Biochemistry of the ECM Flashcards
What type of molecule s collagen
A protein
What is the structure of collagen
It has a triple helical structure.
How does a single collagen chain become the triple helix structure
Three single left handed collagen fibres twist together to create a right handed triple helix.
What are the two major amino acids which make up collagen
Glycine and proline
What is the general formula for the amino acid make-up of collagen
(Glyc-X-Y)n - every third amino acid is glycine, the other two tend to be prolines.
What type of proline tends to make up the amino acid chain of collagen alongside glyceine
3-hydroxyproline and 4-hydroxyproline.
Why are glycine and proline the amino acids making up collagen
Because these are small amino acids - there is only space for small amino acids and these allow tight packing.
Why is collagen nutritionally poor
Hydroxyproline is unstable and it is deficient in other amino acids.
What are the three chains that wind together to make a collagen molecule
The three chains can be identical or non-identical.
In which type of collagen are the chains non-identical
Type I
In which types of collagen are the chains identical
Type II, III and IV.
What are the three chains which make up type one collagen
2 alpha 1 chains and 1 alpha 2 chain.
Where is type I collagen found
Bone, tendon, skin, lung, cornea, arteries
Where is type II collagen found
Cartilage.
Where is type III collagen found
Skin, lung, uterus, arteries, ligaments.
Where is type IV collagen found
Basement membranes
Towards which terminal do collagen chains associate
The C terminal
What is required in order for individual collagen chains to wind together into a triple helix
Hydroxylation
What is the process of the formation of a collagen fibril
Individual collagen chains associated at C termini. They then undergo hydroxylation and glycosylation and wind together to form a triple helix. The triple helix is extruded from the cell and the N and C termini are cleaved to form a tropocollagen molecule. Tropocollagen molecules are then cross-linked to form a collagen fibril.
What kind of structure do elastin fibres form (like how collagen fibres form a triple helix)
A mesh
What is the name of the structures which link three or four elastin chains together
Desmosines.
What is the structure of elastin fibres
There is an elastin core surrounded by micro-fibrils.
What is the relationship between elastin fibres and emphysema
Elastin can be degraded by extracellular proteinases released by neutrophils in the inflammatory response. This can lead to emphysema where alveolar walls are broken down.
What is the role of alpha 1 antitrypsin
Alpha 1 antitrypsin has a role in inhibiting the extracellular proteinases released by neutrophils in the inflammatory response to prevent the degradation of elastin.
What is the impact of mutation and cigarette chemicals (oxidants) on alpha-1 antitrypsin
Mutations and oxidants can prevent the action of alpha 1 antitrypsin meaning that the proteinases are free to degrade elastin.
What is the structure of PGs in cartilage
PGs are made up of glycoaminoglycans. These are acidic, sulphated and negatively charged. The negative charges attract anions which bring water and this means PGs are very hydrated.
What happens to proteoglycans when they are compressed
Water is extruded
Mutations closer to which end of collagen fibrils have the greatest impact
Mutations closer to the C termini have greater impact because collagen molecules wind up from the C termini.
What are the three components of bone
- Organic component - mostly collagen type I
- Inorganic salts
- Water
What is the inorganic component of bone
Hydroxyapitite
What are the stages of bone deposition
First the collagen matrix is laid down. The inorganic hydroxyapatite is laid on top and mineralises.
What are two causes of poor mineralisation of bone
- Vitamin D deficiency
- Chronic metabolic acidaemia
What are the three components of the crystal lattice of hydroxyapatite
- OH-
- Ca2+
- PO4^3-
What are three nutritional and genetic diseases of collagen synthesis
- Vitamin C deficiency (scurvy)
- Osteogenesis imperfecta (brittle bone disease)
- Ehler’s Danlos Syndrome.
What is the cause of collagen defect due to vitamin C deficiency
Reduced hydroxylation
What is the cause of the collagen defect in osteogenesis imperfecta type I
Decreased type I collagen levels
What is the cause of the collagen defect in osteogenesis imperfecta type II
Abnormal type I collagen.
What is marfan syndrome
A connective tissue disorder. This is a mutation in the fibrillin 1 gene on chromosome 15.
In marfan syndrome, levels of what increase?
TGF beta.
