OI results from impairement of:
Alpha triple helix formation during collagen synthesis
Mainly I, some III
What cofactor is required for hydroxylation of proline and lysine during collagen synthesis?
In what form is collagen exocytosed into ECM during synthesis?
Procollagen (already in triple helix)
Most common type of Ehlers-Danlos?
Hypermobile type (joint instability)
Where is the alpha chain triple helix of precollagen formed?
RER of fibroblast
Consensus sequence of collage
Best reflection of collagen synthesis?
Glycine uptake by fibroblasts
Where is type IV collagen found?
Basement membrane, basal lamina, lens
What causes Menke disease?
Lack of copper transport and absorption --> no copper for lysyl oxidase cross-linking of lysine-hydroxylysine
Where is type I collagen found?
Bone, skin, tendon, fascia, dentin, cornea, late wound repair
Kinky hair + growth retardation + hypotonia
Which preprocollagen residues are hydroxylated in the RER of fibroblasts?
Proline and lysine
Where is type III collagen found?
Blood vessels, granulation tissue, fetal tissue, uterus, skin
Hyperextensible skin + easy bruising/tendency to bleed + hypermobile joints
Multiple fractures + hearing loss + dental imperfections
Where is type II collagen found?
Cartilage (including hyaline), nucleus pulposus, vitreous body
Is type I collagen defective in OI?
No, just reduced production of otherwise normal type I collagen
Which residue of preprocollagen gets glycosylated in the RER of fibroblasts?
Scurvy results in failure of which step of collagen synthesis?
Hydroxylation of proline and lysine in RER of fibroblast
Which type of collagen is underproduced in osteogensis imperfecta?
Name 5 diseases associated with collagen.
1. OI (no type I)
2. Ehlers-Danlos (no cross-linking)
3. Alport (defective IV)
4. Goodpasture's (autoantibodies against IV)
5. Menkes disease (no copper for lysyl oxidase)
Late wound repair
Risk of joint dislocation, aortic or berry aneurysms, organ rupture
Most common type of collagen
Which steps in collagen synthesis occur outside the fibroblast?
Cleave of terminal disulfide-bonds of procollagen to form tropocollagen
Cross-linking of lysine-hydroxylysine
Which enzyme cross-links collagen? What is its co-factor?
Mode of inheritance: OI