Collagen

Question 1

Describe the structure of a basic collagen unit.

Answer 1

A triple helix composed of two a1 chains and an a2 chain.

Question 2

Describe collagen fiber formation (7 steps).

Answer 2

1. Prepro-alpha chains are transcribed and cotranslated into the ER.
2. ER signal sequence is cleaved, forming pro-alpha chains.
3. Select proline and lysine residues are hydroxylated, and hydroxylysine is then glycosylated.
4. Disulfide isomerase forms formation of the triple helix via interchain and intrachain disulfide bonds. It is now procollagen.
5. Procollagen is secreted from the cell, N and C terminal propeptides are cleaved by peptidases, forming tropocollagen.
6. Tropocollagen is hydrophobic, causing self assembly of fibrils.
7. Cross linking leads to formation of mature collagen fibers.

Question 3

Describe hydroxylsine formation.

Answer 3

Copper-dependent lysyl oxidase makes structure a reactive aldehyde, which down the road allows for spontaneous cross linking needed for mature collagen fiber assembly.

Question 4

What do lyssylhydroxylase and prolylhydoxylase require?

Answer 4

Cofactors oxygen and ascorbate.

Question 5

Describe scurvy.

Answer 5

Due to poor vitamin C intake.
Lysyl and prolyl hydroxylase are impaired, leading to structural issues in collagen triple helix. Their tensile strength decreases and they degrade moor easily.
Blood vessel and gum issues arise.

Question 6

Describe osteogenesis imperfecta regarding collagen.

Answer 6

Internal glycine residues of collagen triple helix are replaced with a bulky adduct, causing a bulge. Ability of bone to crystallize is compromised, leading to brittle bones.

Question 7

Describe ehlers danlos syndrome.

Answer 7

Phenotype is loose joints, stretchy skin, and abnormal scar formation. In severe cases blood vessel fragility results in fatal complications (sudden arterial rupture).
Note much of issue is due to dysfunction lysyl hydroxylase leading to lack of cross linking between mature collagen fibers.