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
The two families of monosaccharides are aldoses and ketoses

Representative
monosaccharides
 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).
 Monosaccharides have asymmetric centers

Three ways to represent the two stereoisomers of glyceraldehyde

 Epimers
(two sugars that differ only in the configuration around one carbon atom)
Formation of hemiacetals and hemiketals
 Formation of the two cyclic
forms of D-glucose

Isomeric forms of monosaccharides that differ

only in the configuration about the hemiacetal
or hemiketal carbon atom are called anomers.

The  and  anomes of D-glucose

interconvert in aqueous solution by
a process called mutarotation.
Pyranoses
and
furanoses
Conformational
formulas of
pyranoses
 Sugars as reducing agents

Glucose and other sugars capable of reducing Cu 2+ are called reducing sugars
 CHO
Pentoses and 1
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
O O
C1 aldehyde & H
H
H H
H
OH

C5 OH react, to 4 OH H 1 4 OH H 1

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 alcohols - lacks an
aldehyde or ketone; e.g., ribitol.
CH2OH

H C OH • Inositol (myoinositol)- formed

from glu 6-P by many diff.
H C OH
organisms
H C OH • Exist in animals as inositol
triphosphate; in plant as
CH2OH
hexophosphoester.
D-ribitol • IP3 in animals is generated
from membrane-bound
• Glycerol- phospholipids and participates
gluconeogenic in the intracellular Ca+2
second messenger system.
precursor in the liver
 Sugar Acids
• sugar acid - the
aldehyde at C1, or
OH at C6, is H
COOH

C OH H
CHO

C OH

oxidized to a HO

H
C

C
H

OH
HO

H
C

C OH
H

carboxylic acid; H C OH

CH 2OH
H C

COOH
OH

e.g., gluconic acid, D -gluconic acid D -glucuronic 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
 Disaccharides contain a glycosidic bond

anomeric carbon

Formation
of
maltose

The glycosidic bond protects the

anomeric carbon from oxidation.

Glu(1→4)Glu
 Some common disaccharides

reducing sugar non reducing sugar non reducing sugar

Non reducing sugars are
named as glycosides.
Glc(1→2)Fru

configuration of
the anomeric carbons joined by
The glycosidic bond
Carbon
 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 OH 3 2
O
3 2
OH

(e.g., amylose), is a H OH m altose H OH

disaccharide with an
(1 4) glycosidic 6 CH 2 O H 6 CH
2O H
5
link between C1 - C4 O O
5 OH
H H
H H
OH of 2 glucoses. 4
OH H 1 O 4
OH H 1

H H
It is the  anomer OH 3 2 3 2

(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
(also called Glycans)

Most carbohydrates
und in nature occur
s polysaccharides.
 Some homopolysaccharides are stored forms of fuel

Electron micrographs of starch and glycogen granules

Other homopolysaccharides (e.g. cellulose and chitin) serve as structural

elements in plant cell walls and animal exoskeletons.
 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

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 (14) linkages.
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.
Amylose and amylopectin, the polysaccharides of starch

occurs every
24 to 30 residues

Strands of amylopectin form double heli

amylopectin structures with each other or with amylose s
 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 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.
 Some homopolysaccharides serve structural roles
The structure of cellulose
(linear, unbranched homopolysaccharide)
Cellulose breakdown by wood fun

Most animals cannot use cellulose

as a fuel source, because they lack
an enzyme to hydrolyze the 1→4
linkage.
 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  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.
 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.
 Chitin
• Identical to cellulose
• Structural polymer – N-acetyl D-
glucosamine
• Found in fish scales, shells of mollusks,
crustaceans, beetles, spider and other
insects
 A short segment of chitin
(linear homopolysaccharide composed of N-acetylglucosamine residues in  linkage)

June beetle
(exoskeleton of chitin)
 Bacterial and algal cell walls contain structural heteropolysaccharides

Peptidoglycan
(alternating 1→4-linked GlcNac-Mur2Ac crosslinked by short peptides)

exact structure depends

on the bacterial species
me kills bacteria by hydrolyzing the 1→4 bond.

The structure of agarose

 Repeating units of some common glycosaminoglycans of extracellular matrix
linear polymers composed of
repeating disaccharide units

Glucoronic acid
N-Acetylglucosamine
 Connective Tissues and
Polysaccharides
• Blood vessels, cartilages and tendons
• Contain protein fibers embedded in a syrupy
matrix containing unbranched
polysaccharides (mucopolysaccharides)
• Tendons- gel-like mixture of polysaccharides
with water serve as lubricants and shock
absorbers around joints and in extracellular
spaces.
 Chondroitin 6-sulfate
• Tendons and cartilages
• Linked to protein
• Has been used in artificial skin
• With glucuronic acid and glucosamine
sulfate- dietary supplements- promoted as
cure for osteoarthritis (due to deterioration
of cartilage at joints)
 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 linear polymers of
repeating disaccharides (Slime-like consistency)
The constituent monosaccharides tend to be modified, with acidic
groups, amino groups, sulfated hydroxyl and amino groups, etc.
-acidic heteropolysaccharides (highly hydrated, gel-like sticky
material due to the negative charge)
-proteoglycans (properties are due more to the CHO than the
protein
 Major types of acidic
heteropolysaccharides
• Hyaluronic acid
• Chondroitin 4-sulfate
• Chondroitin 6-sulfate
• Dermatan sulfate
• Heparin
• Heparan sulfate
• Possess similar repeating disaccharide (glucuronic
acid, N-acetyl-D-glucosamine, D-galactose, etc.)
 CH 2 O H
D -g lu cu ro n ate 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 -g lu co sam in e
hyaluronate
Hyaluronate (hyaluronan) - a glycosaminoglycan with a repeating
disaccharide consisting of 2 glucose derivatives, glucuronate
(glucuronic acid) & N-acetyl-glucosamine.
-synovial fluid- lubricates joints and found in eyes.
•Biological cement filling the intercellular spaces
•A gel-like network acting as a biological filter retaining
microbiotic and other large molecules invading the organisms
The glycosidic linkages are (13) & (14).
• Dermatan sulfate- found in the aorta and
possess anticoagulant property
• Keratan sulfate- cornea and bound to a
protein
 heparan sulfate
core glycosaminoglycan
protein

transmembrane
-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.

CH 2 O H
D -glucuronate 6
H 5 O
Websites on: 6 COO

H
4 1 O
O H
H
Aggrecan H
5
OH H
4 H 1 3 2
OH
Aggrecan & H H NH COCH 3
O
versican. 3 2
H OH N -acetyl- D -glucosam ine
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 -helix
the plasma membrane. cytosol

 The core protein of a syndecan heparan sulfate

proteoglycan includes a single transmembrane -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
CH2OSO3
proteins, e.g., H
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 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,
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

-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
-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 -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.
Proteoglycans are glycosaminoglycan-containing macromolecules
of the cell surface and extracellular matrix

Proteoglycan structure
 Two families of membrane proteoglycans

Mammalian cells have

at least 30 types
of proteoglycans.

Basic unit: a core protein

with covalently attached
glycosaminoglycan(s).

Heparan sulfate bind a variety of extracellular

ligands and thereby modulate the ligands interactio
Four types of protein interactions with NS domains of heparan sulfate
 Some proteoglycans can form proteoglycan aggregates

Aggrecan interacts strongly with

collagen in the extracellular
matrix of cartilage, contributing
to the development and tensile
strength of this connective tissue

Proteoglycan aggregate of the extracellular matrix

Interactions between cells
and the extracellular matrix

Cross-linked meshwork
that gives the whole
extracellular matrix strength
and resilience
Glycoproteins have covalently attached oligosaccharides

oligosaccharide linkages in glycoproteins

Bacterial lipopolysaccharides

Principal determinant
of the serotype
(immunological reactivity)
of the bacterium

Lipopolysaccharide of the outer

membrane of Salmonella typhimurium
Role of lectin-ligand interactions
in lymphocyte movement to the
site of an infection or injury
 An ulcer in the making

Helicobacter pylori
cells adhering to the
gastric surface

This bacterium causes ulcers by interactions between a bacterial

surface lectin and the Leb oligosaccharide of the gastric epithelium.
Lectin-carbohydrate interactions are highly specific and often polyvalent

Details of a lectin-carbohydrate interaction

 Roles of
oligosaccharides
in recognition
and adhesion
at the cell surface
Hydrophobic interactions in sugar residues

Galactose