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IMS- Strand 2 > Collagen > Flashcards

Collagen Flashcards

1
Q

What functions does collagen have (4)

A
  • 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
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2
Q

What is collagen?

A

glue
25% of total body protein
major structural protein in extracellular matrix

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3
Q

What is the primary structure of collagen?

A
  • A repeated sequence of three amino acids forms the sturdy structure
  • proline and hydroxyproline are frequent in the amino acid chain
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4
Q

What amino acid is every third one for the primary structure of collagen?

A

Glycine (neutral & small)

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5
Q

How long is each alpha chain?

A

Each chain is over 1400 amino acids long and up to 3000

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6
Q

How does collagen form its helix?

A

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

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7
Q

What chains does collagen 1 have?

A

2x chains of COL1a1
1x chain of COL1a2

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8
Q

Why can collagens have different functions?

A

All collagens are triple helixes but type (sequence of the alpha helix) and organisation (cross linking) can confer different function

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9
Q

What happens to collagen with aging?

A

As collagen ages more crosslinking occurs- collagen becomes less elastic, & more brittle + synthesis decreases
- Bones more easily broken
- Arteries and skin become less elastic

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10
Q

What is Fibrosis?

A
  • 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
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11
Q

What is associated with Fibrosis?

A
  • 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
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12
Q

How many different types of collagen are there?

A

12 different types of collagen

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13
Q

What makes types of collagen different?

A

Different alpha chain combination and quaternary structure

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14
Q

What are the most common types of collagen?

A

Types I, II & III
- form long fibrils (fibril forming collagens)

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15
Q

What do types IV & VI form?

A
  • a 2-dimensional matrix= important in basal lamina (network-forming collagens)
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16
Q

What is type I?

A

90% of the total collagen, main component in bone- found in skin, hair, tissues- not found in cartilage- used in tissue repair

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17
Q

What is Type II?

A

Main component of cartilage- found in cornea and vitreous humour

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18
Q

What is type III?

A

Combines with type I- found in tissues with elastic properties/ hollow organs: skin, arteries, muscle, lungs, intestine

19
Q

What other types of collagen may be involved in crosslinking?

A

V, IX, XII

20
Q

What are Fibroblasts?

A

Specialised cells according to where they are
Encode different alpha chains that will form different collagen molecules

21
Q

What are 4 examples of Fibroblasts?

A

Osteoblasts
Chondroblasts
Dermal fibroblasts
Cardiac fibroblasts

22
Q

What are the 6 steps in collagen biosynthesis?

A
  1. Pro a-chain backbone (Gly-X-Y)
  2. Hydroxylation of proline and lysine (requires vitamin C)
  3. Glycosylation
  4. Exocytosis
  5. Cleavage of procollagen C & N terminals
  6. Formation of cross links- copper dependent
23
Q

What stabilises cross links in collagen?

A

Lysyl oxidase (copper dependent)
Uses copper as a cofactor

24
Q

What is the Hydroxylation of proline and lysine (Step 2)

A
  • Enzymes involved are prolyl hydroxylase and lysyl hydroxylase
  • Reaction requires Vit C to assist in the addition of oxygen (from diet)
25
Q

What does hydroxyproline do?

A

Stablility of the triple helix due to extra H bonds

26
Q

What does Hydroxylysine do?

A

Stability of the fibrils due to extra cross linking

27
Q

What is Osteogenesis Imperfecta?

A

Mutation in collagen chains

28
Q

What is Scurvy?

A

Lack of vitamin C in diet leading to reduced hydroxylation of proline and lysine residues= less crosslinking of collagens

29
Q

What is Menke’s disease? (Affects stage 6)

A

copper deficiency

30
Q

What is Ehlers- Danlos syndrome type VI?

A

Lysyl oxidase deficiency

31
Q

What is Osteogenesis imperfecta also known as?

A

Brittle bones disease

32
Q

How does Osteogenesis imperfecta arise?

A
  • Spontaneous mutation (no fam history to suggest a genetic disorder)
  • Severity increases with substitution by large and charged amino acids
33
Q

What are the most common subtypes of Osteogenesis Imperfecta?

A

I- IV (sometimes mistaken for child abuse)

34
Q

What is Type 1 (OI)

A

Mild, non-deforming
Sclera= blue
LE= normal

35
Q

What is Type 2 (OI)

A

Perinatal lethal
Sclera= blue
LE= Perinatal

36
Q

Type 3 (OI)

A

Progressively deforming
Sclera= Blue then normal
LE= Childhood

37
Q

Type 4 (OI)

A

Moderately deforming
Sclera= Normal
LE= Slight reduction

38
Q

What is scurvy?

A
  • Triggered by lack of Ascorbic Acid (Vit C), preventing enzymatic activity of the proline and Lysyl hydroxylase= collagen is not stabilised
39
Q

What are the main symptoms of scurvy?

A

Loss of teeth, gums bleeding, easy bruising

40
Q

What are the symptoms of scurvy caused by?

A

Lack of collagen to repair the wear & tear caused by everyday activities
Known risk factors & remedies for centuries yet scurvy numbers doubled in UK in past 10 years. Around 200 cases in 2022 due to malnourishment

41
Q

What is Menkes disease?

A

-Copper deficiency
-Without treatment, life expectancy= around 3 years
-Rare & X-linked
- Due to mutation in copper transporter

42
Q

What is Ehlers- Danlos?

A

Inherited disorder resulting from poorly formed/ weak collagen in connective tissue (ligaments, tendons, blood vessels, internal organs)

43
Q

What are 7 symptoms of Ehlers- Danlos?

A
  • Joint hypermobility/ dislocations
  • Extreme fatigue
  • Stretchy skin
  • Digestive problems
  • Organ prolapase/ hernias
  • Postural hypotension (POTS)
  • Fragile blood vessels
44
Q

How many gene mutations have been found to cause Ehlers- Danlos?

A
  • 20
  • Many of which make collagen
  • Other genes, e.g. ADAMTS2 and FKBP14 provide instructions for making proteins that process, fold and interact with collagen

IMS- Strand 2 (4 decks)

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