L16 L17 Carbohydrates 2013 14

8/12/2019 L16 L17 Carbohydrates 2013 14

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Module BIO00004C

Molecular Biology and Biochemistry

Lectures 16-17Christoph Baumann([email protected])

Introduction to

Structure and Function of Carbohydrates

Learning Outcomes

At the end of these lectures you should know:

what are carbohydrates

the basic structure of some important

monosaccharides, disaccharides and polysaccharides the functions of carbohydrates in prokaryotic and

eukaryotic cells


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Cellulose

Chitin

Starch

Sucrose


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Extensive roles in all forms of life

As monosaccharidesand disaccharidesthey are..

used as energy stores, fuels and metabolic intermediates important in the structural backbone of DNA and RNA

As polysaccharidesthey are..

structural elementswalls of plants and bacteriaextracellular matrixconnective tissuelubrication of skeletal joints

linked to proteins and lipidscell-cell recognitioncell adhesionintracellular localisation tags on glycoproteinsdetermine metabolic fate of glycoconjugates


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Carbohydrates in BiomedicineErythropoietin glycosylated protein in serum that stimulates red blood cellproduction

A, B and O blood groups 3 different carbohydrates on surface of bloodcells

Heparin glycosaminoglycan commonly used as a blood thinner

Arthritis proteolytic degradation of collagen in cartilage

Congenital lysosomal storage disorders(mucolipidosis II) enzymesresponsible for degrading glycosaminoglycans are missing from lysosomes

Influenza virus enters cells by binding to sialic acid residues present on cell-surface glycoproteins (hemagglutinin)


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Carbohydrates in Biotechnology

Agarose(crosslinked D-galactose and 3,6-anhydrogalactose)

Dextran(crosslinked !-1,6-D-glucose)

Lectins applications as anti-tumor and anti-infective compounds

Glycodendrimers DNA- or drug-delivery systems, materials science


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L-glyceraldehyde

CH

C

HO

CH2OH

O H

OH

O

C

H

CH2OH

H

C

C H

O

C

HO

C OH

H

H

H

C OH

O

C

H

C OH

H

H

H

Glyceraldehyde, the simplest carbohydrate(Fischer projection)

D-glyceraldehyde

enantiomers

mirror image


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How to Visualise the Fischer Projection of anOrganic Molecule?


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D-Aldoses containing three, four, five and six carbons

Triose

Tetrose

Pentose

Hexose

Diastereomers(not mirror images)

Epimers


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D-Ketoses containing three, four, five and six carbons

Tetrose

Pentose

Hexose

Diastereomers


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For example: Hexose C6H12O6 48 possible structures

Monosaccharides of the same chemical composition can varytremendously in their structure

Aldoses: 8 D, 8 L, !

8 D, 8 L, "

Ketoses: 4 D, 4 L,!

4 D, 4 L, "

32

16


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Ring formation

D-Glucose

(open chain)

C OH

O

C

H

H

C HHO

C OHH

C OHH

CH2OH

1

2

3

4

5

6

O

O

H

OHHO

CH2OH H

OHH

HH

H

23

4

5

6

1

O

OHHO

CH2OH

OHH

HH

H

23

4

5

6

1

OH

H

O

OH

HO

CH2OH

OHH

HH

H

23

4

5

6

1

H

OH

-D-Glucose(!-D-Glucopyranose)

-D-Glucose("-D-Glucopyranose)

30 %

70 %

< 1 % hemiacetal


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Reducing Sugars

Fehlings reagent

"-D-glucopyranose

Glucose(open chain)

Oxidisedopen chain

Aldehyde group is easily oxidised by Cu2+ (Fehlings reagent) thus they are known as reducing sugars


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Different ways to depict "-D-Glucose

1

3

5

6

24

Fischer

C OH

O

C

H

H

C HHO

C OHH

C OHH

CH2OH

1

2

3

4

5

6

O

OHHO

CH2OH

OHH

HH

H

23

4

5

6

1

OH

H

Haworth

O

H

CH2OHHO

HO

H

OHH

H

H

OH123

45

6

Conformation :chair / all equatorial

Space-fillingmodel


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Chairand BoatForms of !-D-Glucopyranose

a = axial position e= equatorial position

H

HO

H

HO

OH

CH2OH

HO

H

H

OH

O

H

HO

H

HO

H

H

OHH

CH2OH

OH

chairform boatforma

e

e

a

ee

e

aa

e

a

e

e

e

e

aa

a

aa


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Fructose forms pyranose and furanose rings

-D-Fructopyranose

D-Fructose

(open chain)

C O

CH2OH

C HHO

C OHH

C OHH

CH2OH

1

2

3

4

5

6

O

O

CH2OH

H

HO

H

HOH

HOH

H

34

5

6

2

H1

O CH2OH

H

HO

HOH

HOH

H

34

5

6

H1

OH

2

O

O

CH2OH

HH

H

HOH

HO

34

5

6

2

1

HOCH2 O

H

H

HOH

HO

34

5

6

CH2OH1

OH

2

-D-Fructofuranose

O

H

H

HOH

HO

34

5

6

OH

1

2

-D-FructofuranoseCH2OH

HOCH2

HOCH2

hemiketal


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Ribose

"-D-Ribose

O

HH

OHOH

H

23

4

5

HOCH2 OH

1

H

2-Deoxy-"-D-Ribose

O

H

H

HOH

H

23

4

5

HOCH2 OH

1

H

2-deoxy

H H

H H

H


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Glycosidic linkage

"-D-GalactoseH2O

O

O

OH

HO

CH2OH

OHH

HH

H23

4

5

6

1

H

O

OH

CH2OH

OHH

HH

H

23

4

5

6

1

OH

H

Gal-"-1,4-Glc

Lactose

"-D-Glucose

OHO

OH

HO

CH2OH

OHH

HH

H23

4

5

6

1

H

O

OHHO

CH2OH

OHH

HHH

23

4

5

6

1

OH

H


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Glc-!-1,4-Glc

Maltose

O

O

OHHO

CH2OH

OHH

H

HH

23

4

5

6

1

H O

OH

CH2OH

OHH

H

HH

23

4

5

6

1

OH

H

!- D-Glc-1,2-"-D-Fru

Sucrose

O

OHHO

CH2OH

OHH

HH

H

23

4

5

6

1

H

O

HH

HOH

HO34

5

6

HOCH2

O

1

2

CH2OH


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Some important sugar derivatives

O

OHHO

CH2OH

NH2H

HH

H

23

4

5

6

1

OH

H

D-Glucosamine(GlcN)

O

OHHO

CH2OH

H

HH

H

23

4

5

6

1

OH

H

NHC O

CH3

D-Glucuronic acid(GlcUA)

O

OHHO

C

OHH

HH

H

23

4

5

6

1

OH

H

O O

N-Acetyl-D-Glucosamine

(GlcNAc)

N-Acetylmuramic acid(NAM)

NHC O

CH3

O

OHO

CH2OH

H

HH

H

23

4

5

6

1

OH

H

C COOHH3C

H


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Phosphorylated sugars are key intermediatesin energy generation and biogenesis

O

OHHO

CH2OPO32-

OHH

H

HH

23

4

5

6

1

H

OH

Glucose 6-phosphate(G-6P)

Dihydroxyacetonephosphate

(DHAP)

CH2OHC O

CH2OPO32-

Glyceraldehyde3-phosphate

(GAP)

CH2OPO32-

C OH

CHO

H


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Polysaccharides

Homopolysaccharides

Heteropolysaccharides

BranchedUnbranched

Multiplemonomer types,

branched

Twomonomer types,

unbranched


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Polysaccharides for the storage of glucose


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Glycogen granules in liver cell

Storage of glucose: Glycogen

--Glc-!-1,4-Glc--

!-1,6 branchingevery 8-12 residues

OO

OOOO

OO

O

O O

O

O

O

OO

O

O

O

OO

O

OOOO

O

reducing

end

non-reducingends


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!-1,4 linkage

Starch granules in plant cell

Storage of glucose in plants: Starch

Amylose

Amylopectin

Nonreducingends

1) -Amylose--Glc--1,4-Glc--

2) Amylopectin--Glc--1,4-Glc--

-1,6-branchingevery 24 - 30 residues

Reducingends


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Polysaccharides: Structural roles


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Microfibril

Primarywall

Pectin

CelluloseHemicellulose

Plasma

membrane

Plant cell wallsCellulose: --Glc-"-1,4-Glc--

l l h d


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Storage versusstructural polysaccharides

!-Amylose--Glc-!-1,4-Glc--

Cellulose--Glc-"-1,4-Glc--

Chitin--GlcNAc-"-1,4-GlcNAc-

O

O

OH

CH2OH

OHH

HH

H H

O

O

OH

CH2OH

OHH

HH

H H

O

O

OH

CH2OH

OHH

HH

H H

O

O

OH

CH2OH

OHH

HH

H H

O

O

OH

CH2OH

OHH

HH

H H

O

O

OH

CH2OH

OHH

HH

H H

O

O

OH

CH2OH

OHH

HH

H

H

O

O

OH

CH2OH

OHH

HH

H

H

O

O

OH

CH2OH

OHH

HH

H

H

O

O

OH

CH2OH

OHH

HH

H

H

O

O

OH

CH2OH

OHH

HH

H

H

O

O

OH

CH2OH

OHH

HH

H

H

O O

HO

O

OH

CH2OH

NHH

HH

H

O

C O

CH3C

O

OH

CH2OH

NHH

HH

H

O

C O

CH3C

O

OH

CH2OH

NHH

HH

H

O

C O

CH3C

O

OH

CH2OH

NHH

HH

H

O

C O

CH3C

O

OH

CH2OH

NHH

HH

H

O

C O

CH3C

O

OH

CH2OH

NHH

HH

H

O

C O

CH3C


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Peptidoglycan in bacterial cell envelope

NH2

C O

CH3

O

O

O

CH2OH

H

HH

H

23

4

5

6

1

H

O

OH

CH2OH

H

HH

H

23

4

5

6

1

H

NH2

C O

CH3

CH

H3C

COO

OO

lactyl

N-Acetylmuramic acid

(MurNAc orNAM)

--MurNAc-"-1,4-GlcNAc--

M M MGG G

M M MGG G

M M MGG G

Lysozyme

N-Acetyl-D-glucosamine(GlcNAc)

oligopeptide


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M GG

M MG

L-Ala

D-Glu

DAP

D-Ala

D-Ala

L-Ala

DAP

D-Glu

D-Ala

D-Ala

Penicillins inhibit glycopeptide transpeptidaseactivity

M GG

M MG

L-Ala

D-Glu

DAP

D-Ala

D-Ala

L-Ala

D-Ala

DAP

D-Glu

D-Ala

DAP = diaminopimelic acid

H3N CH C

CH2

O

O

CH2

CH2

HC

NH3

C O

O


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M GG

M MG

L-Ala

D-Glu

DAP

D-Ala

D-Ala

L-Ala

DAP

D-Glu

D-Ala

D-Ala

Penicillins inhibit glycopeptide transpeptidaseactivity

M GG

M MG

L-Ala

D-Glu

DAP

D-Ala

D-Ala

L-Ala

D-Ala

DAP

D-Glu

D-Ala

O

HN

N

S

C

O

O

CH3

CH3

R

O

"-lactam ring

/


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Bacterial cell envelope / PeptidoglycanGram positiveStaphylococcus aureus

Lipid bilayermembrane

Peptidoglycan

(cell wall)Polysaccharidecoat

Lipoteichoic acid

MurNAc

GlcNAc

Tetrapeptide(Gly)5

MurNAc

Gram negativeEscherichia coli

Cross-linkedTetrapeptides

Periplasmicspace

Lipid bilayermembrane

Peptidoglycan

Outer lipidmembrane

MurNAc

GlcNAc

MurNAc

Lipopolysaccharide


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Roles of carbohydrates in

cellular recognition processes


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Glycoproteins: glycosidic bonds betweenproteins and carbohydrates

N-linked GlcNAc O-linked GalNAc


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Glycoproteins

O

NH Asn

O

O OOO

Man

Man

Man

GlcNAc

O

Man

O

ManO

Man

OMan

O

GlcO

GlcO

Glc

OMan

OMan

O

NH Asn

O

O OOO

Man

Man

Man

GlcNAc

O

Man

O

ManO

Man

O

Man OMan

OMan

Example: N-Glycans

Primary

Processing


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N-linked glycosylationbegins inthe endoplasmic reticulum (ER)

and continues in the Golgi

O-linked glycosylationoccursin the Golgi

Different glycosylationenzymes are present in eachcompartment (cisternae) of

the Golgi

plasma membrane

Golgi

ER

ER

cis

trans

Glycosylation in the Cell


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O

NH Asn

O

OOOMan

Man

GlcNAc

O

Man

O

NH AsnOOO

ManO

Man

O

Man

O

O

OO

OO

Gal

GalOO

OO

Sia

OO

Sia

OL-Fuc

GlcNAc

Processing

Modification


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Carbohydrates as components

of the extracellular matrix


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Actin filaments

Integrin

Proteoglycan

Fibronectin

Collagen

Plasma membrane

Extracellular Matrix (ECM)

Cell adhesion protein

Multiadhesiveprotein

Collagenfiber

PM

PM


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Glycosaminoglycans:Components of the extracellular matrix

"-1,3

GlcNAc

O

O

COO

GlcUA

O

O

COO

O

O

COO

"-1,4Hyaluronic acid

Chondroitin-6-sulfate"-1,3

GalNAc

-6-sulfate

O

O

COO

GlcUA

O

O

COO

O

O

COO

"-1,4

OSO3

OSO3

OSO3

Keratan sulfate"-1,3

GalNAc

-6-sulfate

O

GalO "-1,4

OSO3

O

GalO

OSO3

OGal

O

OSO3


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Proteoglycan structure in cartilage

Hyaluronate Chondroitin sulfate

Proteoglycan

Core protein

Keratan sulfate Link protein

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L16 L17 Carbohydrates 2013 14

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