Collagen Flashcards
What functions does collagen have (4)
- Forms resilient sheets that support the skin and internal organs
- Forms molecular cables that strengthen the tendons
- Forms molecular cables that strengthen bones
- Bones and teeth are made by adding hydroxyapatite crystals to collagen
What is collagen?
glue
25% of total body protein
major structural protein in extracellular matrix
What is the primary structure of collagen?
- A repeated sequence of three amino acids forms the sturdy structure
- proline and hydroxyproline are frequent in the amino acid chain
What amino acid is every third one for the primary structure of collagen?
Glycine (neutral & small)
How long is each alpha chain?
Each chain is over 1400 amino acids long and up to 3000
How does collagen form its helix?
Collagen triple helix
- Each polypeptide chain forms a left handed helix (3.3 residues per turn)
- Triple helix is formed (tropocollagen) with a right handed twist
- Small glycine residues pack into the centre
- Pro & Hyp residues on the outside to max hydrogen bonds
What chains does collagen 1 have?
2x chains of COL1a1
1x chain of COL1a2
Why can collagens have different functions?
All collagens are triple helixes but type (sequence of the alpha helix) and organisation (cross linking) can confer different function
What happens to collagen with aging?
As collagen ages more crosslinking occurs- collagen becomes less elastic, & more brittle + synthesis decreases
- Bones more easily broken
- Arteries and skin become less elastic
What is Fibrosis?
- Fibrosis is defined by the overgrowth, hardening, and/ or scarring of various tissues and is attributed to excess deposition of extracellular matrix components including collagen
What is associated with Fibrosis?
- Aging or disease are often associated with fibrosis- deleterious for the tissue function
- Not only due to collagen, but collagen is one of the unregulated genes in fibrotic tissue
How many different types of collagen are there?
12 different types of collagen
What makes types of collagen different?
Different alpha chain combination and quaternary structure
What are the most common types of collagen?
Types I, II & III
- form long fibrils (fibril forming collagens)
What do types IV & VI form?
- a 2-dimensional matrix= important in basal lamina (network-forming collagens)
What is type I?
90% of the total collagen, main component in bone- found in skin, hair, tissues- not found in cartilage- used in tissue repair
What is Type II?
Main component of cartilage- found in cornea and vitreous humour
What is type III?
Combines with type I- found in tissues with elastic properties/ hollow organs: skin, arteries, muscle, lungs, intestine
What other types of collagen may be involved in crosslinking?
V, IX, XII
What are Fibroblasts?
Specialised cells according to where they are
Encode different alpha chains that will form different collagen molecules
What are 4 examples of Fibroblasts?
Osteoblasts
Chondroblasts
Dermal fibroblasts
Cardiac fibroblasts
What are the 6 steps in collagen biosynthesis?
- Pro a-chain backbone (Gly-X-Y)
- Hydroxylation of proline and lysine (requires vitamin C)
- Glycosylation
- Exocytosis
- Cleavage of procollagen C & N terminals
- Formation of cross links- copper dependent
What stabilises cross links in collagen?
Lysyl oxidase (copper dependent)
Uses copper as a cofactor
What is the Hydroxylation of proline and lysine (Step 2)
- Enzymes involved are prolyl hydroxylase and lysyl hydroxylase
- Reaction requires Vit C to assist in the addition of oxygen (from diet)
