2 - Overview of glycosaminoglycans 3rd Lecture: Pages :Glycosaminoglycans( Chapter 14 )- Overview of glycosaminoglycans- Structure of glycosaminoglycans :A. Relationship between glycosaminoglycansstructure and function
3 GlycosaminoglycansI - Definition:They are large complexes of negatively charged heteropolysaccharide (Mucopolysaccharides) chains containing modified forms of glucose.They are carbohydrates associated with small amount of protein forming proteoglycans (95% carbohydrates).Polymer of different monosaccharides
5 II - Importance: They have the ability to bind large amount of water to form the gel-like matrix that forms the basis of the body’s ground substances . So,1-They stabilize and support cellular and fibrous components of tissue2- They help in maintaining the water and salt balance of the body3- They play a role in mediating cell- cell interaction
6 4- Synovial fluid’s glycosaminoglycans serve as a lubricant in joint, tendon sheaths and bursae. 5- The character of connective tissue is dependent on the amount of ground substance (glycosaminoglycans) and embedded protein.e.g cartilage is rich in ground substance, whereas tendon is composed of fibers
8 III - Structure of glycosaminoglycans : They are long , unbranched formed from repeating disaccharides unit (Figures 14.1 & 14.2) :1-Amino sugar ; D-glucosamine or D-galactosamine in which the amino group is usually acetylated to eliminating its positive charge and they may be sulfated.2- Acidic sugar; D- glucuronic acid or its C5 epimar, “ L- iduronic acid” gives the glycosaminoglycans their strongly negative nature.
12 Relationship between glycosaminoglycans structure and function: 1- In water, due to their large number of negative charges, these heteropolysaccharide chains extended and surrounded with shell of water.2- When brought together, they “slip” past each other as 2 magnets “slippery” consistency of mucous secretion and Synovial fluid.
13 3- Squeezing water out of glycosaminoglycans decreasing their volumes . 4- On releasing the compression they return back to their original hydrated state.5-This property plays an important role in the resilience of Synovial fluid and vitreous humor of eye ( Figure 14.3).
18 B. Classification of glycosaminoglycans C. Structure of proteoglycans 4th Lecture: Pages : 155 – 157 & page 163 Glycosaminoglycans(Chapter 14)B. Classification of glycosaminoglycansC. Structure of proteoglycans
19 B.Classification of glycosaminoglycans (GAG): GAG are classified into 6 major classes according to :1- Monomeric composition2- Type of glycosidic linkages3- Degree and Location of sulphate units
20 The 6 major classes of Glycosaminoglycans are : (Figure 14.4) 1- Chondroitin 4- & 6- Sulfates2- Keratan Sulfates I & II3- Hyaluronic Acid.4- Dermatan Sulfate5- Heparin6- Heparan Sulfate
22 - The most heterogeneous GAG due to its 1- Chondroitin 4- & 6- Sulfates :- The most abundant GAG in the body.- Form proteoglycan aggregates together withhyaluronic acid.- Found in : cartilage, tendons, ligaments & aorta2- Keratan Sulfates I & II :- The most heterogeneous GAG due to itsmonosaccharides (L-fructose, mannose..etc) content.- Found in : - Loose connective tissue ( KS Type II )- Cornea ( KS Type I )
23 3- Hyaluronic Acid :- Differs from other GAG (unsulfated, not covalentlyattached to protein, the only GAG not limited toanimal tissue).- Serves as a lubricant and shock absorber- Found in : Synovial fluid of joints, vitreous humorof the eye, umbilical cord, loose CT & cartilages
25 - Found in : Skin, Blood vessels and Heart valves 5- Heparin : 4- Dermatan Sulfate :- Found in : Skin, Blood vessels and Heart valves5- Heparin :- Serves as an anticoagulant.- Found in : An intracellular component of mast cells liningthe arteries of Liver, Lungs and Skin.6- Heparan Sulfate :- Extracellular GAG.- Found in : - Basement membrane- As a ubiquitous component of cell surface
27 C. Structure of proteoglycans : 1-Structure of Proteoglycan monomers:- Proteoglycan monomer in the cartilage consists of a coreprotein to which the linear glycosaminoglycan chains arecovalently attached.- Each GAG chain composed of more than 100monosaccharides extend out from the core protein bottle brush. (Figure 14.5)- Cartilage Proteoglycan :GAG species include Chondroitin sulfate and keratansulfate .
30 3- Proteoglycan aggregates: are formed of Examples of Proteoglycans:- Syndecan : an integral membrane proteoglycan.- Versican & Aggregan :the most abundant extracellular proteoglycan- Neurocan & Cerebrocan : found in the nervous system2- Linkage between the carbohydrate chain and the protein :- Most commonly through trihexoside (galactose-galactose-xylose) & a serine residue.- An O - glycosidic bond between xylose and OH- groupof serine . (Figure 14.6)3- Proteoglycan aggregates: are formed ofproteoglycan monomers associated with hyaluronic acidwhich interacts ionically with the core protein, which isstabilized with small link proteins. (Figure 14.7)
35 Overview of Glycoproteins Glycoproteins are proteins to whicholigosaccharides are covalently attached.They differ from proteoglycans in that the length ofthe glycoprotein’s carbohydrate chain is relativelyshort (2-10 sugar residues).It can be very long in the glycosaminoglycans.
36 Overview of Glycoproteins …. contd The glycoprotein carbohydrate chains are often branched instead of linear and do not have serial repeats unlike that in glycosaminoglycans and may or may not be negatively charged.Glycoproteins contain highly variable amounts of carbohydrate:- IgG contains < 4% of its mass as CHO- human gastric glycoprotein (mucin) contains > 80%CHO.
37 Overview of Glycoproteins …. contd Membrane-bound glycoproteins participate widely in the cellular phenomena:- Cell surface recognition (by hormones, viruses &other cells).- Cell surface antigenicity ( Blood group antigens)- Components of extracellular matrix- Protective biological lubricants (Mucins of GIT &UGT ) ( Figure 14.13)Almost all the globular proteins present in human plasma are glycoproteins.