Synthesis Of Collagen & Insulin Flashcards
What is the main role of collagen in the body?
- Most abundant protein in the body (25-35%)
- Most abundant fibrous protein in connective tissue
- Provides structure and support of tissues and organs
- Tendons, ligaments, cartilage, bone
What type of cells produce and secrete collagen?
Fibroblasts (in connective tissue)
Describe the structure of collagen fibres
- Basic unit is TROPOCOLLAGEN
- 300nm rod shaped protein
- 3 polypeptide α chains twisted into a right handed triple helix
- GLY - X - Y repeating structure
- Each polypeptide chain is ~1000 AA long
What are the structural advantages of the triple helix structure of collagen?
- Non extensible
- Non compressible
- High tensile strength
What bonds are present within the 3 polypeptide chains?
H bonds between α chains
Which amino acids are most abundant in collagen?
- Glycine
- Proline/Hydroxyproline
- Arginine
- Lysine
List 2 things needed for the activation of PROLYL HYDROXYLASE
- Vitamin C
- Fe2+ ions
Explain why a lack of vitamin C can cause scurvy
- Vitamin C needed for the activation of prolyl hydroxylase
- Inhibition of prolyl hydroxylase means less hydroxylation of Pro residues on procollagen
- Less OH groups means less H bonds between tropocollagen fibrils so weakened tropocollagen triple helices
- Connective tissue defects
Why is tropocollagen cleaved outside of the cell?
Covalent cross linking of tropocollagen would occur inside cell and destroy it
What is needed for the activation of lysyl oxidase?
- Vitamin B6
- Cu2+ ions
Explain how cross linking between tropocollagen molecules occurs
- Covalent cross links between Lysine residues using LYSYL OXIDASE
- Spontaneous bonding between aldehyde derivatives forming ALDOL CROSS LINKS
Explain the type of bonding present in collagen molecules
- H bonding between α chains (3 together form tropocollagen)
- Covalent cross links between tropocollagen molecules forming collagen fibrils
- Aggregations of collagen fibrils form collagen fibres
Explain why collagen has a striated appearance under a microscope
- Lateral association of tropocollagen molecules and cross linking forms OVERLAPPING
- Lighter staining regions with no overlap
- Darker staining regions where gaps are (dye fills the gaps)
What can cause Ehlers-Danlos syndrome?
- Mutation in collagen type V
- Lysyl oxidase deficiency
Explain how the cell prevents collagen cross linking inside the cell
Secretion of LYSYL OXIDASE out of cell which is required for the cross linking of tropocollagen molecules
Describe the formation of procollagen in the RER
- Preprocollagen synthesised in ribosomes contains N terminal signal peptide
- SRP recognises signal peptide and directs preprocollagen towards RER cisternae
- Preprocollagen enters RER and signal peptide is CLEAVED by signal peptidase enzyme forming procollagen
Explain the modifications that take place in the RER of procollagen
- Hydroxylation of PROLINE and LYSINE residues to form HYDROYPROLINE and HYDROXYLYSINE
- PROLYL HYDROXYLASE
- Addition of N linked oligosaccharides to Arg residues
- Addition of GALACTOSE to hydroxylysine residues
Describe the formation of tropocollagen from procollagen secreted from the Golgi
- Modified procollagen secreted from Golgi into a transport vesicle
- Procollagen vesicle travels to plasma membrane and is exocytosed from cell
- N and C termini of procollagen are cleaved by SPECIFIC ENDOPEPTIDASES forming tropocollagen
Where in the cell does the formation of the triple helix of procollagen occur?
RER
Describe how the association of tropocollagen molecules leads to the formation of a collagen fibre
- Lateral association of tropocollagen molecules
- Overlapping (striated appearance)
- Covalent cross linking between Lys residues on adjacent tropocollagens catalysed by LYSYL OXIDASE
- Spontaneous ALDOL cross linking between aldehyde derivative groups forming collagen FIBRIL
- Aggregations of fibrils form FIBRES
