Collagen and Connective Tissue Diseases L 61

Question 1

What are the characteristics of Collagen and Elastin?

Answer 1

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

Question 2

What is the st of Collagen?

Answer 2

triple helix organized in fibrils
helix seq: Gly-X-Y
X: lysine or proline
Y: Hydroxylysine or Hydroxyproline

Question 3

Is collagen coded by 1 defined gene?

Answer 3

No there is over 30 types of collagen and the genes for it are different and located all over the chromosomes

Question 4

Why is collagen so important?

Answer 4

It is the most abundant protein in the body

25-30% of all proteins

Question 5

Where can we find collagen?

Answer 5

Bone
Teeth
Cartilage
Extracellular Matrix
fetal Skin
Basal Mb
Blood Vessel
Tendons
Conea ....

Question 6

Why is the sequence of collagen important to maintain?

Answer 6

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

Question 7

How is collagen made and matured?

Answer 7

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

Question 8

How are the Proline and Lysine residues hydroxylated?
What is the enzyme?
What are the cofactors?

Answer 8

Lysyl hydroxylaze or prolyl hydroxylase

cofactors are Fe2+ and Vit C = ascorbate

Question 9

What happens if there is a deficiency in Fe2+ or Vit C?

Answer 9

The hydrolyses cannot work well and hence the st of the collagen will be impaired –> problems

Question 10

How are the fibrils of collagen organized?

Answer 10

Into staggered fibrils!

Question 11

How are the collagen molecules staggered/ cross linked?

Answer 11

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

Question 12

What enzyme will be affected in copper deficiency?

Answer 12

Lysyl Oxidases and that is important for

1) Collagen fixation to form cross links
2) Elastin st to form a desmosine cross-link

Question 13

What happens in Vit C deficiency?

Answer 13

Scruvy!
Lys / Pro Hydroxylases cannot work
Symptoms: dermatitise
bruised skin
no healing wounds
pale skin
sunken eyes
loose teeth
corkscrew hair

Question 14

How is scurvy treated?

Answer 14

Give puts Vit C easily reversible and quick cure

Question 15

What is the genetic disease of collagen?

Answer 15

Osteogenesis Imperfecta

Ehlers-Danlos Syndrome

Question 16

What are the different Types of OI and how is their severity ranked?

Answer 16

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

Question 17

What happens in OI II

Answer 17

They die before birth bc of excessive bruising

Question 18

What is another name for OI?

Answer 18

Brittle Bone Disease

Question 19

Which types of Collagen in impaired in all OI?

Answer 19

Type I

Question 20

Which type is the most prevalent in OI?

Answer 20

Type I

Question 21

Which type OI has a correct sequence of collagen I?

Answer 21

Type I

Question 22

What are symptoms of OI?

Answer 22

Short stature
easily broken bones
Hair Loss
Poor teeth development
scoliosis
kyphosis
blue sclera

Question 23

What is Ehlers Danlos?

Answer 23

This is a collection of many different syndromes
Locus Heterogeneity
Mainly AD except Type VI and VIIc

Question 24

What is the most severe EDS?

Answer 24

Type Iv bc it affects blood vessels
AD
Rupture of main arteries and uterus
Can cause death 
Gene: COL3A1

Question 25

What are common symptoms in EDS?

Answer 25

1) Strechy Skin
2) Join hyper mobility
maybe bruising and scoliosis

Question 26

What is elastin?

Answer 26

Rubbery connective Tissue Protein

Question 27

How is elastin different than collagen?

Answer 27

1) It is encoded by 1 gene only
2) It does not have Hydroxylysine
Only Hydroxyproline –> Cannot be glycosidaded

Question 28

How is elastin similar to collagen?

Answer 28

It contains Gly, Pro, Lys, OHPro

Excreted into extracellular matrix

Question 29

What are the characteristics of elastin?

Answer 29

1) It can stretch to multiple times its length
2) It interacts w/ fibrilin
3) It is made from a precursor: proelastin

Question 30

Where can elastin be found?

Answer 30

Walls of arteries
Lungs
Elastic Ligaments
Hair

Question 31

What are diseases related to function of elastin?

Answer 31

Marfaran Syndrome
Mutation is Fibrillin
AD
Gene FBN1 on Chr 15
Lincoln might have had it
Elastin has no support and hence the tissues have no structural support and hence this causes a problem like rupture in the arteries wall

Question 32

What are symptoms of Warfaran?

Answer 32

Tall 
Long limbs
Long fingers= arachnodactyly
Pectus Exavacum- whole in the chest
Many organs can be affected: lungs, arteries, heart, skeleton, eyes

Question 33

Why does elastin has its elasticity?

Answer 33

Bc od desmosine ring
Lysyl Oxidase (same as for cross link in collagen) makes the ring and that is 3 Allysyl + 1 Normal Lysyl residue

-> Collagen can stretch everywhere is all directions