1H Foundations 8 - Extracellular environmant Flashcards
What protein is involved in transporting an endocytosed vesicle from the plasma membrane to the endosome?
Clathrin
Which metals are known to facilitate the generation of oxygen free radicals?
Iron and copper
Which tumor suppressor proteins prevent the progression of the cell into S-phase?
Rb and p53
- Most abundant protein in the body
- Extensively modified by posttranslational modification
- Organises and strengthens extracellular matrix
Collagen
Most common (90%) type of collagen
Type 1
Where can you find type 1 collagen?
In hard things (bONE)
- Bone
- Skin
- Tendon
- Dentin
- Fascia
- Cornea
- Late wound repair
Which type of collagen is defective in Osteogenesis imperfecta?
Type 1
Where can you type 2 collagen?
In slippery things (carTWOlage)
- Cartilage (including hyaline)
- Vitreous body
- Nucleus pulposus
Where can you find type 3 collagen?
In bloody things
- Blood vessels
- Skin
- Uterus
- Fetal tissue
- Granulation tissue
Which type of collagen is defective in Ehlers-Danlos?
Type 3 (threE D)
Where can you find type 4 collagen?
Basement membrane or basal lamina (under the floor)
In which disease is type 4 collagen defective?
Alport syndrome
Mnemonic for Collagen?
- Strong
- Slippery
- Bloody
- BM (bowl movement)
Where is the basic peptide of collagen synthesised?
Rough ER of fibroblasts
What is the name of the primary protein produced in the production of collagen?
Preprocollagen
1st step in synthesis of collagen?
Synthesis of preprocollagen alpha chains. Usually Gly-X-Y
2nd step in synthesis of collagen and what does it require?
Hydroxylation of lysine and proline. Vitamin C
No vitamin c leads to?
Scurvy
3rd step in synthesis of collagen?
Glycosylation of hydroxylated lysine. Procollagen is the result. It is a triple helix of 3 collagen alpha chains. Hydrogen and disulfide bonds are used.
4th step in synthesis of collagen?
Exocytosis of procollagen into extracellular space.
Problems forming triple helix in collagen synthesis leads to?
Osteogenesis imperfecta
5th step in synthesis of collagen?
Proteolytic cleavage of disulfide-rich terminal regions of procollagen, transfrorming it into insoluble tropocollagen
6th step in synthesis of collagen?
Crosslink tropocollagen molecules to make collagen fibrils (by Cu2+ containing lysys oxidase). Covalent bonds between lysine and hydroxylysine
Problems in cross linking tropocollagen into collagen causes?
Ehlers-Danlos
A scar with too much collagen deposition?
Keloid
Treatment of Keloids?
Injection of glucocorticoids
OI type 1
- Autosomal dominant
- Normal type 1 collagen but not enough
- Multiple fractures
- Blue sclerae
- Hearing loss
- Dental abnormalities
OI type 2
- Autosomal recessive
- Perinatal lethal OI
Classical Ehlers-Danlos syndrome
- Affects type 5 collagen (mainly)
- Affects type 1 collagen
- Hyperextensible skin
- Joint hypermobility
Vascular Ehlers-Danlos
- Affects type 3 collagen
- Arterial rupture
- Hemorrhages
- Easy bruising
- Berry aneurysms
Alport syndrome
- Defect of type 4 collagen
- Kidney disease
- Hearing loss
- Eye problems (Cataracts, Lenticonus)
Can’t see
Can’t pee
Can’t hear high C
Where do you find Elastin?
- Blood vessels
- Alveoli
- Larynx
- Ligamentum flavum
What is elastin made of?
- Rich in Proline and glycine
- Non-hydroxylated
How is elastin structured?
As tropoelastin. Held together by a matrix of fibrillin
Where is fibrillin produced?
Fibroblast
What’s the defect in Marfan syndrome?
It’s a defect in fibrillin
Symptoms of Marfan
- Hyperelastic joints
- Problems with heart valves, aorta
- Very tall
- Long arms and legs
- Arachnodactyly
- Steinberg sign
- Pectus carinatum (pigeon chest)
What breaks down elastin?
Elastase
What inhibits elastase?
alpha-1-antitrypsin
Alpha-1-antitrypsin deficiency characteristics
- Destruction of elastin in the alveoli
- Emphysema
- Liver problems (due to deficient a-1-a accumulating in liver)
How are metalloproteases involved in angiogenesis?
They degrade the wall of existing vessels in order to facilitate branching
What does VEGF do in existing vessels?
Signals to vascular endothelium to migrate towards place of need
How is VEGF involved in angiogenesis when not branching from an existing vessel?
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
Cutaneous wound healing. 0-3 hours?
Hemorrhage and clotting
Cutaneous wound healing. 12-24 hours?
Acute inflammation (PMNs) (Neutrophils)
Cutaneous wound healing. 1-3 days?
- Macrophage infiltration
- Granulation tissue (fibroblasts and vascular endothelial cells)
- Epithelialization
Cutaneous wound healing. Weeks-months?
Collagen production (type 3 then type 1)
What aa’s do you find a lot of in collagen?
Glycine, Proline, Hydroxyproline
What aa’s do you find a lot of in Elastin?
Glycine and Proline
What’s the role of vitamin C in collagen production?
Hydroxylation of lysine and proline
