Carbohydrates

CARBOHYDRATES

Carbohydrate - polyhydroxy aldehyde, ketones and

their derivatives.
Functions - structure material storage material for
carbon and energy.
 General characteristics
• the term carbohydrate is derived from the french:
hydrate de carbone
• compounds composed of C, H, and O
• (CH2O)n when n = 5 then C5H10O5
• not all carbohydrates have this empirical formula:
deoxysugars, aminosugars
• carbohydrates are the most abundant compounds
found in nature (cellulose: 100 billion tons
annually)
 General characteristics
• Most carbohydrates are found naturally in bound
form rather than as simple sugars
• Polysaccharides (starch, cellulose, inulin, gums)
• Glycoproteins and proteoglycans (hormones, blood group
substances, antibodies)
• Glycolipids (cerebrosides, gangliosides)
• Glycosides
• Mucopolysaccharides (hyaluronic acid)
• Nucleic acids
 Functions
• sources of energy
• intermediates in the biosynthesis of other basic
biochemical entities (fats and proteins)
• associated with other entities such as glycosides,
vitamins and antibiotics)
• form structural tissues in plants and in
microorganisms (cellulose, lignin, murein)
• participate in biological transport, cell-cell
recognition, activation of growth factors,
modulation of the immune system
 Classification of carbohydrates
• Monosaccharides (monoses or glycoses)
• Trioses, tetroses, pentoses, hexoses
• Oligosaccharides
• Di, tri, tetra, penta, up to 9 or 10
• Most important are the disaccharides
• Polysaccharides or glycans
• Homopolysaccharides
• Heteropolysaccharides
• Complex carbohydrates
Carbohydrates (glycans) have the following
basic composition: I
(CH2O)n or H - C - OH
I
 Monosaccharides - simple sugars with multiple OH
groups. Based on number of carbons (3, 4, 5, 6), a
monosaccharide is a triose, tetrose, pentose or hexose.
 Disaccharides - 2 monosaccharides covalently linked.
 Oligosaccharides - a few monosaccharides covalently
linked.
 Polysaccharides - polymers consisting of chains of
monosaccharide or disaccharide units.
 Monosaccharides
• also known as simple sugars
• classified by
– the number of carbons and
– whether aldoses or ketoses
• most (99%) are straight chain compounds
• D-glyceraldehyde is the simplest of the aldoses
(aldotriose)
• all other sugars have the ending ose (glucose,
galactose, ribose, lactose, etc…)
 Aldose sugars
H H H H H

C O C O C O C O C O

(H C OH)n H C OH H C OH H C OH H C OH

CH2OH CH2OH H C OH H C OH H C OH

Aldose Aldotriose CH2OH H C OH H C OH

n=1
Aldotetrose CH2OH
n=2 H C OH
Aldopentose
CH2OH
n=3
Aldohexose
n=4
 Ketose sugars

CH2OH CH2OH
CH2OH
CH2OH
C O C O CH2OH
C O
C O
(H C OH)n H C OH C O
H C OH
CH2OH
CH2OH H C OH H C OH
CH2OH
CH2OH H OH
Ketose Ketotriose Ketotetrose
n=1 Ketopentose H C OH
n=0
n=2
CH2OH
Ketohexose
n=3
Structure of a simple aldose and a simple ketose
 Enantiomers and epimers
H H
H H C O C O
C O C O HO C H HO C H
H C OH OH C H HO C H HO C H
H C OH OH C H H C OH HO C H
CH2OH CH2OH
H C OH H C OH
these two aldotetroses are enantiomers.
They are stereoisomers that are mirror CH2OH CH2OH
images of each other
these two aldohexoses are C-4 epimers.
they differ only in the position of the
hydroxyl group on one asymmetric carbo
(carbon 4)
 Properties
• Differences in structures of sugars are
responsible for variations in properties
– Physical
• Crystalline form; solubility; rotatory power
– Chemical
• Reactions (oxidations, reductions, condensations)
– Physiological
• Nutritive value (human, bacterial); sweetness;
absorption
 Structural representation of sugars

• Fisher projection: straight chain

representation
• Haworth projection: simple ring in
perspective
• Conformational representation: chair and
boat configurations
 Monosaccharides
Aldoses (e.g., glucose) have Ketoses (e.g., fructose) have
an aldehyde group at one end. a keto group, usually at C2.
H O
C CH2OH

H C OH C O

HO C H HO C H

H C OH H C OH

H C OH H C OH

CH2OH CH2OH

D-glucose D-fructose
 CONCEPTS OF ISOMERS

Two or more different compounds which contain the

same number and types of atoms and the same
molecular weights.

Projection formula (spatial arrangement to represent 3-

dimensional structure):
 D vs L Designation

CHO CHO
D & L designations
H C OH HO C H
are based on the
configuration about CH2OH CH2OH
the single asymmetric D-glyceraldehyde L-glyceraldehyde
C in glyceraldehyde.
CHO CHO
The lower H C OH HO C H
representations are
CH2OH CH2OH
Fischer Projections.
D-glyceraldehyde L-glyceraldehyde
 CHO
H C OH
CH2 OH

D-glyceraldehyde (hydroxy group at the highest numbered

asymmetric carbon atom is written to the right):

CHO
HO C H
CH2 OH

L-glyceraldehyde (hydroxy group at the highest numbered

asymmetric carbon atom is written to the left):
D-Erythrose is the mirror image of L-Erythrose.
Glyceraldehydes: Model compounds of monosaccharides

D-Glyceraldehyde L-Glyceraldehyde
H O H O
C C
H C OH HO C H
CH2 OH CH2 OH

D-Erythrose L-Threose
H O H O
C C
H C OH H C OH
H C OH HO C H
CH 2 OH CH2 OH
 FISHER PROJECTION FORM
H O H OH HO H
C C C
H C OH H C OH H C OH
HO C H HO C H O HO C H O
or
H C OH H C OH H C OH
H C OH H C H C

CH2 OH CH2 OH CH2 OH

Anomeric Carbon --- The carbon atom which is

involved in hemiacetal or acetal formation.
Anomers: Stereoisomers formed when ring is formed (a, b).

H O H OH HO H
C C C
H C OH H C OH H C OH
HO C H O HO C H or O HO C H
H C OH H C OH H C OH
HO C H C H C H
CH2 OH CH2 OH CH2 OH

a is same side with ring

 Rules for drawing Haworth
projections
• draw either a six or 5-membered ring
including oxygen as one atom
O O

• most aldohexoses are six-membered

• aldotetroses, aldopentoses, ketohexoses are
5-membered
 Rules for drawing Haworth
projections
• next number the ring clockwise starting next to the
oxygen
5
O O
4 1 4 1

3 2 3 2

• if the substituent is to the right in the Fisher

projection, it will be drawn down in the Haworth
projection (Down-Right Rule)
 Rules for drawing Haworth
projections
• for D-sugars the highest numbered carbon
(furthest from the carbonyl) is drawn up.
For L-sugars, it is drawn down
• for D-sugars, the OH group at the anomeric
position is drawn down for a and up for b.
For L-sugars a is up and b is down
HAWORTH PROJECTION FORMULAS FOR SUGARS

H OH
6
C CH2 OH
H C OH O
5
HO C H O 4 1
OH
H C OH HO
3 2 OH
H C OH

CH2 OH

a - D - Glucopyranose
HAWORTH PROJECTION FORMULAS FOR SUGARS

H OH H OH
C C
H C OH H C OH
O
HO C H HO C H O
H C H C OH
H C OH H C
CH 2 OH CH 2 OH

a -D-Glucofuranose H
a -D-Glucopyranose (35%)
O
C
(0.5%)
H C OH
HO C H
H C OH Aldehydo-D-glucose (0.03%)
H C OH
CH 2 OH

HO H H
HO
C
C
H C OH
O H C OH
HO C H HO C H O
H C H C OH
H C OH H C
CH 2 OH
CH 2 OH

b -D-Glucofuranose (0.5%) b -D-Glucopyranose (0.5%)

 Sugar Nomenclature

For sugars with more O H O H

than one chiral center, C C
D or L refers to the H – C – OH HO – C – H
asymmetric C farthest HO – C – H H – C – OH
from the aldehyde or H – C – OH HO – C – H
keto group. H – C – OH HO – C – H
CH2OH CH2OH
Most naturally occurring
D-glucose L-glucose
sugars are D isomers.
D & L sugars are mirror O H O H
images of one another. C C
They have the same H – C – OH HO – C – H
name, e.g., D-glucose HO – C – H H – C – OH
& L-glucose. H – C – OH HO – C – H
Other stereoisomers H – C – OH HO – C – H
have unique names, CH2OH CH2OH
e.g., glucose, mannose, D-glucose L-glucose
galactose, etc.
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).
 Hemiacetal & hemiketal formation

H H
An aldehyde can
react with an
C O + R' OH R' O C OH

alcohol to form R R
a hemiacetal. aldehyde alcohol hemiacetal

R R
A ketone can
react with an C O + "R OH "R O C OH
alcohol to form R' R'
a hemiketal. ketone alcohol hemiketal
 1
CHO
Pentoses and
H C OH
hexoses can cyclize 2
HO C H
as the ketone or 3 D-glucose
aldehyde reacts H C OH (linear form)
4
with a distal OH. H
5
C OH

Glucose forms an 6
CH2OH
intra-molecular 6 CH2OH 6 CH2OH
hemiacetal, as the 5 O 5 O
H H H OH
C1 aldehyde & H H
4 H 1 4 H 1
C5 OH react, to OH OH
OH OH OH H
form a 6-member 3 2 3 2

pyranose ring, H OH H OH

named after pyran. a-D-glucose b-D-glucose

These representations of the cyclic sugars are called

Haworth projections.
 1
CH2OH

2C O

HO C H
1 CH2OH
3 HOH2C 6 O
H C OH HO
4 5 H 2

H C OH H 4 3 OH
5
OH H
6
CH2OH

D-fructose (linear) a-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.
Fructose (levulsoe) --- Rotation in polarimeter is left

CH2 OH CH2 OH CH2 OH

OH
C O HO C C
HO C H HO C H HO C H
O or O
H C OH H C OH H C OH
H C OH H C H C

CH2 OH CH2 OH CH2 OH

D-Fructose b-D-Fructose a-D-Fructose

Fructose (levulsoe)

HOCH2 O CH2 OH
HOCH2 O OH

HO HO
CH2 OH
OH
OH OH

b - D - Fructofuranose a - D - Fructofuranose

CH2 OH CH2 OH
OH H
C O C
O CH2 OH
HO C H HO C H
OH
H C OH H C OH O
OH OH
H C OH H C OH
H C OH
CH2 OH
H

Naturally-occurring free form

 6 CH2OH 6 CH2OH
5 O 5 O
H H H OH
H H
4 H 1 4 H 1
OH OH
OH OH OH H
3 2 3 2
H OH H OH
a-D-glucose b-D-glucose

Cyclization of glucose produces a new asymmetric center

at C1. The 2 stereoisomers are called anomers, a & b.
Haworth projections represent the cyclic sugars as having
essentially planar rings, with the OH at the anomeric C1:
 a (OH below the ring)
 b (OH above the ring).
 H OH H OH
4 6 H O H O
HO 5 HO
HO 2 H HO OH
3 H OH 1 H OH
H OH H H

a-D-glucopyranose b-D-glucopyranose

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.
 Sugar derivatives
COOH CHO
CH2OH
H C OH H C OH
H C OH
HO C H HO C H
H C OH
H C OH H C OH
H C OH
H C OH H C OH
CH2OH
CH2OH COOH
D-ribitol
D-gluconic acid D-glucuronic acid

 sugar alcohol - lacks an aldehyde or ketone; 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.
 Sugar derivatives
CH2OH CH2OH

H O H H O H
H H
OH H OH H
OH OH OH O OH
H NH2 H N C CH3
H
a-D-glucosamine a-D-N-acetylglucosamine

amino sugar - an amino group substitutes for a hydroxyl.

An example is glucosamine.
The amino group may be acetylated, as in
N-acetylglucosamine.
 O H

H3C C NH O COO−
R HC OH
H H R=
HC OH
H 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 a proton
at physiological pH, as shown here.
 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 on glucose
to form methyl glucoside (methyl-glucopyranose).

H OH H OH
H O H2O H O
HO HO
HO H + CH3-OH HO H
H OH H OH
H OH H OCH3
a-D-glucopyranose methanol methyl-a-D-glucopyranose
 6 CH2OH 6 CH2OH

Disaccharides: H
5 O H H
5 O H
H H
Maltose, a cleavage 4 OH H 1 4
OH H 1

product of starch OH 3 2
O
3 2
OH

(e.g., amylose), is a H OH maltose H OH

disaccharide with an
a(1→ 4) glycosidic 6 CH2OH

5
6 CH2OH

O 5 O OH
link between C1 - C4 H
H
H
H
OH of 2 glucoses. 4
OH H 1 O 4
OH H 1

H
It is the a anomer OH H
3 2 3 2

H OH H OH
(C1 O points down). cellobiose
Cellobiose, a product of cellulose breakdown, is the
otherwise equivalent b anomer (O on C1 points up).
The b(1→ 4) glycosidic linkage is represented as a zig-zag,
but one glucose is actually flipped over relative to the other.
Disaccharides (anydrides of 2 monosaccharides):

Maltose: 4-0-a-D-Glucopyranosyl (1−>4) a-D-

Glucopyranose

CH2 OH CH2 OH
O O

OH OH
HO O
OH
OH OH
 Cellobiose
4-0-b-D-Glucopyranosyl (1−>4)-b-D-Glucopyranose

CH2 OH CH2 OH
O O OH

O OH
OH
HO

OH OH
 Sucrose
2-0-a-D-Glucopyranosyl b-D-Fructofuranoside

CH2 OH
1
O CH2 OH O H

OH 2 5
HO HO
O 3 4 CH2 OH
OH 6
OH

Invert Sugar --- when sucrose in solution, the rotation changes

from detrorotatory (+66.5) to levorotatory (-19.8). So, sucrose is
called “Invert Sugar”. Sucrose has been hydrolyzed into glucose
and fructose.
 Lactose
Principal sugar in milk

CH2 OH CH2 OH
OH O O
O
OH OH
OH
OH OH

4-0-b-D-Galactopyranosyl (1−>4)-a-D- Glucopyranose

4-0-b-D-Galactopyranosyl (1->4)-b-D-Glucopyranose
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 a (O points down from ring), the linkage is a(1→2).
The full name of sucrose is a-D-glucopyranosyl-(1→2)-
b-D-fructopyranose.)
 Lactose, milk sugar, is composed of galactose &
glucose, with b(1→4) linkage from the anomeric OH of
galactose. Its full name is b-D-galactopyranosyl-(1→ 4)-
a-D-glucopyranose
 Oligosaccharide
Raffinose (Galactose + Glucose + Fructose)
6-0-a-D-Galactopyranosyl (1->6)-2-0-a-D-Glucopyranosyl (1-
>2)-b-D-Fructofuranoside

CH2 OH
OH O CH2

O O CH2 OH O
OH
OH HO
OH O
OH CH2 OH
OH OH

Melbiose Sucrose Moiety

 Stachyose (Galactose + Galactose + Glucose + Fructose)
6-0-a-D-Galactopyranosyl (1−>6)-6-0-a-D-Galactopyranosyl (1-> 6)
-2-0-a-D-Glucopyranosyl-b-D-Fructofuranoside
“Flatulence Factor”

CH 2 OH
OH O CH2

O O CH2
OH OH
O O CH2OH O
OH
OH
OH HO
OH OH O
CH2OH
OH OH
 CH2OH 6CH OH CH2OH CH2OH CH2OH
2
O 5 O H O H O H H O H
H H H H H
H H H H H
OH H 1 4 OH H 1 OH H OH H OH H
O O O O OH
OH 2
3
H OH H 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 a(1→4) linkages.
The end of the polysaccharide with an anomeric C1 not
involved in a glycosidic bond is called the reducing end.
 POLYSACCHARIDE
Anhydrides of Monosaccharides Through ether b linkages.
Cellulose --- polymer of b-D-Glucose (1, 4) linkage.
Repeating cellobiose moiety.

CH2 OH CH2 OH CH2 OH CH2 OH

O O O O

OH
O
OH
O
OH
O OH
OH
OH OH OH OH
n
 STARCH

The reserve carbohydrate of plants. Occurs as granules

in the cell. Made of amylose and amylopectin.
Amylose --- ploymer of a-D- Glucose (1−>4) linkage-
straight-chain.

CH2 OH CH2 OH CH2 OH CH2 OH

O O O O

OH OH OH OH
OH
O O O
OH OH OH OH
 Amylopectin

Polymer of a-D-Glucose (1->4) linkage in addition to

a-D-Glucose (1−>6) linkage.

The length of linear units in amylopectin is only 25.

a-(1−>4) linkage (25) to a-(1−>6) linkage.
 PECTIN

Polymer of 4-0-a-D-Galacturonic acid (1 -> 4) &

Methylgalacturonate

COOH COOCH3 COOCH3 COOH

OH O O O O

OH O O O
OH OH OH

OH OH OH OH
 CH 2OH CH 2OH
H O H H O H amylopectin
H H
OH H OH H 1
O
OH
O
H OH H OH

CH 2OH CH 2OH 6 CH 2 CH 2OH CH 2OH

H O H H O H H 5 O H H O H H O H
H H H H H
OH H OH H OH H 1 4 OH H OH H
4 O O
O O OH
OH 2
3
H OH H OH H OH H OH H OH

Amylopectin is a glucose polymer with mainly a(1→4)

linkages, but it also has branches formed by a(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.
 CH2OH CH2OH
H O O
glycogen
H H H
H H
OH H OH H 1
O
OH
O
H OH H OH

CH2OH CH2OH 6 CH2 CH2OH CH2OH

H O H H O H H 5 O H H O H H O H
H H H H H
OH H OH H OH H 1 4 OH H OH H
4 O O
O O OH
OH 2
3
H OH H OH H OH H OH H OH

Glycogen, the glucose storage polymer in animals, is

similar in structure to amylopectin.
But glycogen has more a(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.
 CH2OH 6CH OH CH2OH CH2OH CH2OH
2
O 5 O O H O H O OH
H H H
H H H H H
OH H 1 O 4 OH H 1 O OH H O OH H O OH H
OH H H H
H 2 H
3
H OH H OH H OH H OH H OH
cellulose
Cellulose, a major constituent of plant cell walls, consists
of long linear chains of glucose with b(1→4) linkages.
Every other glucose is flipped over, due to b 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.
See: Botany online website; Schematic of arrangement of
website at Georgia Tech. cellulose chains in a microfibril.
 CH2OH 6CH OH CH2OH CH2OH CH2OH
2
O 5 O O H O H O OH
H H H
H H H H H
OH H 1 O 4 OH H 1 O OH H O OH H O OH H
OH H H H
H 2 H
3
H OH H OH H OH H OH H OH
cellulose

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.
Explore and compare structures of amylose & cellulose
using Chime.
 CH2OH
D-glucuronate 6
− H 5 O
6COO H
4 1 O
O H
H 5
H OH H
4 H 1 3 2
OH
H H NHCOCH3
3 2 O
H OH N-acetyl-D-glucosamine
hyaluronate

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.
 CH2OH
D-glucuronate 6
− H 5 O
6COO H
4 1 O
O H
H 5
H OH H
4 H 1 3 2
OH
H H NHCOCH3
3 2 O
H OH N-acetyl-D-glucosamine
hyaluronate

Hyaluronate (hyaluronan) is a glycosaminoglycan with a

repeating disaccharide consisting of 2 glucose derivatives,
glucuronate (glucuronic acid) & N-acetyl-glucosamine.
The glycosidic linkages are b(1→3) & b(1→4).
 heparan sulfate
core glycosaminoglycan
protein

transmembrane
a-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.
Some proteoglycans of the extracellular matrix bind
non-covalently to hyaluronate via protein domains called
link modules. E.g.:
• Multiple copies of the aggrecan proteoglycan associate
with hyaluronate in cartilage to form large complexes.
• Versican, another proteoglycan, binds hyaluronate in
the extracellular matrix of loose connective tissues.
CH2OH
D-glucuronate 6
− H 5 O
Websites on: 6COO H
1 O
4 H
H 5
O
Aggrecan H OH H
4 H 1 3 2
OH
Aggrecan & H H NHCOCH3
2 O
versican. 3
H OH N-acetyl-D-glucosamine
hyaluronate
 iduronate-2-sulfate N-sulfo-glucosamine-6-sulfate
H CH2OSO3−

H O H O H
COO− H
OH H O OH H
H O

H OSO3− H NHSO3−
heparin or heparan sulfate - examples of residues

Heparan sulfate is initially synthesized on a membrane-

embedded 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 N-acetylglucosamine residues may be deacetylated
and/or sulfated.
 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 formation by interacting
with the protein antithrombin.
heparin: (IDS-SGN)5
Heparin has an extended helical
conformation. C O N S

Charge repulsion by the many negatively charged groups

may contribute to this conformation.
Heparin shown has 10 residues, alternating IDS (iduronate-
2-sulfate) & SGN (N-sulfo-glucosamine-6-sulfate).
 heparan sulfate
core glycosaminoglycan
Some cell surface heparan protein
sulfate glycosaminoglycans
remain covalently linked to transmembrane
core proteins embedded in a-helix
the plasma membrane. cytosol

 The core protein of a syndecan heparan sulfate

proteoglycan includes a single transmembrane a-helix,
as in the simplified diagram above.
 The core protein of a glypican heparan sulfate
proteoglycan is attached to the outer surface of the
plasma membrane via covalent linkage to a modified
phosphatidylinositol lipid.
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 iduronate-2-sulfate N-sulfo-glucosamine-6-sulfate
H CH2OSO3−
proteins, e.g.,
O
growth factors. H COO− O H
H
H

OH H O OH H
Diagram H O
by Kirkpatrick
H OSO3− H NHSO3−
& Selleck.
heparin or heparan sulfate - examples of residues
 CH2OH C O

Oligosaccharides H O O CH2 CH
H NH serine
that are covalently OH H residue
attached to proteins OH O H
or to membrane H HN C CH3
lipids may be linear
b-D-N-acetylglucosamine
or branched chains.

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.
 CH2OH C O

H O O CH2 CH
H NH serine
OH H residue
OH O H
H HN C CH3

b-D-N-acetylglucosamine

N-acetylglucosamine (GlcNAc) is a common O-linked

glycosylation of protein serine or threonine residues.
Many cellular proteins, including enzymes & transcription
factors, are regulated by reversible GlcNAc attachment.
Often attachment of GlcNAc to a protein OH alternates
with phosphorylation, with these 2 modifications having
opposite regulatory effects (stimulation or inhibition).
 CH2OH O HN

H O HN C CH2 CH Asn
H
H C O
OH
H HN
OH
HC R X
H HN C CH3
C O
O
N-acetylglucosamine HN

Initial sugar in N-linked HC R Ser or Thr

glycoprotein oligosaccharide C O

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
3-amino acid sequence.
 NAN NAN NAN

Gal Gal Gal

NAG NAG NAG

Man Man N-linked oligosaccharide

Man Key:
NAN = N-acetylneuraminate
NAG Gal = galactose
NAG = N-acetylglucosamine
NAG Fuc
Man = mannose
Fuc = fucose
Asn

Additional monosaccharides are added, and the N-linked

oligosaccharide chain is modified by removal and addition
of residues, to yield a characteristic branched structure.
Many proteins secreted by cells have attached N-linked
oligosaccharide chains.
Genetic diseases have been attributed to deficiency of
particular enzymes involved in synthesizing or modifying
oligosaccharide chains of these glycoproteins.
Such diseases, and gene knockout studies in mice, have
been used to define pathways of modification of
oligosaccharide chains of glycoproteins and glycolipids.
Carbohydrate chains of plasma membrane glycoproteins
and glycolipids usually face the outside of the cell.
They have roles in cell-cell interaction and signaling, and
in forming a protective layer on the surface of some cells.
Lectins are glycoproteins that recognize and bind to
specific oligosaccharides.
Concanavalin A & wheat germ agglutinin are plant
lectins that have been useful research tools.
The C-type lectin-like domain is a Ca++-binding
carbohydrate recognition domain in many animal lectins.
Recognition/binding of CHO 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.
Examples of animal lectins:
Mannan-binding lectin (MBL) is a glycoprotein found
in blood plasma.
It binds cell surface carbohydrates of disease-causing
microorganisms & promotes phagocytosis of these
organisms as part of the immune response.
 selectin
Selectins are integral proteins lectin domain
of mammalian cell plasma
membranes with roles in
cell-cell recognition & binding. outside
The C-type lectin-like domain transmembrane
a-helix
is at the end of a multi-domain
cytosol cytoskeleton
extracellular segment extending
binding domain
out from the cell surface.
A cleavage site just outside the transmembrane a-helix
provides a mechanism for regulated release of some lectins
from the cell surface.
A cytosolic domain participates in regulated interaction
with the actin cytoskeleton.