[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Biochemistry](https://durgical.com/en/biochemistry/) › Collagen synthesis [Biochemistry](https://durgical.com/en/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 - [Osteogenesis imperfecta](https://durgical.com/en/conditions/osteogenesis-imperfecta/) - [Ehlers–Danlos syndrome](https://durgical.com/en/conditions/ehlers-danlos-syndrome/) - [Scurvy (vitamin C deficiency)](https://durgical.com/en/conditions/scurvy/) - [Menkes disease](https://durgical.com/en/conditions/menkes-disease/) ## Related - [Collagen](https://durgical.com/en/biochemistry/enzymes/collagen/) - [Hydroxyproline](https://durgical.com/en/biochemistry/molecules/hydroxyproline/) - [Vitamin C (ascorbic acid)](https://durgical.com/en/biochemistry/molecules/vitamin-c/) - [Copper](https://durgical.com/en/biochemistry/topics/copper/) - [Elastin](https://durgical.com/en/biochemistry/enzymes/elastin/) - [Fibrillin-1](https://durgical.com/en/biochemistry/enzymes/fibrillin-1/) - [Iron](https://durgical.com/en/biochemistry/topics/iron/) - [Protein structure and folding](https://durgical.com/en/biochemistry/topics/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. [Add to my cards (4)](https://durgical.app/estudiar/?add=/en/biochemistry/topics/collagen-synthesis/) Educational information, not medical advice. For any symptom, see a health professional. Sources: [Collagen biosynthesis and modifying enzymes](https://reactome.org/PathwayBrowser/#/R-HSA-1650814) (Reactome, 2026); [Crosslinking of collagen fibrils](https://reactome.org/PathwayBrowser/#/R-HSA-2243919) (Reactome, 2026); [PLOD1 gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/plod1/) (MedlinePlus, US National Library of Medicine, 2026); [ADAMTS2 gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/adamts2/) (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). [← All of biochemistry](https://durgical.com/en/biochemistry/) ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/biochemistry/topics/collagen-synthesis/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/biochemistry/topics/collagen-synthesis/