Sheet #7 Lecture (Glycoproteins Lecture Part 1 ) Lecture Date :- 11-7-2018

1. Sheet #7 Lecture (Glycoproteins Lecture Part 1) Lecture Date :- 11-7-2018 Done & Edited By :- سندس نصار & Tasneem Al-Abbadi

2. If you come by any mistake (whether it be spelling, grammatical or scientific) while browsing this sheet, kindly report it to the academic team 2023od@gmail.com

3. Complex CarbohydratesGlycosaminoglycans(GAGs) Glycoproteins and proteoglycans

4. LECTURE OUTLINE • Differences between glycoproteins and proteoglycans • Structures of glycoproteins and proteoglycans • Functions of glycoproteins and proteoglycans • Synthesis and degradation of glycoproteins and proteoglycans • Pathology related to glycoproteins and proteoglycans

5. Differences Between Glycoproteins and Proteoglycans Proteins conjugated to saccharides lacking a serial repeat unit Glycoproteins Protein>>carbohydrate Proteins conjugated to polysaccharides with serial repeat units Glycosaminoglycans Mucopolysaccharides Carbohydrate>>protein Proteoglycans البروتينات اكثر من الكربوهيدرات ولا تحتوي على Glycoprotein نفس العيله لكن ال Serial repeat unit الكربوهيدرات اكثر من البروتينات وتحتوي على Proteoglycan بينما بال Serial repeat unit

6. Glycoprotein ) ## addition of carbohydrates to protein ) ## Oligo means less than 10 units *few* ## Poly means a lot ,more than 100 *عديد* Glycoproteins are proteins that contain oligosaccharide chains (glycans) covalently attached to their polypeptide side-chains. The process of attaching the glycans is known as glycosalation. The sugar groups attached to glycoprotein can assist in protein folding or improve a proteins’ stability.

7. Sheet 1 • Glycosalation : amino acid will be addition to it during modification • Hydroxyl protein is an modifying amino acid then it passes through hydroxylation by vitamin C • We have a lot of factors that effect the protein folding like ; sugar groups ,bonds , interactions

8. The disaccharide units contain either of two modified sugars, called amino sugarsN-acetylgalactosamine (GalNAc) or N-acetylglucosamine (GlcNAc), • and an acidic sugar uronic acid such as glucuronic acid or iduronic acid. • The amino group is usually acetylated.

9. In some glycosaminoglycans, one or more of the hydroxyls of the amino sugar is esterified with sulfate. • The combination of these sulfate groups and the carboxylate groups of the uronic acid residues gives the glycosaminoglycans a very high density of negative charge. • Keratan sulfate is an exception in which galactose is present, instead of an acidic sugar. • Hyaluronic acid does not contain sulfate.

10. Sheet 2 We have hydroxyl amino acid and sulfate amino acid .. And we have a carbohydrate group which attached to amino acid and urinic acid to give negative charge

11. Structure of Glycosaminoglycans • GAGs in the body are linked to core proteins ( except hyaluronic acid), forming proteoglycans (also called mucopolysaccharides). • The GAGs extend perpendicularly from the core in a brush-like structure. • e.g. in cartilage proteoglycan the GAGs present are chondriotin sulfate and keratan sulfate

13. Proteoglycan Aggregates • Proteoglycan monomers associate with a molecule of hylauronic acid to form proteoglycan aggregates in association with linker proteins in a “bottle brush” arrangement.Association is not covalent but ionic between hyaluronic acid and the core protein. • Stabilized by link proteins

14. Proteoglycan aggregate of the extracellular matrix ##The backbone ##Modified sugars One very long molecule of hyaluronan is associated noncovalently with about 100 molecules of the core protein aggrecan

15. Interactions between cells and the extracellular matrix with binding sites for both integrin and the proteoglycan

16. Linkage • The linkage of GAGs to the protein core involves a specific trisaccharide composed of two galactose residues and a xylose residue (Gal-Gal-Xyl-O-CH2-protein).

18. The trisaccharide linker is coupled to the protein core through an O-glycosidic bond to a Serine residue in the protein. • Some forms of keratan sulfates are linked to the protein core through an N-glycosidic bond. • The protein cores of proteoglycans are rich in Serine and Threonine residues, which allows multiple GAG attachments. ##(both of them have hydroxyl amino acid )

19. STRUCTURE OF GLYCOPROTEINS One or more carbohydrate chains--covalently linked to a protein. The chains may be neutral or negatively charged. They are frequently branched. There are two types of glycosidic links: 1. O-glycosidic link O-glycosidic link between galactose or glucose and the hydroxyl group of hydroxylysine (i.e. collagen). Other O-linked glycoproteins have a glycosidic link between N-acetyl galactosamine and either serine or threonine (i.e. blood group substances and salivary mucins). 2. N-glycosidic link N-glycosidic links exist between N-acetylglucosamine and asparagine. There are two types: A. High mannose B. Complex. For example, in addition to mannose they may contain N-acetylglucosamine, galactose, fucose and N-acetylneuraminic acid (sialic acid)

20. Lippincott

21. Their core pentasaccharide is the same. In the complex form additional sugar residues are present: N-acetylglucosamine (GlcNAc) and N-acetylneuraminic acid (NANA). Fucose

22. Eight Sugars in Glycoproteins

23. Glycoproteins Glycoproteins are proteins that contain oligosaccharide (glycan) chains covalently attached to their polypeptide backbones. Glycoproteins occur in most organisms, from bacteria to humans. Their carbohydrate content ranges from 1% to over 85% by weight.

24. They differ from proteoglycans: Length of the chain is relatively short (usually 2-10 sugar residues) very long in GAGs. Do not have repeating disaccharide units. They are branched. May or may not be negatively charged.

25. The distinction between proteoglycans and glycoproteins resides in the level and types of carbohydrate modification.

26. Proteoglycans also contain the sugar glucuronic acid (GlcA). The carbohydrate modifications found in glycoproteins are rarely as complex as that of proteoglycans. Most proteins that are secreted, or bound to the plasma membrane, are modified by carbohydrate attachment. The part that is modified, in plasma membrane-bound proteins, is the extracellular portion of the protein.

27. Intracellular proteins are less frequently modified by carbohydrate attachment. However, the attachment of carbohydrate to intracellular proteins confers unique functional activities on these proteins

28. Structure of Glycoprotein The oligosaccharide components of glycoproteins  is branched heteropolymers  composed of D-hexoses, with the addition in some cases of neuraminic acid, and of L-fucose (6-deoxyhexose)

29. FUNCTIONS

30. Some Functions of Glycoproteins _________________________________________________ Function Glycoprotein _________________________________________________ 1. Structural molecule Collagens/Arthritis Proteins& modified sugars 2. Lubricant Mucins/ Peptic ulcer For protection 3. Transport molecule e.g. Transferrin, For iron Ceruloplasmin For copper 4. Immune system Immunoglobulins, Histocompatibility antigens, Blood group determinants 5. Hormone e.g. HCG, TSH ( + NH, NSH) fertilization مسؤول عن ال HCGهرمون ال chains و بختلفو بالبيتا Polypeptide chain الهرمونات بتشابهو بال 6. Enzymes e.g. Alkaline phosphatase 7. Blood clotting e.g. Fibrinogen 8. Blood groups 9. Cell surface recognition Lectins

31. Glycoproteins • Glycoproteins contain carbohydrate units covalently bonded to a polypeptide chain • antibodies are glycoproteins • carbohydrates play a role as antigenic determinants, the portions of the antigenic molecule that antibodies recognize and to which they bond.

32. Almost all the plasma proteins of humans—except albumin—are glycoproteins. For example, O-linked oligosaccharides on the surface of RBCs help provide the ABO blood group determinants Many proteins of cellular membranes contain substantial amounts of carbohydrate.

33. Blood Group Substances • Membranes of animal plasma cells have large numbers of relatively small carbohydrates bound to them: • these membrane-bound carbohydrates act as antigenic determinants • among the first antigenic determinants discovered were the blood group substances • in the ABO system, individuals are classified according to four blood types: A, B, AB, and O • at the cellular level, the biochemical basis for this classification is a group of relatively small membrane-bound carbohydrates

34. ABO Blood Classification ( يستقبل من الكل)Gal & GalNAcيحتوي ال *AB*ال

35. ABO Blood Classification • in type A, the nonreducing end is NAGal • in type B it is Gal • in type AB, both types are present • in Type O, neither of these terminal residues is present

36. Recognition and adhesion at the cell surface ( وتتحد معهاtoxin, viruses ,,وتتعرف على اي من الrecognition site (الهدف من الجلايكوبروتين انها تكون

40. lectin-ligand interactions in lymphocyte movement to the site of an infection Stronger interaction near the site of inflammation

41. Helicobacter pylori Interaction between a bacterial surface lectin and an oligosaccharide of the gastric epithelium

42. Sheet 3 • Helicobacter : bacterial surface • It’s cause ulcers of stomach • Acid media in stomach = 2.5 • It has been shown to be treated by antibiotics rather than by antiacidic • It may be convert to cancer

43. معلومة من خارج كلام الدكتور H. pylori is a common type of bacteria that grows in the digestive tract  and has a tendency to attack the stomach lining. It infects the stomachs of roughly 60 % of the world’s adult population. H. pylori infections are usually harmless, but they’re responsible for the majority of ulcers in the stomach and small intestine.

44. The extracellular space in animal tissues is filled with a gel-like material, the extracellular matrix, also called ground substance, • which holds the cells of a tissue together and provides a porous pathway for the diffusion of nutrients and oxygen to individual cells.

45. Epithelial cells extra-cellularmatrix Underlying cells

46. Sheet 4 • Extracellular matrix = ground substance • It’s contain glycoproteins • It’s passage pathway for nucleus component

47. The extracellular matrix is composed of an interlocking meshwork of heteropolysaccharides and fibrous proteins. • Heteropolysaccharides in the body are the glycosaminoglycans (GAGs). These molecules are long unbranched polysaccharides containing a repeating disaccharide unit.

48. GAGs are highly negatively charged molecules, with extended conformation that imparts high viscosity to the solution. Important function • GAGs are located primarily on the surface of cells or in the extracellular matrix (ECM).

49. Along with the high viscosity of GAGs comes low compressibility, which makes these molecules ideal for a lubricating fluid in the joints. • Work as shock absorption • At the same time, their rigidity provides structural integrity to cells and provides passageways between cells, allowing for cell migration.

50. Hyaluronic acid • Hyaluronic acid is unique among the GAGs in that it does not contain any sulfate and is not found covalently attached to proteins as a proteoglycan. • It is, however, a component of non-covalently formed complexes with proteoglycans in the ECM.