Collagen Flashcards
What is collagen?
Collagen is a family of fibrous proteins. Collagen forms insoluble fibres with a high tensile strength.
What are the 3 main groups collagen molecules can be categorised into?
- Fibril-forming collagen - Type I, II, III. Involved in the formation of bone and tendons. It is the most abundant.
- Network Forming collagen - Type VI and VII.
Involved in the making of the basal lamina. - Fibril-associated collagen - Involved in other types. Can be involved in cross-linking.
What is the structure of Collagen? i.e. give details of the primary, secondary and quaternary structure.
- Primary - Long chain of amino acid. Glycerine makes up every third amino acid. It has a repetitive sequence. Proline is usually the second amino acid and hydroxyproline the third.
- Each molecule of collagen is then coiled into a left-hand helix.
- Each pro collagen triple helix is then coiled with 2 others in a right hand helix to form a tropocollagen molecule.
How is collagen synthesised? Give details form polypeptide synthesis to a collagen fibril.
Collagen is first transcribed and translated in a fibroblast. Then post-translational modifications can occur. The amino acids undergo hydroxylation. Sugar side chains are added. The pro collagen triple helix then moves out the fibroblast into the extracellular space. Here extension peptides are removed. A tropocollagen molecule is then synthesised spontaneously. This then aggregates into a microfibril which crosslinks to collagen fibril.
Give the unique properties of the collagen primary structure.
- It has a high glycine content (33%)
- It has a high proportion of covalently modified e.g. 5-hydroxylysine and 4-hydroxyproline
- It has 3.3 amino acids per turn
What is pro-collagen?
Collagen is translated in an inactive form. It has extension peptides on the end of the molecule. These are removed by peptidases. These can form sulphide bridges to stabilise the collagen molecules. These disulphide bridges hold the 3 chains relative to each other.
What is Allysine? What is it’s purpose?
Lysine is covered to Allysine by the removal of the amine group via the enzyme Lysyl oxidase. It can form hydrogen bonds with other Allysine molecules or Lysine molecules to form the hydrogen bonds between the chains. These are known as cross-links that stabilise the collagen.
Why is there a high glycine content in collagen?
Due to the tight coiling of collagen, some amino acids have their side chains on the inside of the coil. Glycine is the only amino acid whose side chain will fit. Common mutations result in glycine being replaced with an amino acid with a larger side chain. This therefore means the collagen molecule cannot coil as tightly and it is destabilised.
What is Vitamin C crucial for?
Vitamin C is a cofactor for the enzyme Propyl hydroxylase and Lysyl hydroxylase. These hydroxylate the amino acids proline and lysine. The hydroxylated versions of these amino acids form hydrogen bonds and therefore the crosslinks to stabilise the molecule. Hydroxylysine is also glycoserated - these form crosslinks.
What form the nucleation sites?
The gaps between the collagen chains. Calcium phosphate is then deposited run the nucleation sites. Calcium phosphate reinforces the collagen. The nucleation sites are at regular intervals and so there is even distribution of calcium phosphate. This produces rigid bone.
Why would collagen need to be broken down? What family of enzymes break down collagen?
- During growth and tissue remodelling must occur
- During tissue repair e.g. scarring
Collagenases break down collagen. These enzymes use metals and so are known as metalloproteinases. These enzymes are used in tumour invasion and metastasis.
What is Dupuytren’s contracture?
Long term syndrome. Occurs when excess collagen is deposited in the palm of the hand. This slowly causes the tendons in the hand to contact. The ring finger and little finger then fold over and are difficult to move. This leads to a lack of movement in the hand. Usually treated with surgery or a needle to interfere with collagen formation. It is now under trail to use colleganses to break down the excess collagen.
What is Osteogenesis imperfecta and how what is its cause?
It is a disease that leads to an increased risk of bone fracture. It has a genetic cause but may not necessarily be passed on form parent to child. Severity of the syndrome depends on the nature of the mutation.
What is Elhers Danlos syndrome?
A series of rare inherited genetic diseases that affect collagen. An example of this is Type VI in which there is a deficiency in lysyl oxidase - and so allysine is not produced. As a result crosslinks cannot form and so collagen is not reinforced.
What is scurvy? What is the biochemical cause?
A severe vitamin C deficiency. As a result propyl hydroxylase and lysyl hydroxylase cannot work. The amino acids in the primary structure are not hydroxylated. Crosslinks cannot form and the the collagen is not reinforced. Symptoms include bleeding gums, loose teeth, spongy/swollen purple gums, joint pain, fatigue, poor healing and bulging eyes. Left untreated it can be fatal as it can lead to bleeding in the heart muscle.
