(Chapter 7)

Glycosaminoglycans

( Chapter 14 )

- Overview of glycosaminoglycans

- Structure of glycosaminoglycans : A. Relationship between glycosaminoglycans structure and function

3rd Lecture: Pages : 155-156

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).

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        Glycosaminoglycans (Chapter 14)

B. Classification of glycosaminoglycans C. Structure of proteoglycans  

4th 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

2

3

4

5

6

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)

O-glycosidic bond

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

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