SESSION 16 Flashcards
Define collagen
The most abundant protein in the body
Most fibrous protein in connective tissue:
- tendons, ligaments, cartilage and bone
- loose connective tissue providing structure to internal organs
Secreted by fibroblasts in connective tissue
Describe the structure of the triple- stranded collagen helix
The basic unit of collagen is tropocollagen
Primary sequence is (Glycine- x- Y)n
- mostly proline or hydroxyproline in X and Y positions
- glycine in every third position
Collagen made of 3 polypeptide chains:
- 2 x a chains
- left handed triple helix
Hydrogen bonds between alpha chains stabilise the structure
- proline residues: correct geometry for the extended a -chain conformation. Prevents the peptide from assuming another shape
- hydroxyproline residues are formed from proline residues by the enzyme Prolyl Hydroxylase. This increases the amount of inter- chain H- bonds
- Prolyl Hydroxylase require vitamin C and iron for activity
What are the features of the left handed triple helix of collagen?
Non- extensible -> stretched out as much as possible
Non- compressible -> can’t squash
High tensile strength -> ligaments and cartilage
State the different types of collagen
Skin -> type I (2 alpha 1 chains & 1 alpha 2 chains)
Cartilage/ Connective tissue -> type II
Arteries (cardiovascular system) -> type III
Basement membrane -> type IV
Describe the synthesis and modification of collagen in the ER
- targeted to ribosome
- signal peptide cleaved AA’s enters ER lumen
- hydroxylate proline and lysine residues (addition of OH)
- prepro a chain -> pro a chain (action of signal peptide)
- Glycosylation- add sugar (galactose and glucose)
- pro- collagen formed- 3 strand triple helix, with the aid of the enzyme prolyl hydroxylase
- procollagen secreted to the Golgi
What is the role of Prolyl hydroxylase?
- associated with PDI in the ER
- coenzyme- requires vitamin C and iron for activity
- allows increased hydrogen bonding to stabilise the helix
- scurvy is due to weak tropocollagen triple helices
Define scurvy
Scurvy is a disease caused by a deficiency of Vitamin C, characterised by swollen bleeding gums and the opening of previously healed wounds
Lack of strength of collagen
Describe the synthesis and modification of Collagen in the Golgi
- chain alignment, formation of disulphide bonds
- formation of triple helical procollagen from C to N terminus (prevents larger subunits being made)
- further glycosylation
- procollagen secreted into a vesicle to be transported into the extracellular matrix
Describe the synthesis and modification of Collagen in the extracellular matrix
- procollagen enters the extracellular space via exocytosis
- procollagen is converted to tropocollagen
- removal of N and C terminal pro-peptides
- by procollagen peptidase
- tropocollagen is very insoluble
- lateral association (aggulation) collagen molecules followed by covalent cross links
- hydroxylysine used for the cross links with the aid of Lysol oxidase as the enzyme
Aggregation of fibrils
Describe the roe of Lysyl oxidase
- extracellular
- requires vitamin B6 and copper ions for activity
- forms covalent cross- links
Why is tropocollagen secreted before processing occurs?
Protection mechanism
The cell would otherwise be destroyed -> burst
Provide an overview of collagen biosynthesis
- tropocollagen subunits are synthesised as Preprocollagen
- pre- hydrophobic signal sequence marks protein for secretion
- pro- subunits synthesised with N and C terminal peptides. This prevents the formation of collagen fibres inside cells
- procollagen is secreted from cells by exocytosis
- procollagen peptidase s then cleaves the N and C terminal peptides (extracellular)
- collagen subunits (tropocollagen) form covalent cross- links
- lysine residues -> aldehyde derivates by the enzyme Lysyl oxidase
- aldehyde derivatives then spontaneously form Algol cross- links
- lysyl oxidase required vitamin B6 and copper ions for activity
Define Ehlers- Danlos syndrome
Mutation in collagen type V or lysyl oxidase deficiency
Define osteogenesis imperfecta
An inherited disorder characterized by extreme fragility of the bones.
