Biochemistry · Topic
Collagen synthesis !
Collagen is built in steps inside and outside the cell; each step needs an enzyme or a vitamin, and each failure causes a different disease.
Updated 2026-11-01
Key facts
- Inside the fibroblast: translation on the RER, hydroxylation of proline and lysine, glycosylation of hydroxylysine and triple-helix formation (procollagen).
- Prolyl and lysyl hydroxylases need vitamin C, Fe²⁺, O₂ and α-ketoglutarate; without vitamin C the helix is unstable (scurvy).
- Outside the cell: procollagen peptidases cleave the N- and C-propeptides (tropocollagen), which assembles into fibrils.
- Lysyl oxidase (copper-dependent) forms the cross-links that give strength; it fails in Menkes disease and lathyrism.
- Repeating Gly–X–Y sequence: glycine sits every third residue because it is the only one that fits the centre of the triple helix; X is often proline and Y hydroxyproline.
In detail
- 1. Pro-α chains are made on ribosomes of the rough endoplasmic reticulum; the signal peptide is removed.
- 2. Hydroxylation of prolines (prolyl 4-hydroxylase) and lysines (lysyl hydroxylase, PLOD1 gene); vitamin C is the cofactor that keeps the iron reduced.
- 3. Glycosylation of some hydroxylysines with galactose and glucose.
- 4. Three chains line up through their C-propeptides (disulfide bonds) and wind from the C end to the N end: the procollagen triple helix. It leaves via the Golgi in vesicles.
- 5. Outside the cell, N-proteinase (ADAMTS2) and C-proteinase remove the propeptides, leaving tropocollagen.
- 6. Tropocollagen molecules self-assemble into staggered fibrils, which bundle into fibres.
- 7. Copper-dependent lysyl oxidase turns lysines and hydroxylysines into aldehydes that form covalent cross-links between neighbouring molecules.
Memory aid
Main types: I = bone, skin and tendon; II = cartilage (“car-TWO-lage”); III = reticular fibres and vessels; IV = basement membrane (“four on the floor”).
- Also called
- Collagen biosynthesis, Procollagen
Clinical notes
- Scurvy (step 2 fails): bleeding gums, perifollicular petechiae, poor wound healing and corkscrew hairs.
- Osteogenesis imperfecta (step 1, type I collagen) and Ehlers–Danlos syndrome (steps 1, 2 or 5, depending on type) are inherited defects of this pathway.
- Menkes disease (no copper for lysyl oxidase): kinky hair, fragile arteries and neurological damage in infant boys.
Related conditions
Related
- Collagen
- Hydroxyproline
- Vitamin C (ascorbic acid)
- Copper
- Elastin
- Fibrillin-1
- Iron
- Protein structure and folding
Test yourself
Think of the answer, then tap the question to see it.
Why does vitamin C deficiency cause scurvy?
Prolyl and lysyl hydroxylases need vitamin C; without hydroxyproline the triple helix is unstable and collagen is degraded.
Why does glycine appear every third amino acid in collagen?
It is the only amino acid small enough to fit the tight centre of the triple helix.
Which copper-dependent enzyme forms collagen cross-links?
Lysyl oxidase; without copper (Menkes) the fibres stay weak and arteries become fragile.
Which steps of synthesis happen outside the cell?
Cleavage of the N- and C-propeptides, assembly into fibrils and cross-linking by lysyl oxidase.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Collagen biosynthesis and modifying enzymes (Reactome, 2026); Crosslinking of collagen fibrils (Reactome, 2026); PLOD1 gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); ADAMTS2 gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).
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Representative model, for educational purposes only.