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Collagen has a Glycine-X-Y primary structure
- Called preprocollagen
- Primary structure is a repeating sequence of Gly-X-Y, where X and Y can refer to proline, hydroxyproline or hydroxylysine.
- Glycine is the most abundant amino acid in collagen because it is reliably 1/3 of the primary structure.
- This also means if they ask you which amino acid is most reflective of collagen content of a tissue, the answer is glycine.
- The mere translation of glycine-X-Y repeats occurs at the rough endoplasmic reticulum.
Hydroxylation occurs next
- Creates hydroxylated preprocollagen
- Increases hydrogen bonding between primary Gly-X-Y polypeptides
- Requires vitamin C as a cofactor
- Contributes to secondary structure (H-bonding)
- Osteogenesis imperfecta (↓ collagen I) leads to defective hydrogen bonding
Then glycosylation
- Creates glycosylated + hydroxylated preprocollagen
- Strengthens bonding between polypeptides
- Contributes to tertiary structure
- More disulfide bonds form between polypeptides
Triple helix can now spontaneously form
- Preprocollagen now bears the adequate thermodynamics to spontaneously spin into a triple helix.
- This triple helical form is now called procollagen.
Procollagen is then exocytosed from the cell
- In the extracellular space, the procollagen has disulfide-rich non-helical end-groups that require cleavage.
Non-helical end-groups are cleaved from procollagen
- Procollagen peptidase (aka propeptidase) then proteolytically cleaves off these terminal regions, thereby decreasing the procollagen’s solubility in water ~1000-fold.
- If these regions are not cleaved off, ↑ H2O solubility weakens collagen.
- Once these N- and C-terminal non-helical regions are cleaved off, the procollagen is now called tropocollagen.
- Ehlers-Danlos syndrome (usually ↓ collagen III) can also be caused by deficiency of procollagen peptidase.
Tropocollagen then arranges into closely packed collagen fibrils
- Tropocollagen molecules then align to form collagen fibrils
Collagen fibrils are then crosslinked to become mature collagen fibers
- Collagen fibrils are crosslinked via lysyl oxidase to make mature collagen.
- Lysyl oxidase is a copper-dependent enzyme.
- Lysyl oxidase creates aldehydes from the -OH groups. The aldehydes can then crosslink.
- Menkes syndrome leads to ↓ activity of lysyl oxidase because of copper deficiency.
- (The Menkes syndrome post is here).
| Loss of aesthetics 2° to aging (wrinkles) is caused by ↓ collagen fibril production. All collagen end-products ↓ with aging. Crosslinking is unaffected. |
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