1H Foundations 8 - Extracellular environmant

Question 1

What protein is involved in transporting an endocytosed vesicle from the plasma membrane to the endosome?

Answer 1

Clathrin

Question 2

Which metals are known to facilitate the generation of oxygen free radicals?

Answer 2

Iron and copper

Question 3

Which tumor suppressor proteins prevent the progression of the cell into S-phase?

Answer 3

Rb and p53

Question 4

• Most abundant protein in the body
• Extensively modified by posttranslational modification
• Organises and strengthens extracellular matrix

Answer 4

Collagen

Question 5

Most common (90%) type of collagen

Answer 5

Type 1

Question 6

Where can you find type 1 collagen?

Answer 6

In hard things (bONE)

• Bone
• Skin
• Tendon
• Dentin
• Fascia
• Cornea
• Late wound repair

Question 7

Which type of collagen is defective in Osteogenesis imperfecta?

Answer 7

Type 1

Question 8

Where can you type 2 collagen?

Answer 8

In slippery things (carTWOlage)

• Cartilage (including hyaline)
• Vitreous body
• Nucleus pulposus

Question 9

Where can you find type 3 collagen?

Answer 9

In bloody things

• Blood vessels
• Skin
• Uterus
• Fetal tissue
• Granulation tissue

Question 10

Which type of collagen is defective in Ehlers-Danlos?

Answer 10

Type 3 (threE D)

Question 11

Where can you find type 4 collagen?

Answer 11

Basement membrane or basal lamina (under the floor)

Question 12

In which disease is type 4 collagen defective?

Answer 12

Alport syndrome

Question 13

Mnemonic for Collagen?

Answer 13

1. Strong
2. Slippery
3. Bloody
4. BM (bowl movement)

Question 14

Where is the basic peptide of collagen synthesised?

Answer 14

Rough ER of fibroblasts

Question 15

What is the name of the primary protein produced in the production of collagen?

Answer 15

Preprocollagen

Question 16

1st step in synthesis of collagen?

Answer 16

Synthesis of preprocollagen alpha chains. Usually Gly-X-Y

Question 17

2nd step in synthesis of collagen and what does it require?

Answer 17

Hydroxylation of lysine and proline. Vitamin C

Question 18

No vitamin c leads to?

Answer 18

Scurvy

Question 19

3rd step in synthesis of collagen?

Answer 19

Glycosylation of hydroxylated lysine. Procollagen is the result. It is a triple helix of 3 collagen alpha chains. Hydrogen and disulfide bonds are used.

Question 20

4th step in synthesis of collagen?

Answer 20

Exocytosis of procollagen into extracellular space.

Question 21

Problems forming triple helix in collagen synthesis leads to?

Answer 21

Osteogenesis imperfecta

Question 22

5th step in synthesis of collagen?

Answer 22

Proteolytic cleavage of disulfide-rich terminal regions of procollagen, transfrorming it into insoluble tropocollagen

Question 23

6th step in synthesis of collagen?

Answer 23

Crosslink tropocollagen molecules to make collagen fibrils (by Cu2+ containing lysys oxidase). Covalent bonds between lysine and hydroxylysine

Question 24

Problems in cross linking tropocollagen into collagen causes?

Answer 24

Ehlers-Danlos

Question 25

A scar with too much collagen deposition?

Answer 25

Keloid

Question 26

Treatment of Keloids?

Answer 26

Injection of glucocorticoids

Question 27

OI type 1

Answer 27

- Autosomal dominant - Normal type 1 collagen but not enough - Multiple fractures - Blue sclerae - Hearing loss - Dental abnormalities

Question 28

OI type 2

Answer 28

- Autosomal recessive | - Perinatal lethal OI

Question 29

Classical Ehlers-Danlos syndrome

Answer 29

- Affects type 5 collagen (mainly) - Affects type 1 collagen - Hyperextensible skin - Joint hypermobility

Question 30

Vascular Ehlers-Danlos

Answer 30

- Affects type 3 collagen - Arterial rupture - Hemorrhages - Easy bruising - Berry aneurysms

Question 31

Alport syndrome

Answer 31

- Defect of type 4 collagen - Kidney disease - Hearing loss - Eye problems (Cataracts, Lenticonus) Can't see Can't pee Can't hear high C

Question 32

Where do you find Elastin?

Answer 32

- Blood vessels - Alveoli - Larynx - Ligamentum flavum

Question 33

What is elastin made of?

Answer 33

- Rich in Proline and glycine | - Non-hydroxylated

Question 34

How is elastin structured?

Answer 34

As tropoelastin. Held together by a matrix of fibrillin

Question 35

Where is fibrillin produced?

Answer 35

Fibroblast

Question 36

What's the defect in Marfan syndrome?

Answer 36

It's a defect in fibrillin

Question 37

Symptoms of Marfan

Answer 37

- Hyperelastic joints - Problems with heart valves, aorta - Very tall - Long arms and legs - Arachnodactyly - Steinberg sign - Pectus carinatum (pigeon chest)

Question 38

What breaks down elastin?

Answer 38

Elastase

Question 39

What inhibits elastase?

Answer 39

alpha-1-antitrypsin

Question 40

Alpha-1-antitrypsin deficiency characteristics

Answer 40

- Destruction of elastin in the alveoli - Emphysema - Liver problems (due to deficient a-1-a accumulating in liver)

Question 41

How are metalloproteases involved in angiogenesis?

Answer 41

They degrade the wall of existing vessels in order to facilitate branching

Question 42

What does VEGF do in existing vessels?

Answer 42

Signals to vascular endothelium to migrate towards place of need

Question 43

How is VEGF involved in angiogenesis when not branching from an existing vessel?

Answer 43

It can recruit from the bone marrow endothelial progenitor cells to the place og need and make new vessels that connect to the old vascular bed

Question 44

Cutaneous wound healing. 0-3 hours?

Answer 44

Hemorrhage and clotting

Question 45

Cutaneous wound healing. 12-24 hours?

Answer 45

Acute inflammation (PMNs) (Neutrophils)

Question 46

Cutaneous wound healing. 1-3 days?

Answer 46

- Macrophage infiltration - Granulation tissue (fibroblasts and vascular endothelial cells) - Epithelialization

Question 47

Cutaneous wound healing. Weeks-months?

Answer 47

Collagen production (type 3 then type 1)

Question 48

What aa's do you find a lot of in collagen?

Answer 48

Glycine, Proline, Hydroxyproline

Question 49

What aa's do you find a lot of in Elastin?

Answer 49

Glycine and Proline

Question 50

What's the role of vitamin C in collagen production?

Answer 50

Hydroxylation of lysine and proline