Collagen synthesis: Quick review
- Collagen synthesis happens in Fibroblasts and Extra cellular matrix (ECM).
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Steps inside Fibroblast
- The Pre-Pro α collagen chain is formed by ribosomes on RER (rough endoplasmic reticulum). The process is called translation (mRNA to Protein formation).
- This newly formed chain has Glycine-X-Y- Glycine-X-Y- Glycine-X-Y sequence, where X is any other amino acid and Y is Proline. 1/3 of collagen is Glycine.
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- This Pre-Pro α collagen chain undergo extensive Post Translation modification in Fibroblast and ECM to form Collagen Fibril.
Step 1: Splitting of signal peptide
- The signal peptide from one terminal of Pre-Pro α collagen chain is clipped in RER lumen and now called Pro α collagen chain.
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Step 2: Hydroxylation
- Randomly selected Lysine and Prolysine will undergo hydroxylation in presence of Lysyl and Prolyl hydroxylase (Ascorbate/ Vit C is cofactor). Deficiency of Vitamin C causes Scurvy, where collagen synthesis is faulty and leads to gum bleeding and fragile tissues.
- The hydroxylation process is essential part of incorporating more hydrogen molecules in Pro α collagen chain, so that there are more hydrogen bonds between different α chains. More hydrogen bonds mean stronger Triple helix.
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Step 3 Formation of triple helix
- Soon after hydroxylation there is formation of hydrogen and disulphide bonds in between three Pro α collagen chains giving rise to rope like tertiary structure of collagen also called Procollagen (Triple Helix).
Step 4 Glycosylation
- Procollagen molecule moves into Golgi complex of fibroblast where it is Glycosylated (glucose and galactose are added to lysine and hydroxylysine).
Step 5 Exocytosis from Fibroblast
- The Glycosylated Triple helix (Procollagen) is exocytosed by secretory vesicle into ECM.
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In ECM
Step 6 Proteolytic Processing
- C terminus and N terminus Procollagen Peptidase cleaves bulky disulphide rich terminal region of Procollagen. This process transforms soluble Procollagen into insoluble Tropocollagen.
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Step 7 Cross-Linking
- Lysine and hydroxylysine residues of Tropocollagen undergo oxidative deamination in the presence of Lysyl oxidase. Lysyl oxidase is copper dependent enzyme. There will be Cross-linking between groups of tropocollagen molecules to form collagen fibril. This final collagen fibril has tensile strength of steel wire and it is abundantly present in human body in different forms.
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- Hope you got basic understanding of collagen synthesis here, heritable connective tissue disorders are next in line and hopefully now you will get better understanding of disorders related to defective collagen synthesis.
- Revision for today https://creativemeddoses.com/topics-list/collagen-the-introduction-and-type/
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