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Flashcards in ECM Deck (31):
1

What are the 3 major AA types in collagen?

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

*Pro and Lys are very often hydroxylated

2

What is a very common AA sequence?

Gly-X-Y

X is usually Pro
Y is usually hydroxyPro

3

What is the secondary/tertiary structure of collagen?

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

4

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

R handed triple helix

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

5

What causes osteogenesis imperfecta?

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

6

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

N-terminal extension and C-terminal extension

7

Where does hydroxylation of proline and lysine occur?

ER

8

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

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

9

What disease occurs when ascorbate is missing from the diet?

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

10

Why is hydroxylation important?

It is required for cross-linking of collagen molecules.

11

How is lysine hydroxylated? Does it require a cofactor?

Lysyl hydroxylase. Yes, also requires ascorbate

12

Which common collagen AA can also be glycosylated?

(Hydroxy)Lysine

13

How does hydroxyproline affect Tm?

Increases it

14

How is pro-collagen converted into tropocollagen and where?

N and C terminal peptidases in the extracellular space.

15

What creates the striated appearance of collagen?

asymmetric 1/4 stagger

16

How are collagen fibers stabilized?

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

What causes the disease lathyrism?

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

18

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

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

19

Which AAs make up elastin?

1. Proline
2. Glycine
3. Valine

20

Describe elastin's structure/properties.

No regular secondary structure

Hydrophobic/highly insoluble

21

Describe the "maturation" of elastin fibers.

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

22

What enzyme mediated elastin turnover and how quick is it?

Elastase - On the order of years

23

What causes emphysema?

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

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

LOX (lysyl oxidase)

25

What are aggrecan and decorin?

Proteoglycans

26

What is hyaluronan?

GAG

27

What are chondroitin sulfate and keratan sulfate?

GAGs

28

What stabilizes and directs helical formation of procollagen?

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

29

Which step of collagen formation requires iron + molecular oxygen?

Hydroxylation

30

Which step of collagen formation requires copper + molecular oxygen?

Crosslinking (lysyl oxidase)

31

What is the most common problem that causes Ehlers Danlos?

Crosslinking of collagen