Collagen Flashcards

(52 cards)

1
Q

T or F: collagen is an integral membrane protein.

A

False, it is located completely outside of cells

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2
Q

What sequence is common to all types of collagen?

A

Gly-X-Y sequence

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3
Q

What type of proteins degrade collagen?

A

Metalloproteinases

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4
Q

What is primary structural element of connective tissue?

A

Collagen

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5
Q

T or F: collagen undergoes minimal amounts of post translational processing

A

False, Collagen is highly post translationally processed

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6
Q

Type I collagen

  • Form
  • Where
A

Form:
Fibrillar (fiber form)

Where:
Bone, Skin, Tendon, Cornea, Many others

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7
Q

Type II collagen

  • Form
  • Where
A

Form:
Fibrillar

Where:
Cartilage, Vitreous of eye

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8
Q

Type III

  • Form
  • Where
A

Form:

Skin, Blood vessels, many other

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9
Q

Type IV

  • Form
  • Where
A

Form:
Network

Where:
Basal Lamina Sheets

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10
Q

Type V

  • Form
  • Where
A

Form:
Fibrillar

Where:
Bone, Skin, Tendon, Cornea, Many others

***Note: this is the same as type I

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11
Q

Type VIII

  • Form
  • Where
A

Form:
Network

Where:
Endothelial Lining, cornea

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12
Q

What features are common to all collagen regardless of tissue type?

  • structure
  • sequence
  • Post-Translational Modifications
A

Structure:
- 3 domains wound around each other into a triple helix

Sequence:
- Each subunit contains a Gly-X-Y repeating sequence

PTMs:
- Hydroxylation of proline and lysine

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13
Q

T or F: a single collagen fibril contains many collagen strands

A

True

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14
Q

End to end aggregation of small fibrils form longer fibrils that aggregate to form ____________.

A

Fibers, collagen fibers self assemble from collagen subunits

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15
Q

T or F: different forms of collagen are genetically distinct

A

True, many different collagen genes encode for different types

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16
Q

What proteins commonly fill the x, y positions in Gly-X-Y.

A
  • Hydroxyproline (HYP, and PRO)
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17
Q

Why is glycine nesessary at every 3rd amino acid in collagen?

A
  • is H for an R group is the only thing small enough to fit in the triple helix
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18
Q

What is the result of changing gly to cys in the collagen sequence Gly-X-Y?
- Resultant disease

A
  • Cysteine has a larger side chain and puts a bulge in the collagen
  • This weakens the collagen
  • Osteogenesis imperfecta results (aka brittle bone disease)

**Normally this is a small defect but in collagen this glycine is vital

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19
Q

What it is needed for production of hydroxyproline and hydroxylysine needed for collagen formation?
- what does a deficiency result in?

A
  • Vitamin C

- Vitamin C deficiency leads to scurvy

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20
Q

What enzyme is uses vitamin C as a cofactor?

A
  • Prolyl Hydroxylase enzyme
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21
Q

What are the substrates and products of prolyl hydroxylase?

- Coefactors

A

Substrates:
Proline + alpha KG + O2

Products:
Hydroxyproline + Succinate + CO2

Cofactor:
VITAMIN C

22
Q

Lysyl Hydroxylase

  • Reaction
  • Substrates
  • Products
  • Coefactors
A
  • make hydroxylysine

Substrate:
Lysine

Product:
Hydroxylysine

Cofactor:
Vitamin C

23
Q

What addition can be made to hydroxylysine?

***this is important

A

It can be O-glycosylate for collagen specific glycosylation

24
Q

Slow wound healing and bleeding of gums and lips are symptoms of what disease related to collagen?

A
  • Scurvy, resulting from Vitamin C deficiency

- Scurvy results from lack of Hyroxyproline and Hydroxylysine

25
T or F: hydroxyproline and hydroxylysine are essential to collagen formation
True, scruvy is the result of not having these residues
26
Why would you measure someone's urine hydroxyproline levels?
- It tells you about bone turnover ***note: hydroxyproline is peed out because it is post-translationally modified and can't be reused
27
What would you expect urine hydroxyproline levels to be like in a patient that has scruvy.
Levels will likely be LOW because they lack the appropriate enzymes to make it
28
Why shouldn't you eat jellow before a hydroxyproline urine test?
**Don't eat jello before one of these tests because it contains collagen and will artificially raise your hydroxyproline levels
29
7 steps of collagen synth.
1. Synthesis of Pro-alpha chain 2. Hydroxylation of Selected Prolines and lysines 3. Glycosylation of selected hydroxylysines 4. Self-Assembly of 3 pro-alpha chains 5. Procollagen Triple Helix Formation 6. Secretion 7. Cleavage of Pro-Peptides
30
Why does lack of hydroxylation causes the effects seen in scurvy?
- Collagen is destabilized and has a lower melting temperature - Once dissociated the chains are simply degraded
31
What differentiates Procollagen from collagen? | - what is the importance of this difference?
Procollagen: - Contains GLOBULAR portions Purpose of Globular parts: - help align the 3 strands into a triple helix
32
T or F: the globular domains must be removed from procollagen to form collagen which can assemble into fibrils and fibers
True
33
What happens if the globular domains are not removed from the procollagen protein?
Dermatosparaxis: - Fragile Skin - Abnormally elastic Skin and Tissues **Skin loss in cattle and sheep
34
Why does presence of globular domains on procollagen cause skin to be brittle?
- Collagen needs its ends to be free so that it can bind to other collagens and form large strands
35
After collagen is assembled what allows for cross linking between strands? - enzyme - residues
1. Lysyl Oxidase (not hydroxylase) form ALDEHYDES of lysine and hydroxylysine 2. Schiff Base is formed
36
Issues in what 3 areas of collagen formation lead to all of the diseases observed?
1. Biosythesis 2. Procollagen processing 3. Crosslinking
37
Where does translation of collagen polypeptides typically occur?
RER
38
What causes Scurvy?
Lack of Vit C, coefactor needed for hydroxylation of proline and lysine
39
What causes Ehlers-Danlos VI?
- Lysyl Hydroxylase Deficiency **so you still have your hydroxyprolines
40
What do you need procollagen domains? | - why is it bad if they are never cleaved?
- Needed for proper alignment | - Must get rid of so that fiber formation can happen
41
Ehlers-Danlos VII - Defect - What part of collagen formation is messed up?
N-propetidase defect - Globular ends (procollgen domains) are not cleaved
42
Ehlers-Danlos IX - Defect - What part of collagen formation is messed up?
- Lysyl Oxidase deficient | - No Allysine formation so Schiff bases and therefore cross-links can't be formed
43
What do lathrogens do? | - effect?
- Inhibit Lysyl Oxidase | - This mimics the effects of Ehlers-Danlos (IX)
44
Metalloproteinases (MMP) - Function - procollagenase - inhibitor
- Break Down Collagen Procollagenase: - activates the MMP Inhibitor: TIMPs
45
What physiologic processes involve metalloproteinases (MMP)?
- Tissue Development - Cancer Metastasis - Wound Healing
46
T or F: globular ends are maintained in Type IV collagen
True, allows it to form a tetramer **Note: Type IV collagen needed to form a scaffold for the basal lamina
47
Besides type IV collagen, what other type maintains its globular domain?
Type IX
48
What is located at the globular end of Type IX collagen? | - what type of collagen is Type IX typically associated with?
a GAG chain - Type II
49
What is the relationship between type II and Type IX collagen?
- Type II fiber size is regulated by type IX collagen ALSO, GAG components of Type IX can interact with other collagens
50
What forms the sievelike structure of basal laminae?
- Networks Formed by Type IV collagen
51
What is the job of fibril associated collagens? | - example?
Coat other collagens to: - Limit Growth of the Fiber - Enhance interaction of fiber with ECM
52
What collagen has the job of anchoring fibril to hold epithelia onto underlying CT?
Type VII