Molecular Biochemistry

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
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
 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
 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
C O + R' OH R' O C OH
react with an
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

as the ketone or HO
3
C H D-glucose
aldehyde reacts H C OH (linear form)
4
with a distal OH. H C OH
5
Glucose forms an 6
CH2OH
intra-molecular 6 CH2OH 6 CH2OH
hemiacetal, as the 5 5
H O H H O OH
C1 aldehyde & H H
1
C5 OH react, to 4 OH H 1 4 OH H

form a 6-member OH
3 2
OH OH
3 2
H

pyranose ring, H OH H OH
named after pyran. -D-glucose -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
4 5 H HO 2

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

D-fructose (linear) -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.
 6 CH 2 OH 6 CH 2 OH
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
-D -glucose -D -glucose

Cyclization of glucose produces a new asymmetric center

at C1. The 2 stereoisomers are called anomers,  & .
Haworth projections represent the cyclic sugars as having
essentially planar rings, with the OH at the anomeric C1:
 (OH below the ring)
  (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

-D-glucopyranose -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
CH 2OH 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
CH 2OH CH 2OH

H O H H O H
H H
OH H OH H

OH OH OH O OH
H NH 2 H N C CH 3
H
-D-glucosamine -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 H 2O H O
HO HO
HO H + CH 3 -O H HO H
H OH H OH
H OH H O CH 3
-D-glucopyranose methanol methyl--D-glucopyranose
 6 CH 2 O H 6 CH 2 O H

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, is OH 3 2
O
3 2
OH

a disaccharide with H OH m altose H OH

(1 4) glycosidic
link between the C1 6 CH 2 O H 6 CH
2O H
5 O O
OH & C4 OH of 2
5 OH
H H
H H
glucoses. 4
OH H 1 O 4
OH H 1

H
It is the  anomer OH 3 2 3 2
H

(C1 O points down). H OH

cellobiose
H OH

Cellobiose, a product of cellulose breakdown, is the

otherwise equivalent  anomer (O on C1 points up).
The (1 4) glycosidic linkage is represented as a zig-zag,
but one glucose is actually flipped over relative to the other.
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  (O points down from ring), the linkage is (12).
The full name of sucrose is -D-glucopyranosyl-(12)-
-D-fructopyranose.)
 Lactose, milk sugar, is composed of galactose & glucose,
with (14) linkage from the anomeric OH of
galactose. Its full name is -D-galactopyranosyl-(1 4)-
-D-glucopyranose
 Polysaccharides
CH 2 OH 6 CH OH CH 2 OH CH 2 OH CH 2 OH
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
a m y lo s e

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 (14) linkages. It
adopts a helical conformation.
The end of the polysaccharide with an anomeric C1 not
involved in a glycosidic bond is called the reducing end.
 CH 2 OH CH 2 OH
H O H H O H amylopectin
H H
OH H OH H 1
O
OH
O
H OH H OH

CH 2OH CH 2 OH 6 CH 2 CH 2 OH 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 (14)

linkages, but it also has branches formed by (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.
 CH 2 OH CH 2 OH
H O O
glycogen
H H H
H H
OH H OH H 1
O
OH
O
H OH H OH

CH 2 OH CH 2 OH 6 CH 2 CH 2 OH CH 2 OH
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
3 2
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 (16) branches.
The highly branched structure permits rapid release of
glucose from glycogen stores, e.g., in muscle during
exercise. The ability to rapidly mobilize glucose is more
essential to animals than to plants.
 CH 2 OH 6 CH OH CH 2 OH CH 2 OH CH 2 OH
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
c e llu lo s e
Cellulose, a major constituent of plant cell walls, consists of
long linear chains of glucose with (14) linkages.
Every other glucose is flipped over, due to the  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 called microfibrils.
Schematic of arrangement of
Botany online website cellulose chains in a microfibril.
 CH 2 OH 6 CH OH CH 2 OH CH 2 OH CH 2 OH
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
c e llu lo s e

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.
 CH 2 O H
D -glucuronate 6
 H 5 O
6 COO H
4 1 O
O H
H 5
H OH H
4 H 1 3 2
OH
H H NH COCH 3
3 2 O
H OH N -acetyl- D -glucosam ine
hyaluronate

Glycosaminoglycans (mucopolysaccharides) are

polymers of repeating disaccharides.
Within the disaccharides, the sugars 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.
 CH 2 O H
D -glucuronate 6
 H 5 O
6 COO H
4 1 O
O H
H 5
H OH H
4 H 1 3 2
OH
H H NH COCH 3
3 2 O
H OH N -acetyl- D -glucosam ine
hyaluronate

Hyaluronate is a glycosaminoglycan with a repeating

disaccharide consisting of 2 glucose derivatives,
glucuronate (glucuronic acid) & N-acetyl-glucosamine.
The glycosidic linkages are (13) & (14).
 CH 2 O H
D -glucuronate 6
 H 5 O
6 COO H
4 1 O
O H
H 5
H OH H
4 H 1 3 2
OH
H H NH COCH 3
3 2 O
H OH N -acetyl- D -glucosam ine
hyaluronate

When covalently linked to specific core proteins,

glycosaminoglycans form complexes called
proteoglycans. 
Some proteoglycans of the extracellular matrix in turn
link non-covalently to hyaluronate via protein domains
called link modules.
 CH 2 O H
D -glucuronate 6
 H 5 O
6 COO H
4 1 O
O H
H 5
H OH H
4 H 1 3 2
OH
H H NH COCH 3
3 2 O
H OH N -acetyl- D -glucosam ine
hyaluronate

For example, in cartilage multiple copies of the aggrecan

proteoglycan bind to an extended hyaluronate backbone to
form a large complex.
Versican, another proteoglycan that binds to hyaluronate,
is in the extracellular matrix of loose connective tissues.
See web sites on aggrecan and aggrecan plus versican.
 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 a sulfated sugar called iduronic acid,
while N-acetylglucosamine residues may be deacetylated
and/or sulfated.
 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

Heparin, a glycosaminoglycan found in granules of

mast cells, has a structure similar to that of heparan
sulfates, but is relatively highly sulfated.
 heparan sulfate
core glycosaminoglycan
protein

transmembrane
-helix
cytosol

Some cell surface heparan sulfate glycosaminoglycans

remain covalently linked to core proteins embedded in
the plasma membrane.
Proteins involved in signaling & adhesion at the cell
surface have been identified that recognize and bind
segments of heparan sulfate chains having particular
patterns of sulfation.
 CH2OH C O

Oligosaccharides H O O CH2 CH
H serine
that are covalently OH H
NH
residue
attached to proteins OH O H
or to membrane H HN C CH3
lipids may be linear
-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 and
interaction.
 CH2OH C O

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

-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 and wheat germ agglutinin are
plant lectins that have been useful research tools. 
 Mannan-binding lectin (MBL) is a glycoprotein
found in blood plasma.
It associates with cell surface carbohydrates of
disease-causing microorganisms, promoting
phagocytosis of these organisms as part of the
immune response.
 selectin
lectin domain

outside
transmembrane
-helix
cytosol cytoskeleton
binding domain

 Selectins are integral proteins of the plasma membrane

with lectin-like domains that protrude on the outer
surface of mammalian cells.
Selectins participate in cell-cell recognition & binding.