Lecture 23

Question 1

What gives our bodily structures tensile strength?

Answer 1

collagen

Question 2

What gives our bodily structures contractibility?

Answer 2

elastin

Question 3

What is the most abundant protein in the body?

Answer 3

Collagen (25-30%)

Question 4

What are the three types of collagen?

Answer 4

1) fibrin-forming
2) network-forming
3) fibril-associating

Question 5

What genes make up fibrin forming collagen?

Answer 5

col1A1 and col1A2

Question 6

What is the structure of collagen and what makes this structure possible?

Answer 6

• Triple helical

- the amino acid sequence glyXY (Glycine followed by two other amino acids)

Question 7

Why is Glycine used in collagen and what are the two amino acids that usually follow it?

Answer 7

• Glycine has the smallest side chain which allows for it be tightly woven in a triple helical structure
• X is usually proline, and Y is usually hydroxyproline or hydroxylysine

Question 8

How many different collagen genes are there in the genome?

Answer 8

42

Question 9

How is Collagen assembled?

Answer 9

• mRNA is translated into protein in the cytoplasm where it then chooses a proline and lysine to be hydroxylated by enzymes and modified with carbohydrates.
• three collagen chains then begin to self assemble starting from the C end to the N end.

Question 10

What occurs at the C and N end of nascent collagen that doesn’t occur anywhere else in the collagen?

Answer 10

Disulfide bonds that help with folding

Question 11

In what way are collagen molecules arranged?

Answer 11

Staggered for strength

Question 12

What cells make collagen for cartilage?

Answer 12

condricytes

Question 13

What cells make collagen for bone?

Answer 13

osteoblasts

Question 14

What cells make collagen for everything but bone and cartilage?

Answer 14

fibroblasts

Question 15

What enzyme are responsible for the hydroxylation of proline and lysine? And what do these enzymes require?

Answer 15

• prolyl hydroxylase and lysyl hydroxylase.

- they require Fe2+ and vitamin C (ascorbic acid)

Question 16

what enzyme is responsible for the crosslinks in collagen fibers and what is its cofactor?

Answer 16

• lysyloxidase

- copper

Question 17

what is the purpose of crosslinking and how is it accomplished?

Answer 17

• it helps stabilize the triple helix, keeping the staggered collagen molecules in place
• it crosslinks one lysine to another lysine

Question 18

what happens in menkes disease?

Answer 18

it is a copper deficiency that results in lysyloxidase malfunctioning

Question 19

what happens in scurvy disease and why?

Answer 19

• discoloration of skin, malfunctioning blood vessels, loss of teeth, sunken eyes.
• a deficiency of Vitamin C prevents collagen’s proline and lysine from being hydroxylated by their respective enzymes (cofactor)
• completely reversible

Question 20

who was the doctor who held the first clinical trial?

Answer 20

Dr. James Lind in 1747

Question 21

what is osteogenesis imperfecta (OI)

Answer 21

• brittle bone disease due to collagen gene mutation.

Question 22

what is the order of severity among the forms of Osteogenesis imperfecta?

Answer 22

type 2 is the worst
type 3 and 4 are pretty bad
type 1 is mild as hell.

Question 23

what is the usual cause of type 2, 3, and 4 OI?

Answer 23

substitutions that change glycine to a larger amino acid in col1A1 and col1A2

Question 24

what is the usual reason for type I OI?

Answer 24

a premature stop codon that inhibits translation of a full protein

Question 25

what is the cause of the most severe form of Ehlers-Danlos syndrome (EDS) and what type of EDS is this?

Answer 25

defects in the col3A1

- type 4 or “vascular”

Question 26

where is elastin found?

Answer 26

• walls of arteries, lungs, and ligaments.

Question 27

what protein must elastin interact with for it to have many of its characteristics?

Answer 27

fibrillin

Question 28

what is the gene for fibrillin and what occurs when there is a mutation in it?

Answer 28

• FBN1 on chromosome 15 (same chromosome as PWS and AS)

- results in Marfan syndrome which can lead to ruptures in the walls of arteries such as the aorta.

Question 29

what are the characteristics of Marfan Syndrome?

Answer 29

long legs
long fingers
long limbs
long…

Question 30

what allows elastin to be so stretchy?

Answer 30

4 way crosslinked lysines called desmosine crosslinks.