ECM Flashcards

1
Q

What are the 3 major AA types in collagen?

A
  1. Glycine (1/3)
  2. Proline (1/4)
  3. Lysine

*Pro and Lys are very often hydroxylated

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2
Q

What is a very common AA sequence?

A

Gly-X-Y

X is usually Pro
Y is usually hydroxyPro

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3
Q

What is the secondary/tertiary structure of collagen?

A

Type II trans helix (2.8 angstrom rise per AA along the fiber axis).

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4
Q

What is the quaternary structure of collagen? What is it called?

A

R handed triple helix

Each chain (of the 3) is an Alpha chain, called Tropocollagen as a whole

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5
Q

What causes osteogenesis imperfecta?

A

Replacement of glycine with a bulkier AA prevents tight binding of triple helix.

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6
Q

Why are alpha chain-encoding genes so much longer than the final polypeptide?

A

N-terminal extension and C-terminal extension

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7
Q

Where does hydroxylation of proline and lysine occur?

A

ER

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8
Q

How is proline hydroxylated and what is an important co-factor?

A

Prolyl hydroxylase hydroxylates C$ using ascorbate as a co-factor.

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9
Q

What disease occurs when ascorbate is missing from the diet?

A

Scurvy: skin lesions, fragile blood vessels, poor wound healing.

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10
Q

Why is hydroxylation important?

A

It is required for cross-linking of collagen molecules.

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11
Q

How is lysine hydroxylated? Does it require a cofactor?

A

Lysyl hydroxylase. Yes, also requires ascorbate

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12
Q

Which common collagen AA can also be glycosylated?

A

(Hydroxy)Lysine

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13
Q

How does hydroxyproline affect Tm?

A

Increases it

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14
Q

How is pro-collagen converted into tropocollagen and where?

A

N and C terminal peptidases in the extracellular space.

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15
Q

What creates the striated appearance of collagen?

A

asymmetric 1/4 stagger

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16
Q

How are collagen fibers stabilized?

A
  1. Covalent crosslinking of lysine into an aldehyde by lysyl oxidase (LOX)
  2. Formation of hydroxypyridnium ring (pyridinoline) between 2 hydroxyllysyl and 1 lysyl residues
17
Q

What causes the disease lathyrism?

A

Ingestion of BAPN from sweet peas which inhibits LOX, thus destabilizing collagen fibers

18
Q

How does the body degrade collagen for regular turnover and repair?

A

Matrix metalloproteinases (MMPs) cleave the collagen triple helix 75& from the N terminus, lowering the Tm and allowing for denaturation at body temp.

19
Q

Which AAs make up elastin?

A
  1. Proline
  2. Glycine
  3. Valine
20
Q

Describe elastin’s structure/properties.

A

No regular secondary structure

Hydrophobic/highly insoluble

21
Q

Describe the “maturation” of elastin fibers.

A

70kDa monomer called tropoelastin -> secreted to extracellular space -> crosslinking by LOX forming a “desmosine” link (now insoluble fiber)

22
Q

What enzyme mediated elastin turnover and how quick is it?

A

Elastase - On the order of years

23
Q

What causes emphysema?

A

Destruction of the elastin fibers in the alveolar epithelia of the lungs. Destruction of walls results in large air gaps and reduced SA for exchange.

24
Q

What enzyme if defective is involved in Menkes kinky-hair syndrome and Ehlers Danlos, among others?

A

LOX (lysyl oxidase)

25
Q

What are aggrecan and decorin?

A

Proteoglycans

26
Q

What is hyaluronan?

A

GAG

27
Q

What are chondroitin sulfate and keratan sulfate?

A

GAGs

28
Q

What stabilizes and directs helical formation of procollagen?

A

Sulfhydryls/cysteines on the end. These are the ends that get sliced by the peptidases to make the soluble tropocollagen!

29
Q

Which step of collagen formation requires iron + molecular oxygen?

A

Hydroxylation

30
Q

Which step of collagen formation requires copper + molecular oxygen?

A

Crosslinking (lysyl oxidase)

31
Q

What is the most common problem that causes Ehlers Danlos?

A

Crosslinking of collagen