Detailed polysaccharides slide

1. POLYSACCHARIDES
Presented by
Dr. Sanghita ghosh
2nd year Biochemistry pg
GMC,Nalgonda

2. Objectives :
● Polysaccharides definition and types.
● Homopolysaccharides
● Diseases related with homopolysaccharides
● Heteropolysaccharides
● Diseases related with heteropolysaccharides
● Action of heparin as a blood anticoagulant
● Gag synthesis and degradation
● Proteoglycans
● Disease related with proteoglycans
● Polysaccharide analysis
● Application of polysaccharides

4. POLYSACCHARIDES / GLYCANS:
● Monosaccharide units linked by glycosidic bonds.
● Types:
● Homopolysaccharides/Homoglycans - Single monosaccharide unit.
E.g.- Starch,glycogen and cellulose.
● Heteropolysaccharides/Heteroglycans/Mucopolysaccharides - 2 or more different
monosaccharide units.
E.g.- Hyaluronic acid, chondroitin sulfate.

6. ● Based on their function :
● Structural polysaccharides - Present in cell walls and provides rigidity to cells.
E.g. - Cellulose, Hemicellulose
● Storage polysaccharides - Act as reserve food material.
E.g. - Starch, Glycogen

7. HOMOPOLYSACCHARIDES/HOMOGLYCANS :
Starch -
● Reserve carbohydrate of plant .
● Sources : Potatoes, Tapioca, Cereals ( rice and wheat)
● Composition : Amylose : Alpha 1,4 glycosidic linkages
Amylopectin : Alpha 1,6 glycosidic linkages

10. ● Digestion :
1. Begins in mouth by salivary amylase, which hydrolyzes the alpha 1,4 glycosidic
linkages.
2. In small intestine, under the influence of pancreatic amylase, starch is degraded into
mixture of small oligosaccharides.
3. Further hydrolysis by an alpha- glucosidase,which removes 1 glucose residue at a
time.
4. Debranching enzyme hydrolyzes alpha 1,4 and 1,6 linkages, producing
monosaccharides absorbed by intestine and transported to bloodstream.

11. Glycogen -
● Reserve carbohydrate in animals.
● Storage - Liver and muscle
● Sources - Bananas, apples and oranges.
● Composition - Strongly branched polymer of alpha D- glucose primarily of alpha 1,4
linkages and 1,6 linkages.
● Glycogenin - Innermost core of glycogen contains a protein which acts as primer for
glycogen synthesis.
● Use - Maintain physiological blood
glucose concentration.

13. ● Glycogen store fluctuation -
1. Increases during well fed state.
2. Depleted during fasting state.
3. Moderately decreased during prolonged fasting.
4. Glycogen synthesis and degradation go on continuously.

14. Cellulose -
● Supporting tissues of plants.
● Storage -Stem, stalks, trunks and woody portions of plant body.
● Sources - Cotton, flax,bamboo, jute
● Composition - Glucose units combined with beta 1,4 - linkages.
Straight line structure with no branching points.
● M/W : 2-5 million.

16. ● Digestion -
Beta 1,4 bridges are hydrolyzed by enzyme cellobiase.
But this enzyme is absent in animal and human digestive system.

17. Difference between starch,glycogen and cellulose

18. Inulin -
● Long chain homoglycan
● Storage : Directly stored as glycogen like sugars or starch.
● Sources: Dahlia, Onion, Garlic, Dandelion
● Composition : D-fructose units with repeating beta 1,2- linkages.
● Use : Assess the renal clearance and glomerular filtration rate in patients

19. ● Digestion :
Body doesn’t have digestive enzymes to break down inulin.
Instead, it goes through digestive system to large intestine where it nourishes the gut
bacteria .

20. Dextran -
● Bacterial and yeast polysaccharide.
● Composition : Highly branched homopolymers of glucose units 1-6, 1-4 and 1-3
linkages.
● M.W : 1 - 4 million
● Use : Intravenous as plasma volume expanders for treatment of hypovolemic shock.
Fractionation of proteins by chromatography.

21. Chitin :
● Linear homopolysaccharide
● Principal component of hard exoskeleton of arthropods- insects,lobsters and crabs.
● Storage - Bonded to glucans in fungal cell walls.
● Composition - Beta 1,4 glycosidic linkages.
● Use - Tissue engineering, wound healing, stem cell technology and non - absorbable
sutures.

22. Diseases related -
GLYCOGEN STORAGE DISEASE :

23. HETEROPOLYSACCHARIDES/HETEROGLYCANS
Agar and agarose -
● Agar is prepared from sea weeds.
● Composition : D- galactose and L- galactose derivative an ether linked between C3 and C6
● Use : Immunodiffusion and immunoelectrophoresis.

24. Hyaluronic acid -
● Also known as hyaluronan or hyaluronate.
● Composition - Repeating units of N-acetyl-glucosamine beta-1,4- glucuronic acid
beta-1-3-N-acetyl glucosamine.
● Present in connective tissues,tendons,synovial fluid and vitreous humour.
● Use : Lubricant in joint cavities.
Hyaluronidase present in sperm hydrolyzes the outer glycosaminoglycans coat
around ovum,allowing sperm penetration.

25. Heparan sulfate -
● Produced by all animal cells and contains sulfated and non sulfated sugars.
● Storage - Liver, lungs and monocytes.
● Composition - Repeating units of sulfated glucosamine - alpha -1,4 - L- iduronic acid .
● Use - Therapeutic agent to inhibit coagulation of blood.

26. Chondroitin sulfate -
● Tensile strength of cartilage, tendons, ligaments, heart valves and walls of aorta.
● Composition - Repeating units of glucuronic acid beta 1,3-N acetyl galactosamine sulfate
beta 1,4 and so on .
● Present in connective tissues,cartilage,bone and tendons.
● Use : Therapeutic intervention in multimodal approach of OA.

27. Keratan sulfate -
● Present in cornea, cartilage,bone .
● Composition : Beta -1,3 linked poly -N-acetyllactosamine with sulfated residues on 6th
positions of both galactose and N-acetylglucosamine.
● Only GAG that doesn’t contain uronic acid.
● Defective sulfation of keratan sulfates causes macular corneal dystrophy .

28. Dermatan sulfate -
● Found in skin,blood vessels,heart valves.
● Composition : L- iduronic acid and N- acetyl galactosamine in beta-1,3 linkages.
● Use : Wound repair, response to infection,regulation of blood coagulation.

29. Pectin :
● Plants don’t produce GAG.
● They produce pectins ,major component of cell wall.
● Composition - Alpha 1,4 linked with galacturonate residues interspersed with hexose
rhamnose.

31. Diseases related :
Mucopolysaccharidoses :
● Hereditary disease.
● 1:25,000 live births.
● Deficiency of lysosomal hydrolases involved in degradation of heparan sulfate and/or
dermatan sulfate.
● Progressive disorder that causes lysosomal accumulation of glycosaminoglycans.
Autosomal recessive except hunter syndrome(x linked).

32. C/F -
● Skeletal deformities.
● ECM deformities.
● Intellectual disability.
● Homozygous children are apparently normal at birth and gradually deteriorate.
Investigations -
● Presence of oligosaccharides in urine.
Diagnosis -
● Measurement of patient’s cellular level of lysosomal hydrolases.
Treatment -
● Bone marrow and cord blood transplants.
● Enzyme replacement therapy.

33. Types :
1.Hurler syndrome (MPS I) -
● Most severe form.
● Alpha - l- iduronidase deficiency
C/F :
● Corneal clouding
● Developmental disability
● Coarse facial features
● Upper airway obstruction
● Hearing loss
● Deposition in coronary artery leads to ischaemia and early death
Treatment :
● Bone marrow/Cord blood transplantation
● Enzyme replacement therapy

34. 2. Hunter syndrome (MPS II) -
● X- linked deficiency
● Iduronate sulfatase deficiency
C/F :
● No corneal clouding.
● Mild to severe physical deformity
● Developmental deformity
Treatment
● Enzyme replacement therapy.
3. Sanfilippo syndrome (MPS III) -
● Type A : Heparan sulfatase deficiency
● Type B : N-Acetylglucosaminidase deficiency
● Type C : Acetyl CoA : alpha glucosaminide-acetyltransferase deficiency
● Type D : N-Acetylglucosamine 6-sulfatase deficiency

35. 4. Morquio syndrome ( MPS IV)
● Deficiency of N-acetylgalactosamine-6-sulfate sulfatase
5. Maroteaux Lamy syndrome ( MPS VI)
● Deficiency of Arylsulfatase.
6. Sly syndrome (MPS VII) -
● Beta glucuronidase deficiency.
C/F :
● Hepatosplenomegaly
● Skeletal deformity
● Short stature
● Corneal clouding
● Developmental disability
7. Natowicz syndrome
● Deficiency of hyaluronidase
● Associated gene is HYAL1

37. Blood grouping system :
● Human ABO blood groups illustrate the effects of glycosyltransferases on formation of
glycoproteins.
● Specific glycosyltransferases add extra monosaccharide to O antigen.
● Each person inherits gene for one glycosyltransferase of this type from each parent.

38. Protein interactions with N-sulfated domains of heparan sulfate :
Action of heparin as a blood anticoagulant -

39. GAG SYNTHESIS :
● Heteropolysaccharide chains are elongated by sequential addition of alternating acidic and
amino sugars by UDP derivatives.
● Reactions are catalyzed by specific glycosyltransferases.
● Synthesis occurs in golgi not in cytosol.

40. ● Amino sugar synthesis -
Amino sugars are components of glycoconjugates such as
1. Proteoglycans
2. Glycoproteins
3. Glycolipids
A. N-Acetylglucosamine and N-Acetylgalactosamine
B. N-Acetylneuraminic acid

41. ● Acidic sugar synthesis :
1. Glucuronic acid

42. 2. L -Iduronic acid : Synthesis of L-iduronic occurs after D-glucuronic has been incorporated
into carbohydrate chain.
● Core protein synthesis : It occurs in RER,enters lumen and
moves to golgi,glycosylated by glycosyltransferases.
● Carbohydrate chain synthesis : Transfer of xylose from
UDP-xylose to hydroxyl group of a serine catalyzed by
xylosyltransferase.
● Sulfate group addition : Sulfation is catalyzed by
sulfotransferases.

43. GAG DEGRADATION :
● GAG are degraded in
Lysosomes.
1. GAG phagocytosis - GAG are
Extracellular and are
engulfed by invagination
of cell membrane forming
a vesicle inside of which
GAG are degraded.
This vesicle then fuses with
lysosome

44. 2. Lysosomal degradation - It requires acid hydrolases for complete digestion.
a. Polysaccharide chains are cleaved by endoglycosidases producing oligosaccharide.
b. Degradation of oligosaccharides occur sequentially from non reducing end of each
chain.

45. PROTEOGLYCANS :
● Proteins + Glycosaminoglycans in ECM aggregate covalently and non covalently to form
proteoglycans.
● Bottle-brush like molecular structure with bristles.
● Bristles consists of core protein to which keratan and chondroitin sulfate are covalently
linked.
● Interaction between core protein and hyaluronate is stabilized by a link protein.
● Oligosaccharides are linked to protein via the amide N of specific Asparagine synthetase
residues known as N-linked oligosaccharide.
● Keratan sulfate and chondroitin sulfate chains are glycosidically linked to
core protein via oligosaccharides that are covalently
bonded to side chain
O atoms of specific serine or threonine residues known
as O- linked oligosaccharides.

46. ● This extended brush like structure
of proteoglycans ,together
with polyanionic character
of their keratan sulfate and
chondroitin sulfate cause these
complexes to form highly
hydrated gels.

47. Defects in synthesis/Degradation of sulfated GAG diseases :
● Scheice syndrome
Defect occurs in degradative enzymes, accumulation of incompletely degraded GAG can
produce disease .
C/F -
Joint stiffening.
Normal intelligence,life span.
Diagnosis -
Increased urinary secretion of heparan and dermatan sulfate by DMB test (1,9-
dimethylmethylene) test.
Electrophoresis
Genetic testing
Treatment -
Enzyme replacement therapy
Hematopoietic stem cell transplantation

48. ● Ehler Danlos syndrome
Mutation in specific biosynthetic enzyme required in chondroitin, heparin,dermatan sulfate
synthesis .
C/F-
Hyperflexible joints,fragile skin,premature ageing
Short stature,skeletal defects, bipolar disorder
Neuropathy,diaphragmatic hernia
Diagnosis -
CT and MRI helps in identification of an aneurysm.
Treatment-
No particular cure.
Physical exercise.
Ibuprofen and acetaminophen to relieve pain.
Surgery to repair joint damage.

49. CARBOHYDRATE ANALYSIS :

50. Application :
● In vaccine - Polysaccharides vaccines are strongly immunogenic protein carriers like
diphtheria and tetanus toxins that induce T-cell dependent response and enhance the
immunogenicity through interacting with immune system.
● Biomedical applications - Polysaccharides obtained from algae have been extensively
used in biomedical applications such as wound management,regenerative medicine and to
control drug delivery. E.g.- Heparin loaded hydrogels
● Drugs,vaccine delivery and tissues engineering .
● Anticoagulant/antithrombotic,antiviral,anti-lipidemic antioxidant activities.
● Polysaccharides in coronavirus - Entry of the virus to the host cell can be interfered by
sulfated polysaccharides by blocking the positive charge of pathogen surface receptors.

51. ● Antitumor and immunomodulatory activities - Natural polysaccharides derived from
mushrooms have shown potent antitumour and pharmaceutical activities. E.g. -
ganoderma lucidum have proved to have potent in vitro immune activation and antitumor
activity on breast cancer cells.
● Antioxidant applications - Polysaccharides derived from plants exhibit strong antioxidant
activities,which protect human body against free radicals. E.g.- hyriopsis cumingii
●

53. REFERENCE :
● Lippincott illustrated reviews of biochemistry
● Lehninger principles of biochemistry
● Voet’s principles of biochemistry
● Vasudevan principles of biochemistry
● Pubmed journals

54. THANK YOU