C. Cross linkage
D. All of the above
Ans:D. All of the above.
Collagen Structure is shown in the image.
BIOSYNTESIS OF COLLAGEN
- The polypeptide precursors of the collagen molecule are formed in fibroblasts (or in the related osteoblasts of bone and chondro blasts of cartilage), and are secreted into the extracellular matrix.
1. Formation of pro-α chains:
- The newly synthesized polypeptide precursors of α chains(prepro-α chains) contain a special amino acid sequence at their N-terminal ends.
- This sequence acts as a signal that targets the polypeptide being synthesized for secretion from the cell.
- The signal sequence facilitates the binding of ribosomes to the rough endoplasmic reticulum (RER), and directs the passage of the prepro-α chain into the lumen of the RER.
- The signal sequence is rapidly cleaved in the RER to yield a precursor of collagen called a pro-α chain
- Proline and lysine residues found in the Y-position of the –Gly–X–Y– sequence can be hydroxylated to form hydroxyproline and hydroxylysine residues.
- These hydroxylation reactions require molecular oxygen,Fe2+, and the reducing agent vitamin C without which the hydroxylating enzymes, prolyl hydroxylase and lysyl hydroxylase, are unable to function .
- In the case of ascorbic acid deficiency (and, therefore, a lack of prolyl and lysyl hydroxylation), interchain H-bond formation is impaired, as is formation of a stable triple helix.
- Additionally, collagen fibrils cannot be cross-linked ,greatly decreasing the tensile strength of the assembled fiber. The resulting deficiency disease is known as scurvy.
3. Glycosylation: Some hydroxylysine residues are modified by glycosylation with glucose or glucosyl-galactose .
4. Assembly and secretion: After hydroxylation and glycosylation, pro-α chains form procollagen, a precursor of collagen ,
- The formation of procollagen begins with formation of interchain disulfide bonds between the C-terminal extensions of the pro-α chains.
- This brings the three α chains into an alignment favorable for helix formation.
- The procollagen molecules move through the Golgi apparatus, where they are packaged in secretory vesicles.
- The vesicles fuse with the cell membrane, causing the release of procollagen molecules into the extracellular space.
5. Extracellular cleavage of procollagen molecules: After their release, the procollagen molecules are cleaved by N- and C-procollagen
peptidases, which remove the terminal propeptides, releasing triple-helical tropocollagen molecules.
6. Formation of collagen fibrils: Individual tropocollagen molecules spontaneously associate to form collagen fibrils. They form an ordered, overlapping, parallel array, with adjacent collagen molecules arranged in a staggered pattern, each overlapping its neighbor by a length approximately three-quarters of a molecule .
7. Cross-link formation: The fibrillar array of collagen molecules serves as a substrate for lysyl oxidase.
- This Cu2+-containing extracellular enzyme oxidatively deaminates some of the lysyl and hydroxylysyl residues in collagen.
- The reactive aldehydes that result (allysine and hydroxyallysine) can condense with lysyl or hydroxy -lysyl residues in neighboring collagen molecules to form covalent cross-links and, thus, mature collagen fibers