Lec 5 - Extracellular Matrix

Question 1

How does scuvy clinically present

Answer 1

• Missing teeth
• bruises
• coilly hairs
• poor wound healing
• bleeding gums
• easliy bruised skin

missing vitamin c / asorbic acid

Question 2

How does OI clinically present

Answer 2

collagen gene mutation, spontaneous
mutation in type 1 collagen
In type II, III and IV OI- subsitution in gene for COL1A1 or COL1A2 Gly for another AA w/ bluky side chain - prevents proper folding

• brittle bones
• short stature
• bowed legs
• scoliosis
• cythosis
• abnormal hearing
• blue scallera
• type II, III and IV not viable

Question 3

Types of collagen vs types of OI

Answer 3

12 different types of collagen
All OI comes from error in type 1 collagen
4 different types of OI
most sever II, least sever I

Question 4

Types of EDS and symptoms

Answer 4

Collection of different kinds of genetic defects

skin and joint hyper mob , bruises
joint hypermobility, pain
vascular - arterial or uterine rupture
scoliosis
fragile skin, bruising

*copy chart in

Question 5

Marfan syndrom is a defect in ____ related to ____

Clinical presentation includes

Answer 5

Fibrillin related to elastin

AD, FBN1 gene on chromosome 15 - encodes for fibrilin, esse

w/o fibrilin long arms, arachnodactyly - Long fingers, pectus excavatum - sunken chest, dilation of aorta

Question 6

How is collagen made and assembled

Answer 6

Genes transcripted and mRNA is translated in cytosol where selected proline and lysine residues are hydroxylated (prolyl and lysyl hydroxylase - required Fe2++ and vit c as co-factors)
then
selected hydroxylysine residues are glycosylated with glucose and galatose

Then still in cytoplasm - three pro-a chains assembled from c’ end. held togethre with di-sulfides bonds intra and inter chain at c terminal

Zipper like folding

pro-collagen (with n and c temrinals) secreated from a golgi vacuole into ECM

N and C terminal are cleaved by procollagen peptidases

Individual collagen tripple helixs assemble into fibrils - stablized by crosslining (lysyl oxidases - need copper as co-factor)

Question 7

Post translational modificatoins of collagen

Question 8

Cross linking of collagen

Answer 8

Make stable fibrils
done by lysyl oxidase
need copper as co factor
associated diseases:
- menkes diease - copper transport deficeny disease - decreased lysyl oxidase activity - tissue fragility
- wilkonsons diease - copper overlaod disease - tissue rigidity

Question 9

There are ____ collagen genes throughout genome

Answer 9

many! not just on one chromosome

Question 10

Strucutre of collagen. all collagens are ____helical

Answer 10

triple-helical
have AA strucutre Gly-X-Y (gly is small!)
X is proline
Y is hydroxly-proline of hydroxyl-lysine - BIG side groups

Question 11

Dentiogenesis imperfecta

Question 12

Type 1 OI mutation

Answer 12

mutation in type 1 collagen
Splice or pre-termination mutation
mRNA degrated before translated into protien - less of it but what makes it is fine

Question 13

Mutations in ____ are responsible for _____

Answer 13

fibrilin
marfan syndrome

Question 14

elastine is a [________] found in [_____]

Answer 14

rubbery connective tissue protien
found in walls of ateries, lungs and elastic ligaments

Question 15

Elastin is a [_____] and sythesized from [_____]

Answer 15

insoluble protien polymer synthesized from Tropoelastin
one genetic type

Question 16

Elastin is rich in [ ] and does not have [ ]

Answer 16

Glycine
proline
lysine

only a little hydroxyproline

no hydroxylsine

interacts with fibrilin