HETEROPOLYSACCHARIDES

By

Dr Ndagire Dorothy
HETEROPOLYSACCHARIDES

• Are high-molecular-weight carbohydrate polymers

with more than one kind of monosaccharide or
disaccharide units.
• Provide extracellular support for organisms of all
kingdoms.
• Important examples include glycosaminoglycans
(GAGs) – the principle components of proteoglycans
and murein, a major component of bacterial cell walls.
 a) GAGs - high-molecular-weight carbohydrate
polymers
Glycosaminoglycans forming the proteoglycans are
abundant heteropolysaccharides in the body.
They are long unbranched molecules containing a
repeating disaccharide unit.
 Usually one sugar is a uronic acid (either D-
glucuronic or L-iduronic) and the other is either N-
acetylglucosamine (GlcNAc) or N-acetylgalactosamine
(GalNAc).
 One or both sugars contain sulfate groups (the only
exception is hyaluronic acid).
GAGs are highly negatively charged which is essential
for their function.
Types of glycosaminoglycans

iduronic acid with

sulphate+ N-sulfo-D-
glucosamine
THE SPECIFIC GAGs OF PHYSIOLOGICAL
SIGNIFICANCE
1. Hyaluronic acid
Occurence : synovial fluid, ECM ( Extra Cellular
Matrix ) of loose connective tissue

Hyaluronic acid is unique among the GAGs because

it does not contain any sulfate and is not found
covalently attached to proteins.
It forms non-covalently linked complexes with
proteoglycans in the ECM.

Hyaluronic acid polymers are very large (100 -

10,000 kD) and can displace a large volume of water.
Hyaluronic acid (D-glucuronate + GlcNAc)
2.Dermatan sulfate (L-iduronate + GlcNAc sulfate)

Occurence : skin, blood vessels, heart valves

Function of Dermatan sulfate

• Dermatan sulfate (DS) is an abundant

glycosaminoglycan in the extracellular matrix
of the skin as well as in many other tissues. It
is a component of the small leucine-rich
proteoglycan decorin, which binds to
collagen and other matrix molecules and
plays an important role in the structural
integrity of the skin.
3. Chondroitin sulfate (D-glucuronate + GalNAc sulfate)

Occurence : cartilage, bone, heart valves ;

It is the most abundant GAG.
Chondroitin sulfate is
a chemical that is
normally found in
cartilage around joints in
the body. Chondroitin
sulfate is usually
manufactured from
animal sources, such as
shark and cow cartilage.
Chondroitin sulfate is
used for osteoarthritis
treatment.
4. Heparin (iduronic acid with sulphate+ N-sulfo-D-
glucosamine)

Occurence :
Heparin :is an anticoagulant secreted by most cells in the intestinal
mucosa , liver ,lungs ,spleen and kidney.
Heparan sulfate : basement membranes, component of cell surfaces
Function: its an anticoagulant, stimulates the release of
lipoprotein lipase which hydrolyses absorbed fat.
5. Keratan sulfate ( Gal + GlcNAc sulfate)

Occurence : cornea and cartilage ;

It plays a role in corneal transparency
• Keratan sulfates are often aggregated with chondroitin
sulfates.
b) MUREIN (Peptidoglycan)

 A polymer found in the cell walls of prokaryotes that consists of

polysaccharide and peptide chains in a strong molecular network.
Also called mucopeptide , murein .

The sugar component consists of alternating residues of β-(1,4) linked

N-acetylglucosamine and N-acetylmuramic acid residues.

Attached to the N-acetylmuramic acid is a peptide chain of three to five

amino acids.
Peptidoglycan serves a structural role in the bacterial cell wall,
giving the wall shape and structural strength, as well as
counteracting the osmotic pressure of the cytoplasm.

Peptidoglycan is also involved in binary fission during bacterial

cell reproduction.

The peptidoglycan layer is substantially thicker in

Gram-positive bacteria (20 to 80 nm) than in Gram-negative
bacteria (7 to 8 nm)

Peptidoglycan forms around 90% of the dry weight of Gram-

positive bacteria but only 10% of Gram-negative strains.
GLYCOCONJUGATES
Glycoconjugates

They are compounds that result from covalent

linkages of carbohydrate molecules to both proteins
and lipids.
They have a profound effects on the functions of
individual cells as well as cell-cell interactions of
multicellular organisms.
Two classes of carbohydrate-protein conjugate:
glycoproteins and proteoglycans.
The glycolipids (oligosaccharide-containing lipid
molecules) are found predominately on the outer
surface of plasma membrane.
1. Glycoproteins
Glycoprotein carbohydrate chains are highly diverse. They are
formed by glycosylation and classified into two groups:
1. N-linked oligosaccharides
2. O-linked oligosaccharides
The N-linked oligosaccharides have greater than 5 sugar
residues
N-linked attached to polypeptides by an N-glycosidic bond
with a chain amide group of amino acid asparagine
O-linked oligosaccharides are generally short (1-4 sugar
residues)
O-linked are attached to polypeptides by the side chain
hydroxyl group of amino acids serine or threonine in
polypeptide chains or hydroxyl groups of membrane lipids
Glycosylation
• Glycosylation is the process or result of addition of saccharides
to proteins and lipids
• The process plays an important role in the synthesis of
membrane and secreted proteins
• Majority of proteins synthesized in the rough ER undergo
glycosylation
• It is an enzyme -directed site-specific process.
• Two types of glycosylation exist: N-linked glycosylation to the
amide nitrogen of asparagine side chains and O-linked
glycosylation to the hydroxy oxygen of serine and threonine
side chains.
• Glycosylation may play a role in cell-cell adhesion (a
mechanism employed by cells of the immune system), as well.
GLYCOPROTEIN FUNCTIONS
Functions: Many glycoproteins have structural functions:
constituent of the cell wall; form connective tissues such as
collagen; found in gastrointestinal mucus secretions; used as
protective agents and lubricants ;found abundantly in the blood
plasma.

The human blood groups A, B, AB, and O depend on the

oligosaccharide part of the glycoprotein on the surface of
erythrocyte cells. The terminal monosaccharide of the
glycoprotein at the nonreducing end determines blood group.
BLOOD GROUPS

TYPE TERMINAL SUGAR

A N-acetylgalactosamine
B a-D-galactose
AB both the above
O neither of the above
O is the “universal donor”
AB is the “universal acceptor”
Oligosaccharides are antigeneic
determinants
Carbohydrates on cell surfaces are
immunochemical markers.
ABO blood group antigens are oligosaccharide
components of glycoproteins and glycolipids on the
surfaces of individual cells, besides blood cells.
 Individuals with type A cells have A antigens on
their cell surfaces and carry anti-B antibodies
Those with type B cells which bear B antigens,
carry anti-A antibodies
Those with type AB cells, which have both A and B
antigens, carry neither anti-A nor anti-B antibodies
Type O individuals whose cells bear neither antigen,
carry both anti-A and anti-B antibodies.
Transfusion of type A blood group into a type B
individual, results in an anti-A antibody- A antigen
reaction.
This reaction clumps together (agglutinates) the
transfused erythrocytes, resulting in an often fatal
blockage of blood vessels.
Functions of glycoproteins (elaborated)
Carbohydrates and proteins by themselves serve in a vast number
of biological functions,linking the two together results in a
macromolecule with an extremely large number of functions.
Structural: Glycoproteins are found throughout matrices.
They act as receptors on cell surfaces that bring other cells and
proteins together giving strength and support to a extracellular
matrix.
 In nerve tissue glycoproteins are abundant in gray matter and
appear to be associated with synaptosomes, axons, and
microsomes.
Protection: Human lacrimal glands produce a glycoprotein
which protects the corneal epithelium from desiccation and
foreign particles.
Human sweat glands secrete glycoproteins which protect the
skin from the other excretory products that could harm the skin
Functions of glycoproteins
Prothrombin, thrombin, and fibrinogen are all glycoproteins
that play an intricate role in the blood clotting mechanism
In certain bacteria the slime layer that surrounds the
outermost components of cell walls are made up of
glycoproteins of high molecular weight.
 In addition to forming these s-layers, glycoproteins also
function as bacterial flagella.
These are made up of bundles of glycoproteins protruding from
the cell's surface. Their rotation provides propulsion.
In plants, glycoproteins have roles in cell wall formation and
tissue differentiation
Reproduction: Glycoproteins found on the surface of
spermatozoa appear to increase a sperm cell's attraction for
the egg by altering the electrophoretic mobility of the plasma
membrane.
Functions of glycoproteins

• Adhesion: Glycoproteins serve to adhere cells to cells

and cells to substratum.
• Hormones: There are many glycoproteins that
function as hormones such as human chorionic
gonadotropin (HCG) which is present in human
pregnancy urine.
-Another example is erythropoietin which regulates
erythrocyte production
• Enzymes: Glycoprotein enzymes are of three types.
These are oxidoreductases, transferases, and
hydrolases.
 Functions of glycoproteins
Carriers: Glycoproteins can bind to certain molecules and
serve as vehicles of transport. They can bind to vitamins,
hormones, cations, and other substances.
Inhibitors: Many glycoproteins in blood plasma have shown
antiproteolytic activity. For example, the glycoprotein a1-
antichymotrypsin inhibits chymotrypsin.
Immunological: The interaction of blood group substances
with antibodies is determined by the glycoproteins on
erythrocytes. Many immunoglobulins are actually
glycoproteins.
B and T cells contain surface glycoproteins that attract bacteria
to these sites and bind them. In much the same manner,
glycoproteins can direct phagocytosis. Because the HIV virus
recognizes the receptor protein CD4, it binds to helper T cells
which contain it.
CELL MEMBRANE
The cell membrane is a fluid mosaic of lipids, proteins, and
carbohydrates.
Membrane carbohydrates are usually branched
oligosaccharides with fewer than 15 sugar units.
Some of these oligosaccharides are covalently bonded to
lipids, forming molecules called glycolipids.
Most are covalently bonded to proteins, which are thereby
glycoproteins.
Plants produce pectin, major component of cell wall.
The oligosaccharides on the external side of the plasma
membrane vary from species to species
The diversity of the molecules and their location on the cell's
surface enable oligosaccharides to function as markers that
distinguish one cell from another.
THE MOSAIC OF CELL’S MEMBRANE
CELL MEMBRANE MATRIX
The biological membrane is a collage of many
different proteins embedded in the fluid matrix of the
lipid bilayer.

The lipid bilayer is the main fabric of the membrane,

and its structure creates a semi-permeable
membrane.

The hydrophobic core impedes the transport of

hydrophilic structures, such as ions and polar
molecules but enable hydrophobic molecules, which
can dissolve in the membrane, cross it with ease.
2. PROTEOGLYCANS
 Proteoglycans represent a special class of glycoproteins that
are heavily glycosylated.
 They consist of a core protein with one or more covalently
attached glycosaminoglycan chain(s).
 These glycosaminoglycan (GAG) chains are long, linear
carbohydrate polymers that are negatively charged under
physiological conditions, due to the occurrence of sulphate
and uronic acid groups.
 Proteoglycans can be categorised depending upon the nature
of their glycosaminoglycan chains. These chains may be:
1. chondroitin sulfate and dematan sulfate
2. heparin and heparin sulfate
3. keratan sulfate
• Proteoglycans can also be categorised by size and are found in animal
extracellular matrix.
• Example of large proteoglycan is aggrecan.
• Aggrecan, is the major proteoglycan in cartilage, present in many adult
tissues including blood vessels and skin.
SYNTHESIS OF PROTEOGLYCANS
The protein component of proteoglycans is
synthesized by ribosomes and translocated into the
lumen of the rough endoplasmic reticulum.
Glycosylation of the proteoglycan occurs in the
Golgi apparatus in multiple enzymatic steps.
First a special link trisaccharide is attached to a serine
side chain on the core protein to serve as a primer for
polysaccharide growth.
Then sugars are added one at the time by glycosyl
transferase.
The completed proteoglycan is then exported in
secretory vesicles to the extracellular matrix of the
cell.
 Structure of proteoglycans
• The GAGs extend perpendicular from the core protein in a
bottlebrush- like structure.
• The linkage of GAGs such as (heparan sulfates and chondroitin
sulfates) to the protein core involves a specific trisaccharide
linker
• Some forms of keratan sulfates are linked to the protein core
through an N-asparaginyl bond.
• The protein cores of proteoglycans are rich in Ser and Thr
residues which allows multiple GAG attachment.
FUNCTION OF PROTEOGLYCANS
Proteoglycans are a major component of the animal
extracellular matrix, the 'filler' substance existing between cells
in an organism.
Individual functions of proteoglycans can be attributed to
either the protein core or the attached GAG chain.
They are also involved in binding cations (such as sodium,
potassium and calcium) and water, and also regulate the
movement of molecules through the matrix.????
They can affect the activity and stability of proteins and
signalling molecules within the matrix.
Because of high viscosity and low compressibility they are
ideal for a lubricating fluid in the joints.
Effects of poor metabolism of proteoglycans.

• Hurler’s syndrome: (refer notes ) disease related with

proteoglycan metabolism where excessive accumulation
of dermatin sulfate due to deficiency of a specific
enzyme may cause mental retardation, skeletal deformity
and death in early childhood.
3. Glycolipids
• Glycolipids are lipids with a carbohydrate attached by a glycosidic
bond. Their role is to maintain stability of the membrane and to
facilitate cellular recognition. The carbohydrates are found on the
surface of all eukaryotic cell membranes.
SUMMARY
• Monosaccharides, the simplest carbohydrates, are classified as
aldoses or ketoses.
• The cyclic hemiacetal and hemiketal forms of monosacchs have
either alfa or beta configuration at their anomeric carbon.
• Monosacch derivatives include aldonic acids, uronic acids,
deoxy sugars, amino sugars, alfa & beta glycosides.
• Disaccharides simplest polysaccharides occuring as hydrolysis
products of larger molecules e.g. Lactose,sucrose
• Oligosaccharides play important roles in determining protein
structure and in cell-surface recognition phenomena.
Oligosacchs with 3 or more sugar residues are mostly found in
plants.
Summary contd.
• POLYSACCHARIDES consist of monosacchs linked by
glycosidic bonds.
• Cellulose and chitin are structural polysacchrides with
beta(1-4) linkages that adopt rigid and extended
structures.
• The storage polysaccharides starch and glycogen
consist of alfa-glycosidically linked glucose residues
• Glycosaminoglycans are unbranched polysacchs
containing uronic acids and amino sugars that are
often sulfated
Summary contd
• GLYCOCONJUGATES: Proteoglycans &
glycoproteins play important roles in information
transfer in living organisms.

• Proteoglycans are enormous molecules consisting of

hyaluronate with attached core proteins that bear
numerous glycosaminoglycans and oligosaccharides.
Found in the extracellular matrix of tissues

• Bacterial cell walls are made up of peptidoglycan, a

network of polysaccharide and poypeptide chains.
Summary contd
Glycoproteins or Glycosylated proteins may contain
N-linked oligosaccharides attached to Asn (asparagine)
or O-linked oligosacchrides attached to Ser or Thr
(serine or threonine) or both
Different molecules of glycoproteins may contain
different sequences and locations of oligosaccharides.
Occur in cells in both soluble and membrane bound
forms, and in extracellular fluids
 Sample questions
1 ( a ). Define and give examples of Glycosaminoglycans
( GAGs).
( b) state the biological significances of Glycosaminoglycan
2. Name the terminal sugar found in each of the blood
group type: A,B,AB and O.
Difference btn peptidoglycans and
glycoproteins
• Both are proteins containing carbohydrates but they contain
different sugars, Have different structures, perform different
functions and are present in different sites