Glycosaminoglycams+Glycoconjugates (2) final.pptx

Going into the molecules that form the basis of life!

1. Heteropolysaccharides: Glycosaminoglycans and Glycoconjugates

2. Name: Marryam Faiz Roll. No: Z18-15

3. My Panel Areej Ahmad Siddiqua Javed Sarim Hassan Roll. No. Z19-24 Roll. No. Z19-01 Roll. No. Z19-03

4. Contents Polysaccharides Classification Glycosaminoglycans Structure Examples Mucopolysaccharidoses Glycoconjugates Types Glycoproteins Glycolipids Proteoglycans Examples Significance

5. Polysaccharides They are a long polymeric chain of monosaccharide units bound together by glycosidic bonds. These are the most abundant carbohydrates found in food . Homoglycans : contain one monosaccharide unit. e.g. starch, cellulose, glycogen Heteroglycans : contain two or more monosaccharide units. e.g. GAGs, agar, peptidoglycans

6. Heteroglycans (heteropolysaccharides) M ost naturally occurring heteroglycans contain only 2 different monosaccharides and are closely associated with  lipid  or  protein. The major heteropolysaccharides include the connective-tissue polysaccharides the  blood group substances glycoproteins (combinations of carbohydrates and proteins) such as  gamma globulin , glycolipids (combinations of carbohydrates and lipids)

7. Glycosaminoglycans (GAG)

8. What Is Glycosaminoglycan (GAG)? Heteropolysaccharides of the ECM/ground substance. Formerly known as mucopolysaccharides . A type of linear polymer made up of repeating disaccharide units ( two-sugar units ). The repeating two-sugar unit consists of a uronic sugar and an amino sugar (with a few exceptions).

9. Properties Highly negatively charged . Highly polar and attract water. GAGs are hydrophilic molecules capable of absorbing up to 1000 times their volume in water to form gel-like materials. Ocurrence O nly present in animals and bacteria and not in plants .

10. Glycosaminoglycans (GAG)

11. Composition Amino sugar: It comprises of N-Acetylglucosamine or N- acetylgalactosamine Uronic (acidic) sugar: It is made up of D-glucuronic or Liduronic acid or Galactose.

12. Dermatan Sulfate Chondroitin Sulfate hyaluronate Keratan Sulphate Heparan Sulfate Examples

13. Hyaluronate Only GAG that is non-sulphonated. Composed of D-glucuronic acid and N-acetyl-D-glucosamine. Can be 25,000 disaccharide repeats in length. Highly viscous Lubricant and shock absorber Hyaluronidase hydrolyses it and reduces viscosity (spleen and testicular tissues). Occurrence  : synovial fluid, ECM of loose connective tissue, vitreous humor of eye

14. Hyaluronidase Hyaluronidase is an enzyme . It hydrolyses HA and reduces viscosity . It is present in the spleen and testicular tissues. The enzyme is also secreted by some bacteria. It hydrolyzes the glycosidic linkages of hyaluronan. Thus tissues are more susceptible to bacterial invasion.

15. Chondroitin Sulphate A sulfated  glycosaminoglycan  (GAG). C omposed N- acetylgalactosamine ( GalNAc )  and  glucuronic acid ( GlcA ) Most abundant GAG in the body Found in cartilage, ligaments, tendons and aorta Of 2 types , A and B. Binds collagen in cartilage to form a strong network. A widely used  dietary supplement  for treatment of  osteoarthritis .

16. Dermatan Sulphate Composed of N-acetyl galactosamine  ( GalNAc ) and  iduronic acid  ( IdoA ). Greek ‘ derma ’ is ‘ skin .’ Contains small amounts of other carbohydrates. It is also referred to as  chondroitin sulfate B , although it is no longer classified as a form of chondroitin sulfate by most sources. F ound mostly in  skin , but also in  blood vessels ,  heart valves

17. Keratan Sulphate Composed of N-acetyl-glucosamine-6-phosphate and D-galactose. Most common heterogenous GAG. Greek ‘ keras ’ is ‘horn’. Form dead cells like horn, hair nails and claws. F ound especially in the  cornea ,  cartilage , and  bone. Act as a cushion to absorb  mechanical shock.

18. Heparin   Isolated from dog  liver  cells ( hepar  is Greek for " liver ";  hepar  +in). Composed of a  glucuronic acid  ( GlcA ) linked to  N -acetylglucosamine  ( GlcNAc ), typically making up around 50% of the total disaccharide units Serves as an anti-coagulant Heparans have less sulfate groups than heparins . Occurence  : Heparin :arteries of the lungs, liver and skin Heparan sulfate : basement membranes, component of cell surfaces

19. Representative heteropolysaccharides *Covalently linked to protein; the proportion of protein to carbohydrate in such complex molecules varies from about 10% protein in the case of chondroitin-4-sulfate to better than 95% for gamma globulin. heteropolysaccharide component sugars functions distribution hyaluronic acid D-glucuronic acid and  N -acetyl-D-glucosamine lubricant, shock absorber, water binding connective tissue, skin chondroitin-4-sulfate* D-glucuronic acid and  N -acetyl-D-galactosamine-4- O -sulfate calcium accumulation, cartilage and bone formation cartilage heparin* D-glucuronic acid,  L -iduronic acid,  N -sulfo-D-glucosamine anticoagulant mast cells, blood gamma globulin* N -acetyl-hexosamine, D-mannose, D-galactose antibody blood blood group substance* D-glucosamine, D-galactosamine,  L -fucose, D-galactose blood group specificity cell surfaces, especially red blood cells

20. Glycoconjugates

21. Mucopolysaccharidosis A group of  metabolic disorders  caused by the absence or malfunctioning of the 11 lysosomal   enzymes  needed to break down GAGs. Over time, these GAGs collect in the cells, blood and connective tissues. This accumulation affects appearance, physical abilities, organ and system functioning. 1 in 25,000 babies born will have some form of the mucopolysaccharidoses.

22. Symptoms  Intellectual disability Corneal clouding Developmental delay Retinal degradation Macroglossia (unusually enlarged tongue) Coarse facial features Hepatosplenomegaly (enlargement of both liver and spleen )

23. Function

24. Glycoconjugates

25. Glycoconjugates Classification family of   carbohydrates – referred to as  glycans . Covalentlylinked  with proteins, peptides,  lipid , and other compounds . Although the important molecular species   DNA ,  RNA ,  ATP , all contain a carbohydrate part, generally they are not considered as glycoconjugates . In 2021 glycoRNAs were observed for the first time .

26. Significance Glycoconjugates 1 2 3 4 Cell to cell recognition Cell to matrix interaction Detoxification Long term immunity response

27. Glycoconjugates There are various types: Glycoproteins Glycolipids Glycopeptides Glycosides Peptidoglycans Proteoglycans Types

28. Glycoproteins Glycoproteins are proteins containing glycans covalently attached to amino acid side chains. The carbohydrate may constitute from 1-70 % of mass. The  carbohydrate  is attached to the protein in a  posttranslational modification process known as  glycosylation . Within the cell, they appear in/on the: blood extracellular matrix 3. outer surface of the plasma membrane

29. Glycosylation  The carbohydrate constituent is attached to the protein via the -OH group of serine or threonine (i.e.  O -glycosylation) or the amide NH2 of asparagine (i.e.  N -glycosylation).

30. vg Examples Collagen Mucin s Secretions Immunoglobulins Lectin s Surface membrane glycoproteins Milk proteins Proteins secreted by pancreas

31. Glycoproteins and Corona virus COVID-19 has surface glycoproteins called spike domains; S (Latin ‘ crown-like’=‘corona ’), which enable it to bind to their target receptors. The S domain is the main site for antibodies to neutralize the viruses. Hence it is targeted for successful vaccination. The S domains (corona and influenza) are constantly changing (mutating), hence the seasonal epidemics, despite previous antibodies. COVID-19 has now mutated into many different variants. This has caused concern over the possibility of altering transmission or the effectiveness of vaccines .

32. Glycolipids A carbohydrate, usually an oligosaccharide, that is covalently linked to a  lipid  molecule. F ound on the extracellular face of eukaryotic cellular membranes. Can act as receptors for viruses and other pathogens to enter cells. The brain and neurons are rich in glycolipids.

33. Function Maintain stability of the membrane F acilitate cell–cell interactions Help in nerve conduction and myelin formation Play role in signal transduction

34. ABO Blood Group System Specific glycoproteins (and glycolipids) present on the surface of red blood cells determine blood group type. A-oligosaccharide for A group B -oligosaccharide for B group B oth A & B oligosaccharides for AB group, and A bsence of both A & B for O A fter ABO determination, P resence of Rh factor (an  antigen ) determines Rh +  groups W hereas the absence of the Rh antigen leads to Rh -  groups

35. Proteoglycans Proteoglycans  are  proteins  that are heavily  glycosylated. The GAGs extend perpendicular from the core protein in a bottlebrush- like structure. They act as polysaccharides rather than proteins as 95% of their weight is composed of GAG’s. Mammalian cells can produce 40 types of proteoglycans.

36. Structure The basic structure consists of a covalently linked Core protein with GAG/s The point of attachment is a serine residue. The GAGs extend perpendicular from the core protein in a bottlebrush- like structure. The GAG is joined to Ser via the tetrasaccharide bridge. The Ser residue is generally in the sequence -Ser- Gly -X- Gly .

37. 1. Core Protein  The basal lamina limits contact between epithelial cells and other groups. It contains a family of core proteins ( Mr 20000-40000 ). Each protein is with several covalently attached heparan sulphate. 2 major families of membrane heparan sulphate proteoglycans. Syndecans : have a single transmembrane domain and an extracellular domain The extracellular domain has 3-5 chains of HS and sometimes chondroitin sulphate. Glypicans: Only an extracellular domain Attached to membrane by a lipid anchor.

38. 2. GAG Chain  These can bind to extracellular ligands. Some domains (3-8 disaccharide units long) differ from neighbouring domains in sequence and binding ability. Highly sulphated domains (NS) alternate with domains having unmodified GlcNAc and GlcA residues. The exact pattern of sufation in NS domain depends om the particular proteoglycan.

39. Summary Heteropolysaccharides: contain two or more monosaccharide units e.g. GAGs, agar, peptidoglycans Glycosaminoglycans: Heteropolysaccharides of the ECM/ground substance. Structure: repeating two-sugar unit consists of a uronic sugar and an amino sugar Examples: hyaluronate, keratan sulphate, heparin, chondroitin suphate Mucopolysaccharidoses: group of  metabolic disorders  caused by the absence or malfunctioning of the 11 lysosomal   enzymes  needed to break down GAGs. Glycoconjugates: classification family for  carbohydrates. Types Glycoproteins: proteins containing glycans covalently attached to amino acid side chains. Glycolipids: A carbohydrate, usually an oligosaccharide, that is covalently linked to a  lipid  molecule. Proteoglycans: Proteoglycans  are  proteins  that are heavily  glycosylated. Significance

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