Collagen Flashcards

1
Q

What tri-peptide is found as a regular repeat in fibril-forming collagens?

A

Gly-X-Y

X=proline

Y=hydroxyproline

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2
Q

Why does hydroxylation of proline stabilize the collagen helix?

A

Hydroxylation of proline fixes the side chain in the exo conformation, whicih is preferred for proline sidechains in the Y position –> increases collagen’s thermal stability & prevents unwinding

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3
Q

Why does collagen have such high tensile strength?

A

Multiple interchain hydrogen bonds and dense packing of the triple helix

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4
Q

Mutation of what residue in collagen would be most likely to cause disease and why?

A

Glycine

Any sidechain other than the hydrogen of Gly would disrupt packing in the collagen triple helix

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5
Q

Post translational modifications of collagen that occur inside the cell

A

Hydroxylation of Pro & Lys

Glycosylation of hydroxylysine

Disulfide bond formation at C-terminal propeptide extension

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6
Q

Why is vitamin C required for proper collagen fibril formation?

A

It’s required for prolyl and lysyl hydroxylation, which stabilizes the triple helix

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7
Q

What post-translational modifications of collagen occur after the molecule has been secreted?

A

Peptidases clip off N- and C-terminal extensions from the procollagen

Lysyl oxidation

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8
Q

Why do some modifications occur inside the cell and some outside?

A

Prevents the tropocollagen molecule from self-assembling inside the cell

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9
Q

Ehlers-Danlos syndrome

A

Deficiency in procollagen peptidase

–> carboxyl- and amino-terminal ends of procollagen aren’t cleaved into tropocollagen in the ECM, so fibrils don’t form

–> loose joints

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10
Q

Menke’s syndrome

A

Defect in copper (Cu) absorption or metabolism–> kinky, steel-colored hair, growth retardation, neural issues

Lysyl oxidase requires Cu2+ as a cofactor to crosslink collagen fibrils

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11
Q

Major collagen type in bones

A

Type I

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12
Q

Major collagen type in basement membranes

A

type IV

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13
Q

Why do disorders in type IV collagen cause hereditary nephritis?

A

Type IV collagen is the major scaffold protein of the basement membrane.

The double basement membrane in the glomerulus is responsible for keeping proteins in the plasma from spilling into the urine during glomerular filtration.

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14
Q

Increased degradation of elastin in the lung causes

A

emphysema

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15
Q

Fibrillin

A

Glycoprotein that coats elastin fibers

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16
Q

Marfan’s syndrome is a genetic disease that involves mutations in

A

The fibrillin gene

17
Q

Elastin- what composition gives it its characteristic properties?

A

Highly hydrophobic protein rich in Gly and Pro; repeating peptapeptide Val-Pro-Gly-Val-Gly

Unique cross-links (desmosine & isodesmosine) allow it return to its original conformation

18
Q

Secondary structure of elastin

A

Random coil that can stretch and relax

19
Q

Elastic fibrisl are covered with

A

Microfibrils composed primarily of the glycoprotein fibrillin

20
Q

a1-Antitrypsin

A

Produced primarily in the liver

Prevents elastin degradation by inhibiting elastase

21
Q

A deficiency of a1-AT can cause

A

Emphysema and cirrhosis of the liver

(cigarette smoek can also stimulate elastase to lvls that can’ tbe controlled by a1-AT)

22
Q

Big differences between Marfan’s and Homocystinuria

A
23
Q

Fragile bones that break easily, triangular-shaped face, blue sclera, hearing loss, scoliosis, thin, smooth skin, loose joints, low muscle tone, brittle teeth

A

Type I Osteogenesis Imperfecta - AD mutation that reduces type I collagen by 50%

24
Q

Type II OI

A

Type II is more severe, resulting in death during embryogenesis or by bone fracturing during birthing; results from a change in the modifications that occur to collagen during synthesis

25
Q
A
26
Q

Treatment of osteogenesis imperfecta

A

Bisphosphonates inactivates/causes apoptosis of osteoclasts (breaks down bone tissue) and decreases apoptosis among osteoblasts (lays down new bone)

27
Q

Tropocollagen

A

The triple helix of type I collagen

28
Q

Tendon vs skin

Collagen & elastin content

A

Tendon needs to be strong -> collagen

Skin needs to stretch -> elastin

29
Q

Scurvy

A

Deficiency of vitamin C

–> proline-4-hydroxylase can’t convert Pro to 4-hydroxypro for the Y position in collagen

–> unstable collagen

–> weakness, spongy/bleeding gums, poor wound healing, follicular hyperkeratosis, perifollicular hemorrhage

30
Q

Fibril collagens

A

Types 1, 2, 3, 5, 11

Characteristic tropocollagen tripl ehelix that forms staggered fibrils –> striation

31
Q

Collagen synthesis

A
  1. Translation on RER into preprocollagen
  2. Translocation into the ER while proline 4-hydroxylase generates 4-hydroxyprolines at the Y position
  3. Cleave off signal sequence & form a triple helix in the cytosol into procollagen
    1. ​Disulfide bonds between carboxyl-terminal ends
  4. Secretion out into the ECM, where procollagen peptidases cleave the carboxyl-terminal and amino-termianl ends into collagen
32
Q

Fibril-associated collagens

A

Interrupted triple helcies with globular heads on them

33
Q

Sheet/network-like collagen

A

type 4 inthe basement membranes and basal lamina

34
Q

Anchoring fibrils

A

type 7

Supports or connects dermal and epidermal layers

35
Q

Alport’s syndrome

A

Disorders of basement membranes of kidney, cochlea, and eye due to mutations in type 4 collagen in basement membranes & basal lamina.

–> proteinuria, HTN, end-stage renal disease, hearing loss

X-linked or AD, depending on which type IV collagen gene is involved