate chemistry 1

8/7/2019 0 Carbohydrate Chemistry 1

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DISUSUN OLEH

Dr.H.MOHAMMAD HANAFI, MBBS (Syd.).MS.

FAKULTAS KEDOKTERAN UNAIR


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Monosaccharides - simple sugars with multiple

OH groups. Based on number of carbons (3, 4,

5, 6), a monosaccharide is a triose, tetrose,

pentose orhexose.

Disaccharides - 2 monosaccharides covalentlylinked.

Oligosaccharides - a few monosaccharides

covalently linked. (4-10 carbon)

Polysaccharides - polymers consisting of chains

I(CH2O)n r H-C-OHI

Carbohydrates (glycans) have the following

basic composition:


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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


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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.

C

C

C

C

C

C

C

C

C

C

C

C

L- l ceralde de- l ceralde de

L- l ceralde de- l ceralde de


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Sugar Nomenclature

For sugars with more

than one chiral center,

D orL 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 HCH2OH CH2OH

D-glucose L-glucose


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D & L sugars are mirrorimages of one another.

They have the samename, 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 numberof asymmetric centers.

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

2 2

-glucose -glucose


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Hemiacetal & hemiketal

formation

An aldehyde

can react withan alcohol to

form a

hemiacetal.

A ketone can

react with an

alcohol to form

a hemiketal.

H

H

'

H

'

al ehy e alcohol hemiacetal

ketone alcohol hemiketal

H

'' H

" H "

+

+


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Pentoses andhexoses can

cyclize as theketone oraldehyde reactswith a distal OH.

Glucose forms anintra-molecularhemiacetal, asthe C1 aldehyde

& C5 OH react,to form a 6-memberpyranose ring,

named afterran.

These representations of the cyclic sugars are calle

Haworthprojections.

H O

OH

H

OHH

OH

CH OH

H

OH

H H O

OH

H

OHH

OH

CH OH

H

H

OH

E- -glucose F- -glucose

23

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

-glucose(linear orm)


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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.

CH2OH

C O

C HHO

C OHH

C OHH

CH2OH

HOH2C

OH

CH2OH

H

OHH

H HO

O

1

6

5

4

3

2

6

5

4 3

2

1

D-fructose (linear) E-D-fructofuranose


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Cyclization of glucose produces a new asymmetric

centerat C1. The 2 stereoisomers are called

anomers, E & F.Haworth projections represent the cyclic sugars as

having essentially planar rings, with the OH at the

anomeric C1:

E (OH below the ring)

H O

OH

H

OHH

OH

CH2OH

H

E- -glucose

OH

H HO

OH

H

OHH

OH

CH2OH

H

H

OH

F- -glucose

23

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.

The representation above reflects the chair

configuration of the glucopyranose ring more

accurately than the Haworth projection.

O

H

HO

H

HO

H

OH

OHHH

OH

O

H

HO

H

HO

H

H

OHHOH

OH

E-D-glucopyranose F-D-glucopyranose

1

6

5

4

32


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Sugar derivatives

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

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

CH2OH

OHH

CHO

C

C

C

C

H OH

HO H

H OH

COOH

OHH


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Sugar derivatives

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

The amino group may be acetylated, as inN-acetylglucosamine.

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N-acetylneuraminate (N-acetylneuraminic acid,also called sialic acid) is often found as a terminal

residue of oligosaccharide chains ofglycoproteins.

Sialic acid imparts negative charge toglycoproteins, because its carboxyl group tends to

dissociate a proton at physiological pH, as shown

NH O

H

COO

OH

H

HOH

H

H

R

CH3C

O

HC

HC

CH2OH

OH

OH

N-acetylneuraminate (sialic aci )

R =


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

The F(1p 4) glycosidic linkage is represented as a

zig-zag, but one glucose is actually flippedover

HO

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

OH

H

OHH

OH

CH2OH

HO OH

H

H

OHH

OH

CH2OH

H

H

H

O1

23

4

5

6

1

23

4

5

6

cellobiose

Disaccharides:

Maltose, a cleavagepro uct of starch(e.g., amylose), is a

isacchari e with anE(1p 4) glycosi ic

link between C1 - C4OH of 2 glucoses.

It is the E anomer(C1 O points own).


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Otherdisaccharides include:

Sucrose, common table sugar, has a glycosidicbond linking the anomeric hydroxyls ofglucose &

fructose.

Because the configuration at the anomeric C of

glucose is E (O points down from ring), the linkageis E(1p2).

The full name of sucrose is E-D-glucopyranosyl-(1p2)-F-D-fructopyranose.)

Lactose, milk sugar, is composed ofgalactose &glucose, with F(1p4) linkage from the anomericOH of galactose. Its full name is F-D-galactopyranosyl-(1p 4)-E-D-glucopyranose


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-D-galactopyranosyl-(1p 4)--D-glucopyranose


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Polysaccharides:

Plants store glucose as amylose oramylopectin,glucose polymers collectively called starch.

Glucose storage in polymeric form minimizesosmoticeffects.

Amylose is a glucose polymer with E(1p4) linkages.It adopts a helical conformation.

The end of the polysaccharide with an anomeric C1

not involved in a glycosidic bond is called thereducin end.

H O

OH

H

OHH

OH

CH2OH

H

O H

H

OHH

OH

CH2OH

H

O

HH H O

O

H

OHH

OH

CH2OH

HH H

O

H

OHH

OH

CH2OH

H

OH

HH O

O

H

OHH

OH

CH2OH

H

O

H

1

6

5

4

3

1

2

amylose


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Amylopectin is a glucose polymer with mainly E(1p4)

linkages, but it also has branches formed by E(1p6)

linkages. Branches are generally longer than shownabove.

The branches produce a compact structure & provide

multiple chain ends at which enzymatic cleavage can

H O

OH

H

OHH

OH

CH2OH

H

O H

H

OHH

OH

CH2OH

H

O

HH H O

O

H

OHH

OH

CH2

HH H O

H

OHH

OH

CH2OH

H

OH

HH O

O

H

OHH

OH

CH2OH

H

O

H

O

1 4

6

H O

H

OHH

OH

CH2OH

H

H H O

H

OHH

OH

CH2OH

H

H

O1

OH

3

4

5

2

amylopectin


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

But glycogen has more E(1p6) branches.

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

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

H O

OH

H

OHH

OH

CH2OH

H

O H

H

OHH

OH

CH 2OH

H

O

HH H O

O

H

OHH

OH

CH2

HH H O

H

OHH

OH

CH2OH

H

OH

HH O

O

H

OHH

OH

CH2OH

H

O

H

O

1 4

6

H O

H

OHH

OH

CH2OH

H

H H O

H

OHH

OH

CH2OH

H

H

O

1

OH

3

4

5

2

glycogen


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Cellulose, a major constituent ofplant cell walls,consists of long linear chains of glucose with

F(1p4) linkages.Everyotherglucoseisflippedover, due to Flinkages.

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

and

cellulose

H O

OH

H

OHH

OH

CH2OH

H

O

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

van der Waals interactions,that cause cellulose chains

to be straight & rigid, andpack with a crystallinearrangement in thickbundles - microfibrils.

See: Botany online

S h m ti of rr ng m nt of

llulos h ins in mi rofibril.


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Multisubunit CelluloseSynthase complexes in the

plasma membrane spin out from the cell surfacemicrofibrils 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.

cellulose

H O

OH

H

OHH

OH

CH2OH

H

O

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


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Glycosaminoglycans (mucopolysaccharides) are polymersofrepeatingdisaccharides.

The constituent monosaccharides tend to be modified, with

acidic groups, amino groups, sulfated hydroxyl and aminogroups, etc.

Glycosaminoglycans tend to be negativelycharged,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


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Hyaluronate (hyaluronan) is a glycosaminoglycan

with a repeating disaccharide consisting of 2 glucosederivatives, glucuronate (glucuronic acid) & N-acetyl-

glucosamine.

The glycosidic linkages are F(1p3) & F(1p4).

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-glucosaminehyaluronate


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Proteoglycans are glycosaminoglycans thatare covalently linked to serine residues of specificcoreproteins.

The glycosaminoglycan chain is synthesized bysequential addition of sugar residues to the core

protein.

heparan sulfateglycosaminoglycan

cytosol

coreprotein

transmembraneE-helix


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Someproteoglycans of the extracellular matrixbind non-covalently to hyaluronate via proteindomains called linkmodules. E.g.:

Multiple copies of the aggrecan proteoglycanassociate with hyaluronate in cartilage to formlarge complexes.

Versican, another proteoglycan, bindshyaluronate in the extracellular matrix of looseconnective tissues.

HO

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

Websites on:

Aggrecan

Aggrecan &versican.


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Heparansulfate 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 residues maybe converted to the sulfated sugariduronicacid, while N-acetylglucosamine residues may be deacetylated and/orsulfated.

H O

H

OSO3

H

OH

H

COO

O H

H

NHSO3H

OH

CH2OSO3

H

H

H

O

O

heparin or heparan sulfate - examples of resi ues

i uronate-2-sulfate N-sulfo-glucosamine-6-sulfate


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Heparin, a solubleglycosaminoglycan found in

granules of mast cells, has astructure similar to that of heparansulfates, but is more highlysulfated.

When released into the blood, itinhibits clot formation by interactingwith the protein antithrombin.

Heparin has an extendedhelicalconformation.

heparin: (I S-SGN)5

P B 1RI

C O N S

Chargerepulsion by the many negatively chargedgroups may contribute to this conformation.

Heparin shown has 10 residues, alternating IDS

(iduronate-2-sulfate) & SGN (N-sulfo-glucosamine-6-


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Some cell surface heparansulfateglycosaminoglycans remain covalently linked tocore proteins embedded in the plasma membrane.

Proteins involved in signaling & adhesion at thecell surface recognize and bind segments ofheparan sulfate chains having particular patternsof sulfation.

heparan sulfateglycosaminoglycan

cytosol

core

protein

transmembraneE-helix


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O-linkedoligosaccharide chains of glycoproteinsvary in complexity.

They link to a protein via a glycosidic bond betweena sugar residue & a serineorthreonine OH.

O-linked oligosaccharides have roles inrecognition, interaction, and enzymeregulation.

H

H

H

HNH

H

CH2 H

H

C CH3

F- -N-acetylglucosami e

CH2 CH

C

NH

H

seri eresidue

Oligosaccharidesthat are covalently

attached toproteins or tomembrane lipidsmay be linear orbranched chains.


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H O

OH

O

H

HNH

OH

CH2OH

H

C CH3

O

F-D-N

-acetylglucosa ine

CH2 CH

C

NH

O

H

serineresi ue

N-acetylglucosamine (GlcNAc) is a common O-linked glycosylation of protein serine or threonineresidues.

Many cellular proteins, including enzymes &transcription factors, are regulated by reversibleGlcNAc attachment.

Often attachment of GlcNAc to a protein OHalternates with hos hor lation with these 2


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N-linked oligosaccharides of glycoproteins tend tobe complex and branched. First N-acetylglucosamine is linked to a protein via theside-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

sn

X

Ser orThr

N-acetylglucosamine

Initial sugar in N-linke

glycoprotein oligosacchari e


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Additional monosaccharides are added, and the N-linked oligosaccharide chain is modified by removaland addition of residues, to yield a characteristicbranched structure.

NAN

Gal

NAG

Man

NAG

Gal

NAN

Man

Man

NAG

Gal

NAN

NAG

NAG

A n

Fuc

N-linked oligosaccharide

Key:NAN

= etylneuraminateGal = alact se

NAG= acetyl lucosamine

Man= mannoseFuc = fucose


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Many proteins secreted by cells have attached N-

linked oligosaccharide chains.Genetic diseases have been attributed to deficiencyof particular enzymes involved in synthesizing ormodifying oligosaccharide chains of these

glycoproteins.Such diseases, and gene knockout studies in mice,have been used to define pathways of modificationof oligosaccharide chains of glycoproteins and

glycolipids.

Carbohydrate chains of plasma membraneglycoproteins and glycolipids usually face theoutside of the cell.


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Lectins are glycoproteins that recognize and bind to specificoligosaccharides.

ConcanavalinA & wheatgermagglutinin are plant lectinsthat have been useful research tools.

The C-typelectin-likedomain is a Ca++-bindingcarbohydraterecognition domain in many animallectins.

Recognition/bindingofCHO 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.


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Examples of animal lectins:

Mannan-bindinglectin (MBL) is a glycoproteinfound in blood plasma.

It binds cell surface carbohydrates ofdisease-

cau

singmicroorganisms & promotesphagocytosis of these organisms as part of theimmune response.


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A cleavagesitejust outside the transmembrane E-

helix provides a mechanism for regulated release ofsome lectins from the cell surface.

A cytosolicdomain participates in regulated

interaction with the actin cytoskeleton.

tr nsm mbr n

E-h lix

l tin dom ins l tin

ytos l tonbinding dom in

ytosol

outsid

Selectins are integralproteins of mammalian cellplasma membranes withroles in cell-cellrecognition & binding.

The C-type lectin-likedomain is at the end of amulti-domain extracellularsegment extending out from

the cell surface.


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An oligosaccharide (shown in grey)

bound in the binding site of a plant lectin

(Griffonia simplicifolia isolectin IV incomplex with the Lewis b blood group

determinant). Only a part of the

oligosaccharide is shown for clarity


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Carbohydrates

Molecular Biochemistry I

0 carbohydrate chemistry 1

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