Lecture 9 - Fibrillar proteins (extracellular matrix

Question 1

In order to remodel the matrix, the cells secrete these things that degrade the matrix proteins called what?

Answer 1

Matrix metalloproteinases (MMPs, Zn2+)

Question 2

The activity Metalloproteinases (MMPs) is controlled by specific inhibitors called?

Answer 2

Tissue Inhibitors of MetalloProteinases (TIMPs)

Question 3

These very frequently secrete large amounts of matrix

metalloproteinases (MMPs) to invade the surrounding tissue.

Answer 3

Cancer cells

Question 4

Synthesis of procollagen chains occurs where?

Answer 4

Rough endoplasmic reticulum

Question 5

The triple helix forms where?

Answer 5

Rough endoplasmic reticulum

Question 6

The triple helix is stabilized by what?

Answer 6

Hydroxyproline and hydrogen bonds

Question 7

Hydroxyproline is produced by what enzyme?

Answer 7

Prolyl hydroxylase.

Question 8

Prolyl hydroxylase requires what cofactors ?

Answer 8

Fe2+ and Vitamin C (ascorbate)

Question 9

Crosslinking of collagen chains is helped by what?

Answer 9

Hydroxylysine

Question 10

Hydroxylysine is produced by what enzyme?

Answer 10

Lysyl hydroxylase

Question 11

Lysyl hydroxylase requires what cofactors?

Answer 11

Fe2+ and Vitamin C (ascorbate)

Question 12

The covalent crosslinks within collagen fibers are created through the formation of what?

Answer 12

Oxidized lysine and hydroxylysine residues

Question 13

Oxidization of lysine and hydroxylysine is catalyzed by what enzyme?

Answer 13

Lysyl oxidase.

Question 14

Lysyl oxidase requires what cofactor?

Answer 14

Cu2+

Question 15

Collagen type?

skin, bone, tendon, blood vessels, cornea

Answer 15

Type 1

Question 16

Collagen type?

cartilage, intervertebral disk, virteous body

Answer 16

Type 2

Question 17

Collagen type?

Blood vessels, fetal skin

Answer 17

Type 3

Question 18

Collagen type?

Basement membrane

Answer 18

Type 4

Question 19

• Caused by lack of fruits and vegetables in the diet.
• Prolyl and lysyl hydroxylases are not efficient (require Vitamin C).
• The collagen triple helix is less stabile and crosslinking is also reduced.
• General connective tissue disease.

Answer 19

Vitamin C deficiency

Scurvy

Question 20

Symptoms of what disease?

• Bruises on skin (especially on legs)
• Bleeding gums, loose teeth
• Delayed wound healing
• Bone and joint abnormalities (especially in infants)

Answer 20

Vitamin C deficiency

Scurvy

Question 21

-Disease associated with Type I collagen mutations.
by either reduced number of collagen fibrils, or by defective collagen fibrils.
-Severity can range from perinatal lethal to mild predisposition to fractures

Answer 21

Osteogenesis Imperfecta (OI)

Question 22

Symptoms of what disease?

• Increased incidence of fractures
• Short stature
• Grey or brown teeth that wear down easily (dentinogenesis imperfecta)
• Blue sclera

Answer 22

Osteogenesis Imperfecta (OI)

Question 23

Disease mainly associated with hyperextensive skin, delayed wound healing, etc. Has various forms

Answer 23

Ehlers-Danlos syndrome (EDS)

Question 24

Form of Ehlers-Danlos syndrome (EDS)
-mutations in type V collagen (a fibril associated collagen)
Symptoms:
-hyperextensive skin
-delayed wound healing, atrophic scars
-joint hypermobility

Answer 24

Classic type

Question 25

Form of Ehlers-Danlos syndrome (EDS)
-mutations in type III collagen
Symptoms:
-arterial, intestinal and uterine (during pregnancy) ruptures

Answer 25

Vascular type

Question 26

Form of Ehlers-Danlos syndrome (EDS)
-mutations in lysyl hydroxylase
Symptoms:
-hyperextensive skin
-delayed wound healing, easy bruising, thin scars
-joint hypermobility
-progressive scoliosis (abnormal curving of the spine)
-increased risk of vascular rupture

Answer 26

Kyphoscoliotic type

Question 27

Disease caused by mutations in the Type IV collagen genes

-Affects glomerular basement membranes and can lead to renal failure.

Answer 27

Alport syndrome

Question 28

Symptoms of what disease?

• Hematuria (appearance of red blood cells in urine)
• Proteinuria (increased protein in urine)
• Renal insufficiency
• Sensorineural hearing loss (mutation affects the basement membrane of the organ of Corti in the cochlea of the inner ear)

Answer 28

Alport syndrome

Question 29

Disease where the lung will have lower elastin content, which can lead to the collapse of the small airways (alveoli) when the patient exhales, and leads to emphysema (manifests as shortness of breath).

Answer 29

α1-antitrypsin deficiency

Question 30

What causes α1-antitrypsin deficiency

Answer 30

In the lung, elastin can be degraded by neutrophil elastase (a proteolytic enzyme). α1-antitrypsin, a natural inhibitor of this enzyme, is responsible for preventing excessive degradation of elastin. Deficiency would lead to too much neutrophil elastase = not enough elastin.
Condition is made worse by smokers.

Question 31

Disease caused by mutations in fibrillin-1

Answer 31

Marfan syndrome

Question 32

Symptoms are of what disease?
Very tall stature, kyphoscoliosis
Disproportionally long limbs, fingers and toes
Hyperflexible joints.

Dilation of the aorta
Heart valve problems

Disclocation of the lens of the eyes (ectopia lentis).

Answer 32

Marfan syndrome

Question 33

The main receptors that anchor the cells to the extracellular matrix are

Answer 33

Integrins

Question 34

These interactions are essential for the correct formation of basement membranes.

Answer 34

Integrin-laminin

Question 35

Basement membrane proteins (characteristic cross-shape).

Answer 35

Laminins

Question 36

Disease caused by mutations in certain laminins and integrins.

• Laminin and integrin deficiency
• Mainly affects the basement membrane below the epidermis and mucosal membranes.
• Main symptom is fragile skin that shows extreme blistering.

Epidermis separates from dermis

Answer 36

Junctional epidermolysis bullosa