Collagen and Connective Tissue Diseases L 61 Flashcards
What are the characteristics of Collagen and Elastin?
1) They are main component of the connective tissue
2) Structural proteins
3) Long half-life
4) Insoluble
5) Stable
6) Collagen=tensile strength Elastin= contractibility
What is the st of Collagen?
triple helix organized in fibrils
helix seq: Gly-X-Y
X: lysine or proline
Y: Hydroxylysine or Hydroxyproline
Is collagen coded by 1 defined gene?
No there is over 30 types of collagen and the genes for it are different and located all over the chromosomes
Why is collagen so important?
It is the most abundant protein in the body
25-30% of all proteins
Where can we find collagen?
Bone Teeth Cartilage Extracellular Matrix fetal Skin Basal Mb Blood Vessel Tendons Conea ....
Why is the sequence of collagen important to maintain?
Bc since glycine is the smaller aa, it is cruicial to maintain the triple helix st
If substituted, that would be a problem since the aa will be bulkier
–> OI
How is collagen made and matured?
1) mRNA
2) Protein
3) Protein goes to ER
4) Certain Lys or Pro are hydroxylated
5) Certain Hydroxylated Lys NOT Pro are glycosilated (glucose or galactose)
6) The pro-alpha chain assemble and the C terminal form disulfide bonds
7) the chains zip in a zip-like manner
8) Protein ejected into the extracellular matrix
9) N and C terminal, which are not in triple helix get cut off
- -> mature collagen
10) mature collagen assemble into cross-linked fibrils to maintain tensile strength
How are the Proline and Lysine residues hydroxylated?
What is the enzyme?
What are the cofactors?
Lysyl hydroxylaze or prolyl hydroxylase
cofactors are Fe2+ and Vit C = ascorbate
What happens if there is a deficiency in Fe2+ or Vit C?
The hydrolyses cannot work well and hence the st of the collagen will be impaired –> problems
How are the fibrils of collagen organized?
Into staggered fibrils!
How are the collagen molecules staggered/ cross linked?
This happens bc of the interactions of 2 lysine residues between the helices of the same collagen molecules and different collagen molecule as well as different fibrils
Lysine —> Allysine E= LYSYL OXIDASE using COPPER
Allysine and Lysine interact to form a linear chain
What enzyme will be affected in copper deficiency?
Lysyl Oxidases and that is important for
1) Collagen fixation to form cross links
2) Elastin st to form a desmosine cross-link
What happens in Vit C deficiency?
Scruvy! Lys / Pro Hydroxylases cannot work Symptoms: dermatitise bruised skin no healing wounds pale skin sunken eyes loose teeth corkscrew hair
How is scurvy treated?
Give puts Vit C easily reversible and quick cure
What is the genetic disease of collagen?
Osteogenesis Imperfecta
Ehlers-Danlos Syndrome
What are the different Types of OI and how is their severity ranked?
2>3>4>1
2, 3, 4 : Gly substituted for another aa in COL1A1 or COL1A2
1: Early termination site or changed splice site and that causes less Collagen to be made
What happens in OI II
They die before birth bc of excessive bruising
What is another name for OI?
Brittle Bone Disease
Which types of Collagen in impaired in all OI?
Type I
Which type is the most prevalent in OI?
Type I
Which type OI has a correct sequence of collagen I?
Type I
What are symptoms of OI?
Short stature easily broken bones Hair Loss Poor teeth development scoliosis kyphosis blue sclera
What is Ehlers Danlos?
This is a collection of many different syndromes
Locus Heterogeneity
Mainly AD except Type VI and VIIc
What is the most severe EDS?
Type Iv bc it affects blood vessels AD Rupture of main arteries and uterus Can cause death Gene: COL3A1
