Step One Review: Collagen

Introduction to Collagen

Type I
- Composes 90% of bone; most common type.
- Found in skin, tendon, dentin, fascia, and cornea.
- Produced by osteoblasts.
- Osteogenesis imperfecta: decreased production of Type I collagen.
Type II
- Composes cartilage, including hyaline cartilage.
- Found in the vitreous body of the eye and nucleus pulposus.
- Nucleus pulposus: jelly-like substance in vertebrae; withstands compression and torsion.
Type III
- Composes reticular fibers in skin, blood vessels, uterus, and fetal tissue.
- Associated with Ehlers-Danlos syndrome (deficiency in Type III collagen).
Type IV
- Composes the basement membrane, specifically the basal lamina.
- Layer of ECM secreted by epithelial cells.
- Associated Conditions:
  - Alport syndrome: defective Type IV collagen.
  - Goodpasture syndrome: autoantibodies target Type IV collagen.

Peptide Sequence: Glycine-X-Y (X and Y are usually proline or lysine).
Produced in the rough endoplasmic reticulum (ER).
Hydroxylation:
- Proline and lysine residues are hydroxylated (requires Vitamin C).
- Lack of Vitamin C leads to scurvy.
Hydroxyproline assay: useful for collagen quantification (specific to collagen).

Individual chains called pro-alpha chains are glycosylated at hydroxyl lysine residues.
Three alpha chains come together via hydrogen bonds and disulfide bridges to form a triple helix.
Failure to form a triple helix leads to osteogenesis imperfecta.
Triple helix is exocytosed as procollagen into the ECM.
Cleavage: Enzymes cleave ends rich in disulfide bonds, creating insoluble collagen fibers (triple collagen).
Cross-linking:
- Enzymes (lysol oxidases) link lysine to hydroxyl lysines, forming final collagen fibrils.
- Failure to cross-link results in Menke's disease.