Expansion
Hydroxylation requires vitamin C, then glycosylation, triple helix formation and cross-linking
Expansion
- Synthesis of preprocollagen with the repeating glycine-X-Y sequence, where Y is often proline
- Hydroxylation of proline and lysine, requiring vitamin C as a cofactor
- Glycosylation of hydroxylysine
- Triple helix formation to give procollagen
- Exocytosis
- Cleavage of terminal propeptides to give tropocollagen
- Cross-linking by lysyl oxidase, which requires copper
Every third residue must be glycine, the smallest amino acid, because only it fits at the crowded centre of the triple helix. Substituting it is therefore severely disruptive.
Disorders map onto the steps:
- Scurvy: failed hydroxylation, giving unstable collagen. Bleeding gums, perifollicular haemorrhage, corkscrew hairs, poor wound healing
- Osteogenesis imperfecta: usually a glycine substitution in type I collagen. Blue sclerae, fractures, hearing loss
- Ehlers-Danlos: various defects in synthesis or processing, giving hypermobility and fragile skin and vessels
- Menkes disease: copper transport defect, so lysyl oxidase fails