Download CARBOHYDRATES 2016

CARBOHYDRATES
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CARBOHYDRATES
Empirical formula: C x (H2O)y
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CARBOHYDRATES- WHERE ARE THEY ?
In solid parts of:
plants, up to 80%
animals, does not exceed 2%
In plants:
– mainly as a storage material (starch)
– building material (celulose)
In animals:
– source of energy
– building material:
• Skeleton of invertebrates and mushrooms (chitinous –
protective polysacharide substance)
• Structural function in vertebrates (glycosoaminoglycans)
[ Invertebrates – animal without skeleton ]
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CARBOHYDRATES CLASSIFICATION
Monosacharides – simple sugars with multiple OH groups.
Carbohydrates which can not be divided to other carbohydrates
components
Disacharides – 2 monosaccharides covalently linked. During hydrolysis
they are degrade to two compounds of monosaccharide, for example:
maltose, saccharose
Oligosacharides – a few monosaccharide covalently linked.
during hydrolysis they are degrade to 3 to 10 units of monosaccharide
e.g. :maltotrioza
Polysacharides – polymers consisting of chains of monosaccharide or
disaccharide units. During hydrolysis they are degrade to over 10
molecules of monosacharides, e.g.: starch, glycogen.
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Carbohydrates - occurrence
Proteins + short chains carbohydrates– glycoproteins
Proteins + long chains of carbohydrates – proteoglycans
glycocalyx – intracellular structure :
glycoproteins + proteoglycans + glycolipids
-
protects the surface of the cells against mechanical and chemical
damages
it facilitates the movement of motile cells
prevents the agglomeration of cells, and from sticking to the walls of the
vessel
acts as a mutual recognition between cells
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PHYSICAL PROPERTIES OF
MONOSACHARIDES
COLORLESS, ODOURLESS
USUALLY TASTE SWEET
VERY WELL SOLUBLE IN WATER
ROTARY POLARIZATION
NEUTRAL CHEMICALLY (NO ACIDITY OR
BASISITY)
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MONOSACHARIDES - NOMENCLATURE
Monosacharides containing:
Aldehyde group are called - aldose
Ketone group are called - ketose
Aldoses (e.g., glucose) have
an aldehyde group at one end.
H
Ketoses (e.g., fructose) have a
ketone group, usually at C2.
O
C
H
C
C H 2O H
OH
HO
C
H
H
C
OH
H
C
OH
CH 2 O H
D -glucose
C
O
HO
C
H
H
C
OH
H
C
OH
C H 2O H
D -fructose
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TYPE OF MONOSACHARIDES
ISOMERISM
1.
2.
3.
4.
5.
6.
Configuration of D and L isomers
Optical isomerism
Piranoses and furanoses ring forms
Anomers α and β
Epimers
Isomers
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CONFIGURATION D and L
Molecules of glyceric aldehyde
are enantiomers.
Stereoisomers are isomeric molecules that have the same
molecular formula and sequence of bonded atoms (constitution),
but which differ only in the three-dimensional orientations of their
atoms in space.
Also are called mirror images (enantiomers).
• If certain compound can be transformed to one of glyceric
aldehyde isomers then this compound belongs to D or L .
• D or L does not depend on rotary polarization.
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ISOMERS D and L
L-glyceric aldehyde
D-glyceric aldehyde
O
O
1C
1C
–H

–H

H – 2C – OH

HO – 2C – H

3CH OH
2
D and L symbols determine
sugars configuration, starting
with one before last carbon atom
from aldehyde group.
Reference is glyceric aldehyde.
3CH OH
2
1CHO
L-glucose

2
HO – C – H

H – 3C – OH

HO – 4C – H

5
HO – C – H

6CH OH
2
1CHO

2C
– OH

HO – 3C – H

H – 4C – OH

5
H – C – OH

6CH OH
2
H–
D-glucose
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TYPE L ISOMERS
L-iduronic acid
Fucose
L-fucose-1,6-N-acethyloglucosamine
α-D-fukoza
β-L-fukoza
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OPTICAL ISOMERISM OF
MONOSACHARIDES
Amount of enantiomers pairs
depends on active centers
quantities.
CHO

*CHOH

*CHOH

*CHOH

*CHOH

CH2OH
For 4 centers the
amount of
enantiomers and
diastereoisomers
are 24=16
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FAMILY OF D-aldose
D-(+)- aldehyd glicerynowy
D-(-)-ryboza
D-(-)-arabinoza
D-(-)-ksyloza
D-(-)-liksoza
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Hemiacetal & hemiketal formation
H
An aldehyde
can react with
an alcohol to
form a
hemiacetal.
C
H
O
+
R'
OH
R'
O
R
aldehyde
C
OH
R
alcohol
hemiacetal
R
A ketone can
react with an
alcohol to form
a hemiketal.
C
R
O
+
"R
OH
R'
ketone
"R
O
C
OH
R'
alcohol
hemiketal
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Pentoses and
hexoses can cycles,
as the ketone or
aldehyde reacts
with a distal OH.
Glucose forms an
intra-molecular
hemiacetal, as the
C1 aldehyde & C5
OH group reacts, to
form a 6-membered
pyranose ring,
named after pyran.
C1 is a new center.
1
H
2
HO
3
H
4
H
5
6
CHO
C
OH
C
H
D -glucose
C
OH
(linear form)
C
OH
CH 2OH
6 CH 2 OH
6 CH 2OH
5
H
4
OH
H
OH
3
H
O
H
H
1
2
OH
OH
Alfa
DαD -glucose
α-D-glucopiranoses
glukopiranoses
5
H
4
OH
H
OH
3
H
O
OH
H
1
H
2
OH
β-D -glucose
β-D glucopiranoses
Diastereoisomers = anomers = they differ from each other with
configuration at C1 atom only, and have different physical properties
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CH2OH
1
HO
H
H
2C
O
C
H
C
OH
C
OH
3
4
5
6
HOH2C 6
CH2OH
D-fructose (linear)
H
5
H
1 CH2OH
O
4
OH
HO
2
3
OH
H
α-D-fructofuranose
Fructose forms either:
6-membered pyranose ring, by reaction of the C2 keto group with
the OH on C6, or
a 5-membered furanose ring, by reaction of the C2 keto group with
the OH on C5.
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6 CH2OH
6 CH2OH
5
H
4
OH
H
OH
3
H
O
H
H
1
2
OH
α-D-glucose
α D-glukopiranoses
OH
5
H
4
OH
H
OH
3
H
O
OH
H
1
2
H
OH
D-glucose
β-Dβglucopiranoses
Cyclization of glucose produces a new asymmetric center
at C1. This two 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).
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H OH
H OH
4 6
H O
HO
HO
H O
HO
H
HO
5
3
H
H
2
H
OH 1
OH
α-D-glucopyranose
H
OH
OH
H
β-D-glucopyranose
Because of the tetrahedral nature of carbon bonds,
pyranose sugars actually have a "chair" or "boat"
configuration, depending on the sugar.
The above representation reflects the chair
configuration of the glucopyranose ring more
accurately than the Haworth projection.
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Mutarotation
Mutarotation it is transformation of one anomeric form into another
Intermediate form is chain form of monosaccharide.
In D-glucose solution there is more β-D-glucopyranosis.
All its –OH groups have the most energetically beneficial equatorial position.
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Monosaccharide epimers
Epimers:
Cn aldoza
endiol
Cn ketoza
epimeryczna
Cn aldoza
diasteroisomers differ from each
other with one –OH position
– Different than at C-1 in aldose
– Different than at C-2 in ketose
– Different than at last asymmetric carbon
atom
Pair of epimers:
Glucose and mannos
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Glucose epimers
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Chemical properties of monosacharides
Reductive properties –only when free
aldehyde or ketone group in saccharides
molecule is present.
In alkali environment Saccharides have
reductive properties and ring can be opened
In acidic environment saccharides are in cyclic
form and there is no =CO group.
Saccharides oxidizes to acids , while reduces
other substances e.g.: glucose oxidizes to
gluconic acid
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Chemical properties of monosacharides
Acid inflence on saccharides – all saccharides
with amount of atoms molecule more than 4
during heating with strong acids are dehydrate
and cyclization
BASE INFLUENCE ON SACCHARIDES– in
base environment reductive saccharides get
enolization
Osazone creating - saccharides with phenyl
hydrazine are creating yellow, not soluble in
water dihydrasones called osazone.
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Osazone formation
Epimers have joint osazone
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Sugar derivatives
CHO
COOH
CH2OH
H
H
H
C
C
C
H
C
OH
HO
C
H
OH
H
C
OH
OH
H
C
OH
H
C
OH
HO
C
H
H
C
H
C
OH
OH
OH
CH2OH
D-ribitol
CH2OH
D-gluconic acid
COOH
D-glucuronic acid
sugar alcohol – no aldehyde or ketone group; e.g., ribitol.
sugar acid - the aldehyde group at C1, or OH at C6, is
oxidized to a carboxylic acid; e.g., gluconic acid, glucuronic
acid.
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Sugar derivatives
CH2OH
CH2OH
O
H
H
OH
H
H
OH
H
OH
OH
H
NH2
α-D-glucosamine
O
H
H
H
O OH
OH
H
N
C
CH3
H
α-D-N-acetylglucosamine
amino sugar - an amino group substitutes for an
hydroxyl group. An example is glucosamine.
The amino group may be acetylated, as in
N-acetylglucosamine.
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H
O
H3C
C
O
NH
R
H
COO−
H
R=
OH
H
HC
OH
HC
OH
CH2OH
OH
H
N-acetylneuraminate (sialic acid)
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 proton at
physiological pH, as shown here.
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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' + H2O
E.g., methanol reacts with the anomeric OH in glucose to form
methyl glucoside (methyl-glucopyranose).
H OH
H OH
H2O
H O
HO
HO
H
H
H
+
CH3-OH
H O
HO
HO
H
OH
OH
H
OH
α-D-glucopyranose
H
methanol
OCH3
methyl-α-D-glucopyranose
©
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Glycosidic Bonds
Glycosidic anomers
©
©
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DISACCHARIDES
Disaccharides are consisting of two monosacharides,
and connected by glycoside bond are called O-glycosides.
The most important are:
• saccharose (present in honey, fruits),
• lactose
(present in milk),
• maltose
(product of enzymatic hydrolysis of starch),
• cellobiose (product of cellulose hydrolysis).
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Disaccharides:
Maltose, a cleavage (split)
product of starch (e.g.,
amylose), is a disaccharide
with an α(1→
→ 4)
glycosidic link between C1
- C4 OH of two glucoses.
It is the α anomer (C1 O
points down).
6 CH2OH
6 CH2OH
H
5
O
H
OH
4
OH
3
H
H
H
1
H
4
4
OH
5
H
OH
H
OH
maltose
H
H
1
OH
OH
2OH
6 CH
H
H
1
O
4
5
O
H
OH
H
H
3
H
2
3
O
H
OH
O
O
2
6 CH2OH
H
5
2
OH
3
cellobiose
H
OH
1
H
2
OH
Cellobiose, a product of cellulose breakdown, β 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.
©
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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-Dfructopyranose.)
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
©
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CH2OH
H
O
H
OH
H
H
H
1
O
OH
6CH OH
2
5
O
H
4 OH
3
H
OH
H
H
H
H 1
O
H
OH
CH2OH
CH2OH
CH2OH
H
H
H
O
H
OH
H
O
O
H
H
O
H
OH
H
H
O
OH
2
OH
H
OH
H
OH
H
OH
amylose
Polysaccharides:
Plants store glucose as amylose or amylopectin,
glucose polymers, collectively called starch.
Glucose storage in polymeric form minimizes
osmotic effects.
Amylose is a glucose polymer with α(1→
→4) linkages.
The end of the polysaccharide with an anomeric C1
not involved in a glycosidic bond is called the
©
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reducing end.
CH2OH
CH2OH
O
H
H
OH
H
H
OH
H
O
OH
CH2OH
H
H
OH
H
H
OH
H
H
OH
CH2OH
O
H
OH
O
H
OH
H
H
O
O
H
OH
H
H
OH
H
H
O
4
amylopectin
H
1
O
6 CH2
5
H
OH
3
H
CH2OH
O
H
2
OH
H
H
1
O
CH2OH
O
H
4 OH
H
H
H
H
O
OH
O
H
OH
H
H
OH
H
OH
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.
©
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CH2OH
CH2OH
O
H
H
OH
H
H
OH
H
O
OH
CH2OH
H
H
H
H
O
OH
H
H
OH
H
H
OH
CH2OH
O
H
OH
O
H
OH
O
H
OH
H
H
H
H
O
OH
4
glycogen
H
1
O
6 CH2
5
H
OH
3
H
CH2OH
O
H
2
OH
O
H
H
1
O
CH2OH
H
4 OH
H
H
H
O
OH
O
H
H
OH
H
H
OH
H
OH
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.
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CH2OH
H
O
H
OH
H
OH
H
1
O
H
H
OH
6CH OH
2
5
O
H
4 OH
3
H
H
H 1
2
OH
O
O
H
OH
CH2OH
CH2OH
CH2OH
H
H
O
O
H
OH
H
OH
O
H
O
H
OH
H
OH
OH
H
H
H
H
H
H
H
OH
cellulose
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
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.36
D - g lu c u r o n a t e
6 COO
H
4
6
−
5
H
OH
3
H
CH
H
5
1
H
2
OH
H
O
3
H
O
1
H
OH
O
H
H
4
O
2O
2
H
NH COCH
3
N - a c e t y l- D - g l u c o s a m i n e
h y a lu ro n a te
Glycosaminoglycans (mucopolysaccharides) are linear polymers of
repeating disaccharides. Can be covalently bond to a protein to form
protoglycans.
The constituent monosaccharides tend to be modified with: acidic groups,
amino groups, sulfated hydroxyl groups,etc.
Glycosaminoglycans tend to be negatively charged because of the acidic
groups presence.
It is important component of connective tissues.
Some examples of glycosaminoglycan uses in nature include heparin as
an anticoagulant , hyaluronan as a component in the synovial fluid
lubricant in body joints, and chondroitins, which can be found in
connective tissues, cartilage, and tendons.
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CH2OH
D-glucuronate
6
−
6COO
H
4
5
H
OH
3
H
H
2
OH
1
H
H
OH
O
O
H
4
O
H
5
3
H
2
1 O
H
NHCOCH3
N-acetyl-D-glucosamine
hyaluronate
Hyaluronate (hyaluronan) is a glycosaminoglycan
with a repeating disaccharide consisting of two
glucose derivatives, glucuronate (glucuronic acid) &
N-acetyl-glucosamine.
The glycosidic linkages are β(1→3) & β(1→4).
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core
protein
heparan sulfate
glycosaminoglycan
transmembrane
α-helix
cytosol
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.
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N-sulfo-glucosamine-6-sulfate
iduronate-2-sulfate
CH2OSO3−
H
H
COO−
OH
O
O
H
O
H
H
OH
H
H
H
H
OSO3−
O
H
NHSO3−
heparin or heparan sulfate - examples of residues
Heparan sulfate is initially synthesized on a membraneembedded core protein as a polymer of alternating
N-acetylglucosamine and glucuronate residues.
Later, in segments of the polymer, glucuronate residues may
be converted to the sulfated sugar iduronic acid, while Nacetylglucosamine residues may be deacetylated and/or
sulfated.
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PDB 1RID
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 (coagulated) formation by interacting
with the protein antithrombin.
Heparin has an extended helical
conformation.
heparin: (IDS-SGN)5
Charge repulsion by the many negatively charged groups
may contribute to this conformation.
Heparin shown has 10 residues, alternating IDS (iduronate-2sulfate) & SGN (N-sulfo-glucosamine-6-sulfate).
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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 to
alter affinity
for signal
proteins, e.g.,
N-sulfo-glucosamine-6-sulfate
iduronate-2-sulfate
growth factors.
CH OSO −
H
2
H
COO−
OH
O
O
H
O
H
3
H
OH
H
H
H
H
©
OSO3−
O
H
NHSO3−
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heparin or heparan sulfate - examples of residues
Glycosidic bond
C
CH2OH
Oligosaccharides
that are covalently
attached to proteins or
to membrane lipids
may be linear or
branched chains.
O
H
H
OH
O
CH2
CH
NH
H
O
serine
residue
O H
OH
H
HN
C
CH3
β-D-N-acetylglucosamine
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.
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CH2OH
O
O
H
H
OH
HN
C
HN
CH2
C
H
H
OH
H
HN
C
CH3
O
N-acetylglucosamine
Initial sugar in N-linked
glycoprotein oligosaccharide
Asn
CH
O
HN
HC
R
C
O
X
HN
HC
R
C
O
Ser or Thr
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
3amino acid sequence.
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NAN
NAN
NAN
Gal
Gal
Gal
NAG
NAG
NAG
Man
Man
Man
Key:
NAG
NAG
Asn
N-linked oligosaccharide
Fuc
NAN = N-acetylneuraminate
Gal = galactose
NAG = N-acetylglucosamine
Man = mannose
Fuc = fucose
Additional monosaccharides are added, and the Nlinked oligosaccharide chain is modified by
removal and addition of residues, to yield a
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characteristic branched structure.
Homoglycans
1,4-O-glycoside-bond
1,6-O-glycoside
bond
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Homoglycans - starch
Main storage material for plants. Is consisting of amylopectin and amylose:
Amylopectin, insoluble in water α-1,4- i α-1,6-glycoside bonds
Amylose – soluble in water
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GLYCOGEN
• Homoglycan (in animals) – high
molecular storage material, built form
α-amylose, amylopectine.
• Stored in liver.
• Plays similar role as starch in plants.
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The End
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