3/18/24, 3:31 PM
Proteoglycans
Extracellular matrix
Major component of connective tissue. Composed of:
- Fibres: collagen (strength) and elastin (elasticity)
- Proteoglycans form ‘ground substance’ (hydrated gel)
- Adhesive glycoproteins: Fn Ln
Proteoglycan
➢ Proteo- have a protein component (protein core)
➢ Glycan- contains glycosaminoglycans covalently attached to the protein core
Thus, they have a core protein, GAG chains (long, unbranched and approx. 80 sugars long). They can
be up to 95% carb and they vary in size (Aggrecan is very large, over 100 GAG chains whereas
Decorin is only one GAG chain long)
Function:
o Binds water hydrated matrices
o Fill space between cells
o Absorb compressive forces
o Interact with collagens
o Bind and store growth factors
Proteoglycan protein cores
=complex proteins with multifunctional domains. These are involved in protein-protein, protein-carb
and protein-cell interactions that help to hold the tissue/its components together.
Glycosaminoglycans (GAG)
These GAGs are covalently linked to the protein core through the hydroxyl groups of serine or
threonine residues or the amine group of asparagine of these amino acids
Composition of GAGs:
They are attached to the protein core. Up to 95% carbs come in the form of GAGs. 6 main classes:
- Hyaluronan
- Chondroitin sulphate
- Dermatan sulphate
- Keratan sulphate
- Heparan sulphate
- Heparin
Structure:
(GAG repeating disaccharide)
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, 3/18/24, 3:31 PM
Properties:
• Chains do not fold. (extended conformation. Occupy large volume in comparison to mass)
• Negative charge attracts cations .e.g. Na+/K+
• Osmotically active tissue
• Highly hydrophilic (draws water into matrix, creates pressure that resists compressive
forces)
• Acts as a gel
Distribution of main GAGs
Keratin and chondroitin sulphate=most
common
Hyaluronan is different- not bound to
core protein and no sulphation
Proteoglycan synthesis
Core protein formed +GAG in golgi +link trisaccharide to either serine for
heparan/ chondroitin sulphate or to asparagine for keratan sulphate Transfer
glycosyl unit from nucleotide derivative to adjacent sugar
This requires specific enzymes such as Glycosyl transferases
Hyaluronan (hyaluronic acid, hyaluronate)
➢ Up to 25,000 disaccharide units
➢ Very long chain which is flexible, bend & twist
➢ Synthesised on cell surface by enzyme complex in plasma membrane
➢ No core protein, no sulphation
➢ Interacts with other ECM components
Function:
▪ Forms backbone of complexes with aggregating PGs
▪ Large number anionic residues-binds much water
▪ Osmotic pressure by cation binding
▪ Development-surrounds migrating and proliferating cells
▪ Wound healing
▪ Lubricant-for joints in synovial fluid 0.3% hyaluronic acid and hyaluronate-based gel (e.g.
vitreous humour-eye and Wharton’s jelly-umbilical cord).
Heparin and heparan sulphate
• Repeat unit glucosamine & D-glucuronic acid (or L-iduronic acid)
• Usually sulphated
Heparin- Hypersulphated form, released in allergic reactions (preventing excessive fibrin formation in the interstitium), only
synthesised by mast cells
Heparan sulphate=all cells.
Functions: Anticoagulant-prevents activation of clotting factors by binding to an inhibitor of coagulation, Lipid clearing
agent, Binds fibroblast growth factor.
2/5
Proteoglycans
Extracellular matrix
Major component of connective tissue. Composed of:
- Fibres: collagen (strength) and elastin (elasticity)
- Proteoglycans form ‘ground substance’ (hydrated gel)
- Adhesive glycoproteins: Fn Ln
Proteoglycan
➢ Proteo- have a protein component (protein core)
➢ Glycan- contains glycosaminoglycans covalently attached to the protein core
Thus, they have a core protein, GAG chains (long, unbranched and approx. 80 sugars long). They can
be up to 95% carb and they vary in size (Aggrecan is very large, over 100 GAG chains whereas
Decorin is only one GAG chain long)
Function:
o Binds water hydrated matrices
o Fill space between cells
o Absorb compressive forces
o Interact with collagens
o Bind and store growth factors
Proteoglycan protein cores
=complex proteins with multifunctional domains. These are involved in protein-protein, protein-carb
and protein-cell interactions that help to hold the tissue/its components together.
Glycosaminoglycans (GAG)
These GAGs are covalently linked to the protein core through the hydroxyl groups of serine or
threonine residues or the amine group of asparagine of these amino acids
Composition of GAGs:
They are attached to the protein core. Up to 95% carbs come in the form of GAGs. 6 main classes:
- Hyaluronan
- Chondroitin sulphate
- Dermatan sulphate
- Keratan sulphate
- Heparan sulphate
- Heparin
Structure:
(GAG repeating disaccharide)
1/5
, 3/18/24, 3:31 PM
Properties:
• Chains do not fold. (extended conformation. Occupy large volume in comparison to mass)
• Negative charge attracts cations .e.g. Na+/K+
• Osmotically active tissue
• Highly hydrophilic (draws water into matrix, creates pressure that resists compressive
forces)
• Acts as a gel
Distribution of main GAGs
Keratin and chondroitin sulphate=most
common
Hyaluronan is different- not bound to
core protein and no sulphation
Proteoglycan synthesis
Core protein formed +GAG in golgi +link trisaccharide to either serine for
heparan/ chondroitin sulphate or to asparagine for keratan sulphate Transfer
glycosyl unit from nucleotide derivative to adjacent sugar
This requires specific enzymes such as Glycosyl transferases
Hyaluronan (hyaluronic acid, hyaluronate)
➢ Up to 25,000 disaccharide units
➢ Very long chain which is flexible, bend & twist
➢ Synthesised on cell surface by enzyme complex in plasma membrane
➢ No core protein, no sulphation
➢ Interacts with other ECM components
Function:
▪ Forms backbone of complexes with aggregating PGs
▪ Large number anionic residues-binds much water
▪ Osmotic pressure by cation binding
▪ Development-surrounds migrating and proliferating cells
▪ Wound healing
▪ Lubricant-for joints in synovial fluid 0.3% hyaluronic acid and hyaluronate-based gel (e.g.
vitreous humour-eye and Wharton’s jelly-umbilical cord).
Heparin and heparan sulphate
• Repeat unit glucosamine & D-glucuronic acid (or L-iduronic acid)
• Usually sulphated
Heparin- Hypersulphated form, released in allergic reactions (preventing excessive fibrin formation in the interstitium), only
synthesised by mast cells
Heparan sulphate=all cells.
Functions: Anticoagulant-prevents activation of clotting factors by binding to an inhibitor of coagulation, Lipid clearing
agent, Binds fibroblast growth factor.
2/5
