This document discusses collagen biochemistry. It covers the distribution of collagen in nature, the key collagen types, and collagen biosynthesis. Collagen biosynthesis involves post-translational modifications like lysine and proline hydroxylation. Collagen undergoes intracellular and extracellular processing, including removal of propeptide extensions and cross-linking by lysyl oxidase to form mature collagen fibers essential for tissue structure and integrity. Disorders like Ehlers Danlos syndrome result from defects in these collagen processing steps.

1. Collagen Biochemistry

2. This lecture will cover Collagen as a vital connective tissue protein Distribution of collagen in nature The key collagen types Collagen biosynthesis Collagen cross-linking and stabilisation

3. Most of us are probably aware that collagen is a widely used cosmetic agent.

5. Collagen is the most abundant protein in the animal kingdom

6. Major collagen types

7. Collagen is essential for maintaining tissue integrity

8. What’s the proof?

10. Collagen biosynthesis Intracellular events

11. Collagen hierarchy

12. Intracellular processing

13. Collagen undergoes post-translational modification Lysine and proline hydroxylation Result from lysyl & prolyl hydroxylase action, ferrous iron, oxygen & ascorbate Residues provide stability In case of OH-lysine, they serve as glycosylation sites and cross-linking sites OH-lysine glycosylation Glucosyl & galactosyl transferases May aid in collagen shipment to ECS

14. Extracellular processing

15. Extracellular modifications N & C-propeptide extensions are removed N & C-procollagen proteinases Reduces solubility, enables fibril formation Optimises subsequent cross-linking

16. Ehlers Danlos Highly elastic skin In rare cases it can be fragile Chronic joint pain, joint laxity Scoliosis Increased risk of bone fracture Fragile blood vessels Mitral valve prolapse

17. Extracellular processing II Collagen cross-linking

19. Lysyl oxidase initiates cross-link formation Copper containing amine oxidase Converts the  -amino group of lysine and hydroxylysine to corresponding aldehydes

20. Lathyritic agents underpin the critical importance of collagen cross-links  -aminoproprionitrile

21. The cross-links of bone & dentine collagen The lysyl and hydroxylysyl aldehydes react with adjacent  -amino groups of other lysine/hydroxylysine residues – KETOAMINES Bivalent cross-links, 1 st phase cross-links Ketoamines converted to trivalent or 2 nd phase cross-links by reaction with another lysyl/hydroxylysyl aldehyde Pyrrole & pyridinium cross-links

22. Pyrrole & Pyridinium Cross-links