Biosynthesis of collagen

Question 1

What are the components of ECM?

Answer 1

Water
Proteins (collagen, elastin)
GAGs
Proteoglycans
Glycoproteins

Question 2

list the functions of ECM

Answer 2

Mechanical basis for cell attachment and movement
Transmits force
Reservoir for growth factors
Send survival signals to cells and differentiation signals to stem cells
Can withstand compression
Acts as a scaffold for tissue development

Question 3

What is a glycoprotein ?

Answer 3

Protein with carbohydrate side chains

Question 4

Through what process are sugar side chains added to glycoproteins and what enzyme is involved?

Answer 4

Glycosylation

Glycosyltransferase

Question 5

what is a proteoglycan, what is the ration of its protein to sugar content and what function does it have?

Answer 5

Proteoglycan: core protein with GAG chains covalently bound.
Protein is a minor component and carbohydrates are a major component.

Proteoglycans attract water and protect against compressive forces.

Question 6

Describe the structure of collagen

Answer 6

Consists of 3 alpha polypeptide chains which fold to form a triple helix structure. Each chain has a repeating triplet of amino acids: Gly-X-Y

Question 7

Explain the formation of fibrillar collagen in the cell

Answer 7

Pre-procollagen is made and signal peptidases are cleaved off in the rough ER. Chains are now called pro-alpha chains.

Hydroxylation of lysine and proline amino acids occurs. Vitamin C is a cofactor this process.

Further glycolsylation selected hydroxyl groups on lysine occurs.

Pro-alpha chains are assembled into a triple helical structure to form pro-collagen.

These are sent to Golgi apparatus for final modifications and assembly intro secretory vesicles.

Extracellular:
N and C peptidases cleave off pro peptides to form tropocollagen.

Tropocollagen molecules assemble to form collagen fibrils. Collagen fibrils aggregate to form collagen fibre.

Question 8

What does procollagen consists of?

Answer 8

Two alpha-1 chains

One alpha 2 chains

Question 9

what cross links collagen to make it stable?

Answer 9

Lysol oxidase

Question 10

NAme a disease caused by collagen mutations? and describe the mutation

Answer 10

Osteogenesis imperfecta (Brittle bone disease)

Type 1 collagen defect due to mutation in either COL1A1 or COL1A2 gene.

Question 11

What genes encode for alpha 1 and alpha 2 chains in type 1 collagen?

Answer 11

Alpha 1 - COL1A1

Alpha 2 - COL1A2

Question 12

What does the HSP47 protein code for? What is its role?

Answer 12

Codes for the triple helix of collagen molecule and prevents the aggregation of collagen molecules in the cell.

It is involved in packaging collagen molecules into secretary vesicles.

Question 13

what happens if the HSP47 protein does not function as required (mutates)?

Answer 13

Collagen monomers aggregate in the cells and are not packaged into vesicles = reduction in collagen

Question 14

What disease can mutation of HSP47 protein cause?

Answer 14

Osteogeneis imperfecta

Question 15

List 3 mutations that can cause OI

Answer 15

Promoter mutations - mRNA production is affected
Premature stop codon - protein not made
mRNA instability - reduced collagen formation

Question 16

What’s epidermolysis bullosa?

Answer 16

Mutation in collagen which detaches the basement membrane and creates blisters.

Question 17

Describe the mechanism of alport syndrome,

Answer 17

Mutations in type four collagen affect the glomerular basement membrane. The glomerular filtration apparatus breaks down and there’s blood in urine and thickening of fenestrations of glomerulus.