Synthesis Of Collagen & Insulin

Question 1

What is the main role of collagen in the body?

Answer 1

• Most abundant protein in the body (25-35%)
• Most abundant fibrous protein in connective tissue
• Provides structure and support of tissues and organs
• Tendons, ligaments, cartilage, bone

Question 2

What type of cells produce and secrete collagen?

Answer 2

Fibroblasts (in connective tissue)

Question 3

Describe the structure of collagen fibres

Answer 3

• Basic unit is TROPOCOLLAGEN
• 300nm rod shaped protein
• 3 polypeptide α chains twisted into a right handed triple helix
• GLY - X - Y repeating structure
• Each polypeptide chain is ~1000 AA long

Question 4

What are the structural advantages of the triple helix structure of collagen?

Answer 4

• Non extensible
• Non compressible
• High tensile strength

Question 5

What bonds are present within the 3 polypeptide chains?

Answer 5

H bonds between α chains

Question 6

Which amino acids are most abundant in collagen?

Answer 6

• Glycine
• Proline/Hydroxyproline
• Arginine
• Lysine

Question 7

List 2 things needed for the activation of PROLYL HYDROXYLASE

Answer 7

• Vitamin C

- Fe2+ ions

Question 8

Explain why a lack of vitamin C can cause scurvy

Answer 8

• Vitamin C needed for the activation of prolyl hydroxylase
• Inhibition of prolyl hydroxylase means less hydroxylation of Pro residues on procollagen
• Less OH groups means less H bonds between tropocollagen fibrils so weakened tropocollagen triple helices
• Connective tissue defects

Question 9

Why is tropocollagen cleaved outside of the cell?

Answer 9

Covalent cross linking of tropocollagen would occur inside cell and destroy it

Question 10

What is needed for the activation of lysyl oxidase?

Answer 10

• Vitamin B6

- Cu2+ ions

Question 11

Explain how cross linking between tropocollagen molecules occurs

Answer 11

• Covalent cross links between Lysine residues using LYSYL OXIDASE
• Spontaneous bonding between aldehyde derivatives forming ALDOL CROSS LINKS

Question 12

Explain the type of bonding present in collagen molecules

Answer 12

• H bonding between α chains (3 together form tropocollagen)
• Covalent cross links between tropocollagen molecules forming collagen fibrils
• Aggregations of collagen fibrils form collagen fibres

Question 13

Explain why collagen has a striated appearance under a microscope

Answer 13

• Lateral association of tropocollagen molecules and cross linking forms OVERLAPPING
• Lighter staining regions with no overlap
• Darker staining regions where gaps are (dye fills the gaps)

Question 14

What can cause Ehlers-Danlos syndrome?

Answer 14

• Mutation in collagen type V

- Lysyl oxidase deficiency

Question 15

Explain how the cell prevents collagen cross linking inside the cell

Answer 15

Secretion of LYSYL OXIDASE out of cell which is required for the cross linking of tropocollagen molecules

Question 16

Describe the formation of procollagen in the RER

Answer 16

• Preprocollagen synthesised in ribosomes contains N terminal signal peptide
• SRP recognises signal peptide and directs preprocollagen towards RER cisternae
• Preprocollagen enters RER and signal peptide is CLEAVED by signal peptidase enzyme forming procollagen

Question 17

Explain the modifications that take place in the RER of procollagen

Answer 17

• Hydroxylation of PROLINE and LYSINE residues to form HYDROYPROLINE and HYDROXYLYSINE
• PROLYL HYDROXYLASE
• Addition of N linked oligosaccharides to Arg residues
• Addition of GALACTOSE to hydroxylysine residues

Question 18

Describe the formation of tropocollagen from procollagen secreted from the Golgi

Answer 18

• Modified procollagen secreted from Golgi into a transport vesicle
• Procollagen vesicle travels to plasma membrane and is exocytosed from cell
• N and C termini of procollagen are cleaved by SPECIFIC ENDOPEPTIDASES forming tropocollagen

Question 19

Where in the cell does the formation of the triple helix of procollagen occur?

Answer 19

RER

Question 20

Describe how the association of tropocollagen molecules leads to the formation of a collagen fibre

Answer 20

• Lateral association of tropocollagen molecules
• Overlapping (striated appearance)
• Covalent cross linking between Lys residues on adjacent tropocollagens catalysed by LYSYL OXIDASE
• Spontaneous ALDOL cross linking between aldehyde derivative groups forming collagen FIBRIL
• Aggregations of fibrils form FIBRES