Lecture 23 Flashcards
What gives our bodily structures tensile strength?
collagen
What gives our bodily structures contractibility?
elastin
What is the most abundant protein in the body?
Collagen (25-30%)
What are the three types of collagen?
1) fibrin-forming
2) network-forming
3) fibril-associating
What genes make up fibrin forming collagen?
col1A1 and col1A2
What is the structure of collagen and what makes this structure possible?
- Triple helical
- the amino acid sequence glyXY (Glycine followed by two other amino acids)
Why is Glycine used in collagen and what are the two amino acids that usually follow it?
- 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
How many different collagen genes are there in the genome?
42
How is Collagen assembled?
- 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.
What occurs at the C and N end of nascent collagen that doesn’t occur anywhere else in the collagen?
Disulfide bonds that help with folding
In what way are collagen molecules arranged?
Staggered for strength
What cells make collagen for cartilage?
condricytes
What cells make collagen for bone?
osteoblasts
What cells make collagen for everything but bone and cartilage?
fibroblasts
What enzyme are responsible for the hydroxylation of proline and lysine? And what do these enzymes require?
- prolyl hydroxylase and lysyl hydroxylase.
- they require Fe2+ and vitamin C (ascorbic acid)
what enzyme is responsible for the crosslinks in collagen fibers and what is its cofactor?
- lysyloxidase
- copper
what is the purpose of crosslinking and how is it accomplished?
- it helps stabilize the triple helix, keeping the staggered collagen molecules in place
- it crosslinks one lysine to another lysine
what happens in menkes disease?
it is a copper deficiency that results in lysyloxidase malfunctioning
what happens in scurvy disease and why?
- 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
who was the doctor who held the first clinical trial?
Dr. James Lind in 1747
what is osteogenesis imperfecta (OI)
- brittle bone disease due to collagen gene mutation.
what is the order of severity among the forms of Osteogenesis imperfecta?
type 2 is the worst
type 3 and 4 are pretty bad
type 1 is mild as hell.
what is the usual cause of type 2, 3, and 4 OI?
substitutions that change glycine to a larger amino acid in col1A1 and col1A2
what is the usual reason for type I OI?
a premature stop codon that inhibits translation of a full protein
what is the cause of the most severe form of Ehlers-Danlos syndrome (EDS) and what type of EDS is this?
defects in the col3A1
- type 4 or “vascular”
where is elastin found?
- walls of arteries, lungs, and ligaments.
what protein must elastin interact with for it to have many of its characteristics?
fibrillin
what is the gene for fibrillin and what occurs when there is a mutation in it?
- 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.
what are the characteristics of Marfan Syndrome?
long legs
long fingers
long limbs
long…
what allows elastin to be so stretchy?
4 way crosslinked lysines called desmosine crosslinks.
