Heteropolysaccharides: Structure and

Function

Prof. Dr. Özlem Dalmızrak

Near East University, Faculty of Medicine, Department of

Medical Biochemistry

Prepared by Professor İzzet Hamdi ÖĞÜŞ

 Disaccharides
• Disaccharides consist of two monosaccharides joined
covalently by an O-glycosidic bond, which is formed when a
hydroxyl group of one sugar reacts with the anomeric
carbon of the other.
• This reaction represents the formation of an acetal from a
hemiacetal (such as glucopyranose) and an alcohol
(a hydroxyl group of the second sugar molecule).
• Glycosidic bonds are readily hydrolyzed by acid but resist
cleavage by base. Thus disaccharides can be hydrolyzed to
yield their free monosaccharide components by boiling with
dilute acid.
• N-glycosyl bonds join the anomeric carbon of a sugar to a
nitrogen atom in glycoproteins and nucleotides.
Disaccharides
Disaccharides
 POLYSACCHARIDES
Homopolysaccharides contain only a single type of monomer;
Heteropolysaccharides contain two or more different kinds.
 FUNCTIONS OF POLYSACCHARIDES
• Some homopolysaccharides serve as storage forms of
monosaccharides that are used as fuels; starch and glycogen are
homopolysaccharides of this type.
• Homopolysaccharides like cellulose and chitin, for example serve
as structural elements in plant cell walls and animal exoskeletons.
• Heteropolysaccharides provide extracellular support for
organisms of all kingdoms. For example, the rigid layer of the
bacterial cell envelope (the peptidoglycan) is composed in part of
a heteropolysaccharide built from two alternating mono-
saccharide units.
• In animal tissues, the extracellular space is occupied by several
types of heteropolysaccharides, which form a matrix that holds
individual cells together and provides protection, shape, and
support to cells, tissues, and organs.
 Starch
• Starch contains two types of glucose polymer, amylose and
amylopectin.
• The amylose consists of long, unbranched chains of D-glucose
residues connected by (1-4) linkages. Such chains vary in
molecular weight from a few thousand to more than a million.
• Amylopectin also has a high molecular weight (up to 100 million)
but unlike amylose is highly branched. The glycosidic linkages
joining successive glucose residues in amylopectin chains are
( 1-4); the branch points (occurring every 24 to 30 residues) are
( 1-6) linkages.
 Glycogen
• Glycogen is the main storage polysaccharide of animal cells.
• Like amylopectin, glycogen is a polymer of (1-4)-linked subunits of
glucose, with (1-6)-linked branches, but glycogen is more
extensively branched (on average, every 8 to 12 residues) and more
compact than starch.
• Glycogen is especially abundant in the liver, where it may constitute
as much as 7% of the wet weight; it is also present in skeletal
muscle. In hepatocytes glycogen is found in large granules
Glycogen
Glycogen

Glycogen
 Cellulose
• Cellulose, a fibrous, tough, water-
insoluble substance, is found in the
cell walls of plants, particularly in
stalks, stems, trunks, and all the
woody portions of the plant body.
Cellulose constitutes much of the
mass of wood, and cotton is almost
pure cellulose. (1-4) glycosidic bonds
• Like amylose, the cellulose molecule is a linear, unbranched
homopolysaccharide, consisting of 10,000 to 15,000 D-glucose units.
But there is a very important difference: in cellulose the glucose
residues have the -configuration), whereas in amylose, amylopectin,
and glycogen the glucose is in the -configuration.
 Chitin
Chitin is a linear homopolysaccharide like cellulose, but composed of
N-acetylglucosamine residues in (1-4) linkage. The only chemical
difference from cellulose is the replacement of the hydroxyl group at C-
2 with an acetylated amino group. Chitin forms extended fibers similar
to those of cellulose, and like cellulose cannot be digested by
vertebrates. Chitin is the principal component of the hard exoskeletons
of nearly a million species of arthropods—insects, lobsters, and crabs,
for example— and is probably the second most abundant
polysaccharide, next to cellulose, in nature.
 Dextrans
• Dextrans are bacterial and yeast polysaccharides made up
of (a1-6)-linked poly-D-glucose; all have (a1-3) branches,
and some also have (a1-2) or (a1-4) branches.
• Dental plaque, formed by bacteria growing on the surface of
teeth, is rich in dextrans.
• Synthetic dextrans are used in several commercial products
(for example, Sephadex) that serve in the fractionation of
proteins by size-exclusion chromatography.
• The dextrans in these products are chemically cross-linked
to form insoluble materials of various porosities, admitting
macromolecules of various sizes.
 Folding of Homopolysaccharides
• Polysaccharides form three-dimensional macromolecular structures that
are stabilized by weak interactions within or between molecules:
hydrogen bond, hydrophobic, and van der Waals interactions, and, for
polymers with charged subunits, electrostatic interactions.
• The most stable three-dimensional structure for starch and glycogen is a
tightly coiled helix, stabilized by interchain hydrogen bonds. For
amylose, the core of the helix is of precisely the right dimensions to
accommodate iodine and this interaction with iodine is a common
qualitative test for amylose (Iodine solution gives an intense blue color
with starch).
 Agarose
Certain marine red algae, including some of the seaweeds,
have cell walls that contain agar, a mixture of sulfated
heteropolysaccharides made up of D-galactose and an
L-galactose derivative ether-linked between C-3 and C-6.
The two major components of agar are the unbranched
polymer agarose (Mr ~120,000) and a branched component,
agaropectin. The remarkable gel-forming property of agarose
makes it useful in the biochemistry laboratory.
 Glycosaminoglycans

• The extracellular space in the tissues of multicellular

animals is filled with a gel-like material, the
extracellular matrix (ECM), which holds the cells
together and provides a porous pathway for the
diffusion of nutrients and oxygen to individual cells.
• The extracellular matrix is composed of an
interlocking meshwork of heteropolysaccharides and
fibrous proteins such as collagen, elastin, fibronectin,
and laminin.
 Glycosaminoglycans
• Glycosaminoglycans, are a family of linear polymers
composed of repeating disaccharide units. One of
the two monosaccharides is always either N-
acetylglucosamine or N-acetylgalactosamine; the
other is in most cases a uronic acid, usually D-
glucuronic or L-iduronic acid.
• Insome glycosaminoglycans, one or more of the
hydroxyls of the amino sugar are esterified with
sulfate.
• Glycosaminoglycans are attached to extracellular
proteins to form proteoglycans.
 Glycosaminoglycan Repeating disaccharide
Hyaluronate

Number of
disaccharides per chain

~ 50 000

Hyaluronic acid (hyaluronate at physiological pH) contains alternating

residues of D-glucuronic acid and N-acetylglucosamine, with up to
50,000 repeats of the basic disaccharide unit, hyaluronates have
molecular weights greater than 1 million; they form clear, highly viscous
solutions that serve as lubricants in the synovial fluid of joints.
Hyaluronate is also an essential component of the extracellular matrix
of cartilage and tendons, to which it contributes strength and elasticity
as a result of its strong interactions with other components of the
matrix.
 Glycosaminoglycans
• Hyaluronidase, an enzyme secreted by some
pathogenic bacteria, can hydrolyze the glycosidic
linkages of hyaluronate, rendering tissues more
susceptible to bacterial invasion.
• In many organisms, a similar enzyme in sperm
hydrolyzes an outer glycosaminoglycan coat
around the ovum, allowing sperm penetration.
 Glycosaminoglycans
Glycosaminoglycan Repeating disaccharide
Chondroitin
4-sulfate
Number of
disaccharides per chain

20 - 60

Other glycosaminoglycans differ from hyaluronate in two

respects:
1. They are generally much shorter polymers and 2. they are
covalently linked to specific proteins (proteoglycans).
Chondroitin sulfate contributes to the tensile strength of
cartilage, tendons, ligaments, and the walls of the aorta.
 Glycosaminoglycans
Glycosaminoglycan Repeating disaccharide
Keratan sulfate

Number of
disaccharides per chain

~ 25

• Dermatan sulfate contributes to the pliability of skin and is also

present in blood vessels and heart valves. In this polymer, many of the
glucuronate (GlcA) residues present in chondroitin sulfate are replaced
by their epimer, iduronate (IdoA).

• Keratan sulfates have no uronic acid and their sulfate content is

variable. They are present in cornea, cartilage, bone, and a variety of
horny structures formed of dead cells: horn, hair, hoofs, nails, and claws.
 Glycosaminoglycans
Glycosaminoglycan Repeating disaccharide

Heparin

Number of
disaccharides per chain

15 – 90

• Heparin is a natural anticoagulant made in mast cells (a type of leukocyte)

and released into the blood, where it inhibits blood coagulation by binding
to the protein antithrombin. Heparin binding causes antithrombin to bind
to and inhibit thrombin, a protease essential to blood clotting. The
interaction is strongly electrostatic; heparin has the highest negative
charge density of any known biological macromolecule.
• Purified heparin is routinely added to blood samples obtained for clinical
analysis, and to blood donated for transfusion, to prevent clotting.
 GLYCOCONJUGATES
Proteoglycans, Glycoproteins, and Glycolipids
• In addition to their important roles as stored fuels (starch,
glycogen, dextran) and as structural materials (cellulose, chitin,
peptidoglycans), polysaccharides and oligosaccharides are
information carriers: they serve as destination labels for some
proteins and as mediators of specific cell-cell interactions and
interactions between cells and the extracellular matrix.
• Specific carbohydrate containing molecules act in cell-cell
recognition and adhesion, cell migration during development,
blood clotting, the immune response, and wound healing.
• In most of these cases, the informational carbohydrate is
covalently joined to a protein or a lipid to form a glycoconjugate,
which is the biologically active molecule.
Bacterial Cell Wall : Peptidoglycan
 Bacterial Cell Wall : Peptidoglycan
• The rigid component of bacterial cell walls is a heteropolymer of
alternating (1-4)-linked N-acetylglucosamine and N-acetylmuramic acid
residues.
• The linear polymers lie side by side in the cell wall, crosslinked by short
peptides, the exact structure of which depends on the bacterial species.
• The peptide cross-links weld the polysaccharide chains into a strong
sheath that envelops the entire cell and prevents cellular swelling and
lysis due to the osmotic entry of water.
• The enzyme lysozyme kills bacteria by hydrolyzing the (1-4) glycosidic
bond between N-acetylglucosamine and N-acetylmuramic acid.
• Lysozyme is notably present in tears, presumably as a defense against
bacterial infections of the eye.
• Penicillin and related antibiotics kill bacteria by preventing synthesis of
the cross-links, leaving the cell wall too weak to resist osmotic lysis.
PROTEOGLYCAN – An ECM Macromolecule

• Proteoglycans are macromolecules of the cell surface or

extracellular matrix (ECM) in which one or more
glycosaminoglycan chains are joined covalently to a membrane
protein or a secreted protein.
• Proteoglycans are major components of connective tissue such
as cartilage, in which their many noncovalent interactions with
other proteoglycans, proteins, and glycosaminoglycans provide
strength and resilience.
PROTEOGLYCAN – An ECM Macromolecule
 PROTEOGLYCAN – An ECM Macromolecule

Some proteoglycans can form proteoglycan aggregates, enormous

supramolecular assemblies of many core proteins all bound to single
molecule of hyaluronan.
Interactions between cells and extracellular matrix
 Glycoproteins
• Glycoproteins are carbohydrate-protein conjugates in
which the glycans are smaller, branched, and more
structurally diverse than the glycosaminoglycans of
proteoglycans.
• They are found on the outer face of the plasma
membrane, in the extracellular matrix, and in the blood.
• Inside cells they are found in specific organelles such as
Golgi complexes, secretory granules, and lysosomes. The
oligosaccharide portions of glycoproteins are less complex
than the glycosaminoglycan chains of proteoglycans.
• Glycoproteins are rich in information, forming highly
specific sites for recognition and high-affinity binding by
other proteins.
Oligosaccharide linkages in glycoproteins
Bacterial lipopolysaccharides

Glycolipids are
membrane lipids in
which the
hydrophilic head
groups are
oligosaccharides.
As in glycoproteins,
they act as specific
sites for recognition
by carbohydrate-
binding proteins.
 Glycolipids
• Glycolipids are involved in
intercellular
communication.
• Oligosaccharides of
identical composition are
present in both the
glycolipids and
glycoproteins associated
with the cell membrane,
where they serve as cell
recognition factors.
• For example, carbohydrate
residues in these
oligosaccharides are the
antigens of the ABO blood
group substances
 Carbohydrate-Protein Interaction
• Lectins,found in all organisms, are proteins that bind
carbohydrates with high affinity and specificity.
• Lectins serve in a wide variety of
– cell-cell recognition,
– signaling, and
– adhesion processes and
– in intracellular targeting of newly synthesized proteins.
• The adhesion of bacterial and viral pathogens to their animal-
cell targets occurs through binding of lectins in the pathogens to
oligosaccharides in the target cell surface.
• Selectins are plasma membrane lectins that bind carbohydrate
chains in the extracellular matrix or on the surfaces of other
cells, thereby mediating the flow of information between cell
and matrix or between cells.
Role of lectin-ligand interactions in lymphocyte movement to
the site of an infection or injury.
Roles of oligosaccharides in recognition and
adhesion at the cell surface