Collagen/Elastin Flashcards
(30 cards)
Tri-peptide repeat in collagen
Gly-X-Y
X = proline Y = hydroxyproline
How does hydroxylation of proline stabilize the collagen helix?
It ‘fixes’ the side chain of the proline into the exo confirmation
This confirmation is preferred in the Y position
This increases the collagen’s thermal stability and keeps it from unwinding and getting degraded
Mutation is which residue will cause a disease state in the triple helix and why?
Glycine…it has a Hydrogen R-group…any other bigger side chain will disrupt the tight packing of the triple helix
This will make the helix susceptible to degradation
Post-translation modifications of collagen…inside the cell
- Hydroxylation of proline and lysine residues in the polypeptide
- Gylcosylation of hydroxylysine residues
- Disulfide bond formation at C-terminal propeptide extension
Vitamin that is needed for proper collagen fibril formation?
Vitamin C
It is a cofactor to the enzyme…
Required for prolyl and lysyl hydroxylation
Post-translation modifications of collagen after molecule has been secreted?
- N & C terminal extensions are clipped from the procollagen molecule…done by peptidases
- Lysyl oxidation
Why are post-translation modifications separated by inside/outside of the cell?
Prevent tropocollagen molecule from self-assembling inside the cell
Diseases from improper post-translation modifications of collagen?
Ehlers-Danlos Syndrome —> deficiency of procollagen peptidases
Menke’s Syndrome —> defect in cupper (Cu2+) absorption or metabolism…which is needed as a cofactor for the enzyme responsible for crosslinking collagen fibrils outside the cell (lysyl oxidase)
Major collagen in bone
Type I
Major collagen in basement membranes?
Type IV
Relation between type IV collagen and hereditary nephritis?
The double basement membrane in the glomerulus is responsible for keeping proteins in the plasma from spilling to the urine during glomerular filtration
Cause of emphysema?
Increased degradation of elastin in the lung
What is fibrillin?
What disease is associated with mutations in the fibrillin gene?
Fibrillin is a glycoprotein that coats elastin fibers
Marfan’s syndrome
Elastin
Highly hydrophobic protein rich in glycine and proline
Repeats of Val-Pro-Gly-Val-Gly
Secondary structure = random coil that can stretch and relax
Desmosine and isodesmosine = the crosslinks that help elastin return to its original conformation
Alpha1 - antitrypsin
Produced in liver
Prevents elastin degradation by inhibiting elastase activity
Deficiency = can cause emphysema and cirrhosis of the liver
Smoking can also stimulate the activity of elastase to levels that cannot be controlled by alpha1-AT
Marfan’s Syndrome
NO osteoporosis
Mental retardation and thrombosis are UNCOMMON
Autosomal dominant
Lens DISLOCATE UP
No approved treatments
Homocystinuria
Frequently have osteoporosis
Mental retardation and thrombosis COMMON
Autosomal recessive
Lens dislocate DOWN
Can be treated with dietary supplements
Osteogenesis imperfecta
Symptoms: fragile bones that fracture easily…blue sclera…triangular faces…loose joints….brittle teeth
Cause: Malfunction in the body’s production of collagen
Type I: most common, blue sclera, and hearing loss, autosomal dominant…normal stature and little to no deformity
Type II: lethal in the perinatal period…structural alterations in both chains of collagen and is autosomal dominant
Bisphosphonates
What are they used to treat?
Used to treat osteogenesis imperfecta
Act by inactivating osteoclasts
Some can also decrease the apoptosis of osteoblasts
Tropocollagen
Type I collagen triple helix
How are the chains of the triple helix are stabilized
Interchain H-Bonds
Proline preferred conformation
Endo-
(Hydroxyproline = exo)
Most thermodynamically stable for both…
Proline-4-hydroxylase
Uses vitamin C as a cofactor
Responsible for post-translation modifications of proline and hydroxyproline
Purpose of the disulfide bond formation in the post-translation modifications of collagen?
Needed to initiate the triple helix formation…brings the strands close together
