L16 L17 Carbohydrates 2013 14
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Transcript of 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