linkages in Proteoglycan Functions of Proteoglycan

1. Clinical Biochemistry
Dr. Ali Raza
Senior Lecturer
Centre for Human Genetics and Molecular Medicine (CHGMM),
Sindh Institute of Medical Sciences (SIMS), SIUT.

2. PROTEOGLYCANS
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3. • Carbohydrate content varies in combination with proteins.
• Carbohydrate is > 4 per cent, called Mucoproteins
• Carbohydrate is < 4 per cent, called Glycoproteins
• The amount of carbohydrates is ~ 95%, Proteoglycan
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4. PROTEOGLYCANS
• Proteins are covalently linked to glycosaminoglycans (GAGs)
• Proteoglycans are conjugated proteins.
• Any of the GAGs can take part in its formation.
Hyaluronic acid (HA);
keratan sulphates I and II,
Chondroitin Sulphates A, B, C,
Heparin
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5. Proteoglycan (Linkages)
Three types of linkages between GAG and protein is observed.
• O-glycosidic linkage: between N-acetyl galactosamine and serine or
threonine of the protein.
Example: keratan SO4 II
• O-glycosidic linkage: Formed between xylose and serine of the
protein.
This bond is unique to proteoglycans.
• N-glycosylamine linkage: Formed between N-acetyl glucosamine
and amide N of asparagine (ASn) of core protein.
Example: keratan SO4I and N-linked glycoproteins.
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6. Functions of Proteoglycans
1- As a constituent of extracellular matrix :
Interacts with collagen and elastin
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7. 2- Acts as Polyanions
• GAGS present in proteoglycans are Polyanions
(Negatively charged sulfate)
• Bind to Polycations (Na/ K/ Ca).
• Attracts water by osmotic pressure
into extracellular matrix contributing
to its turgor.
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8. 3- Acts as a barrier in tissue:
• Hyaluronic acid acts Cementing substance
and contributes to tissue barrier
• Permit metabolites to pass through
• Resist penetration bacteria and other infective agents.
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9. 4- Role in Release of hormone:
• Endogenous heparin is stored in
secretory granules of mast cells.
• Hyaluronic acid are present in storage or secretory
granules,
• where they play part in release of the contents of the
granules.
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10. 5- Role in cell migration in embryonic tissues:
• Hyaluronic acid is present in high conc. in embryonic
tissues
• Role in cell migration during Morphogenesis
and Wound repair.
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11. 6- Role in Glomerular filtration:
• Hyaluronic acid is present in basement membrane (BM) of
glomerulus of kidney
• where it plays important role in charge selectiveness of glomerular
filtration.
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12. 7- Role as anticoagulant
• heparin is an important anticoagulant
• It binds with factor IX and XI, plasma antithrombin III
• fibrinogen is not converted to fibrin.
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13. 8- Acts as lubricant in joints
• Hyaluronic acid in joints acts as a
• lubricant and shock absorbant.
• Injection of hyaluronic acid in knee joints is used to reduce
pain in chronic osteoarthritis of knee joints.
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14. 9- Role as a coenzyme:
• Heparin increases the activity of Lipoprotein lipase.
• Heparin binds to the enzyme present in capillary walls,
releasing of the Lipoprotein lipase into the circulation.
• Heparin is called as Clearing factor.
HSPG: Heparin sulfate Proteoglycan; LPL: Lipoprotein Lipase
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15. 10- As a Receptor of cell
• Proteoglycans like heparan sulphate are components of plasma
membrane of cells
• They act as receptors and participate in cell adhesion and cell-cell
interactions.
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16. 11- Role in compressibility of cartilages:
• Chondroitin sulphates and hyaluronic acid are present in
high concentration in cartilages
• Role in compressibility of cartilage in weight bearing.
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17. 12- Role in sclera of eye:
• Dermatan sulphate is present in sclera of the eye
• Maintaining overall shape of the eye.
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Reference:
Textbook Medical Biochemistry by Chatterjea,
Eight Edition, Chapter 3
https://www.amazon.com/Textbook-Medical-Biochemistry-M-D-
Chatterjea/dp/9350254840