Presentation on theme: "(Chapter 7). Glycosaminoglycans ( Chapter 14 ) - Overview of glycosaminoglycans - Structure of glycosaminoglycans : A. Relationship between glycosaminoglycans."— Presentation transcript:
Glycosaminoglycans ( Chapter 14 ) - Overview of glycosaminoglycans - Structure of glycosaminoglycans : A. Relationship between glycosaminoglycans structure and function 3 rd Lecture: Pages :
Glycosaminoglycans I - 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
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 tissue 2- They help in maintaining the water and salt balance of the body 3- They play a role in mediating cell- cell interaction
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
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.
A.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.
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).
Glycosaminoglycans (Chapter 14) B. Classification of glycosaminoglycans C. Structure of proteoglycans 4 th Lecture: Pages : 155 – 157 & page 163
B. Classification of glycosaminoglycans (GAG): GAG are classified into 6 major classes according to : 1- Monomeric composition 2- Type of glycosidic linkages 3- Degree and Location of sulphate units
The 6 major classes of Glycosaminoglycans are : (Figure 14.4) 1- Chondroitin 4- & 6- Sulfates 2- Keratan Sulfates I & II 3- Hyaluronic Acid. 4- Dermatan Sulfate 5- Heparin 6- Heparan Sulfate
1- Chondroitin 4- & 6- Sulfates : - The most abundant GAG in the body. - Form proteoglycan aggregates together with hyaluronic acid. - Found in : cartilage, tendons, ligaments & aorta 2- Keratan Sulfates I & II : - The most heterogeneous GAG due to its monosaccharides (L-fructose, mannose..etc) content. - Found in : - Loose connective tissue ( KS Type II ) - Cornea ( KS Type I )
3- Hyaluronic Acid : - Differs from other GAG (unsulfated, not covalently attached to protein, the only GAG not limited to animal tissue). - Serves as a lubricant and shock absorber - Found in : Synovial fluid of joints, vitreous humor of the eye, umbilical cord, loose CT & cartilages
4- Dermatan Sulfate : - Found in : Skin, Blood vessels and Heart valves 5- Heparin : - Serves as an anticoagulant. - Found in : An intracellular component of mast cells lining the arteries of Liver, Lungs and Skin. 6- Heparan Sulfate : - Extracellular GAG. - Found in : - Basement membrane - As a ubiquitous component of cell surface
C. Structure of proteoglycans : 1-Structure of Proteoglycan monomers: - Proteoglycan monomer in the cartilage consists of a core protein to which the linear glycosaminoglycan chains are covalently attached. - Each GAG chain composed of more than 100 monosaccharides extend out from the core protein bottle brush. (Figure 14.5) - Cartilage Proteoglycan : GAG species include Chondroitin sulfate and keratan sulfate.
Examples of Proteoglycans: - Syndecan : an integral membrane proteoglycan. - Versican & Aggregan : the most abundant extracellular proteoglycan - Neurocan & Cerebrocan : found in the nervous system 2- 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- group of serine. (Figure 14.6) 3- Proteoglycan aggregates: are formed of proteoglycan monomers associated with hyaluronic acid which interacts ionically with the core protein, which is stabilized with small link proteins. (Figure 14.7)
Overview of Glycoproteins Glycoproteins are proteins to which oligosaccharides are covalently attached. They differ from proteoglycans in that the length of the glycoprotein ’ s carbohydrate chain is relatively short (2-10 sugar residues). It can be very long in the glycosaminoglycans.
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. 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. Overview of Glycoproteins …. contd