Fibrous EC matrix proteins: tendons etc

Question 1

Give 3 examples of pathological conditions associated with EC matrix abnormalities:

Answer 1

• Arthritis
• Osteoperosis
• Cancer
• Diabetes
• Ageing
• Various genetic diseases
• Scars/fibrosis

Question 2

What makes up the EC matrix?

Answer 2

• Ground substance components such as glycoproteins and proteoglycans.
• Fibrous proteins such as collagen and elastin

Question 3

What is the organisation of collagen in tendons, bone and cartilage?

Answer 3

Cartilage = meshwork
Bone = spirals
Tendons/ligaments = parallel bundles

Question 4

What is the structure of collagen?

Answer 4

• Triple helix of alpha chains
• Alpha chains are typically 3 AA repeats
• GLY-X-Y
• X is usually proline and Y is usually hydroxyproline
• Triple helices cross-link to form a fibril

Question 5

What is the process of synthesis of fibril-forming collagens

Answer 5

• Pro-alpha chains (modified in ER, triple helix formed)
• Procollagen(secreted, propeptides cleaved)
• Collagen
• assembly into collagen fibrils (striated appearance)
• Formation of covalent cross-links (strength)

Question 6

What are the two types of collagens?

Answer 6

Fibrillar collagens (e.g. I, III)
Sheet-like collagens (e.g. IV)

Question 7

Collagen IV vs Fibrillar collagens

Answer 7

• lack regular glycine = loose helix (increased flexibility, sensitivity to digestion with proteases)
• terminal peptides are not cleaved
• assemble “head to head” - form a sheet

Question 8

What are elastic fibres made of?

Answer 8

Elastin core covered by a sheath of microfibrils

• Microfibrils composed of glycoproteins such as fibrillin
• elastin is cross-linked to form elastic fibres

Question 9

What happens to elastin in hypertension?

Answer 9

• 50% of the large vessel walls is elastin
• In hypertension, there is increased synthesis and deposition of elastin and collagen in vessel walls
• thicker walls with a reduced diameter

Question 10

What happens to elastin in emphysema?

Answer 10

There is increased degradation of elastin

- loss of elastin = reduced elasticity of the lungs

Question 11

Why could there be a loss of elastin?

Answer 11

• emphysema

- deficiency of a1-anti-trypsin (normally inhibits elastase - too much elastase = excessive degradation)