Term
| Vesicles exiting the TGN have 3 choices: |
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Definition
1. Constitutive secretion- always happening
2. Regulated Secretion
3. Lysosomal / endosomal pathway
(Proteins for this choice are tagged in cis-Golgi with mannose-6-Phosphate) |
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Term
| Where and by what is the Mannose-6-Phosphate put on the lysosomal proteins? |
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Definition
Put on in CIS GOLGI BY
N-ACETYL-GLUCOS-AMINE
PHOSPHO-TRANSFERASE
(NAG-PT) |
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Term
| MP6 Tag put on in cis Golgi by ... |
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Definition
| GlcNAc phosphotransferase |
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Term
| What pumps H+ into lysosome, maintaining acidic pH? |
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Definition
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Term
| What is the Lysosomal membrane made up of? |
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Definition
| Lots of lipids & proteins so = heavily glycosylated; protection from digestion |
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Term
| What are Multivesicular bodies? |
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Definition
The step in between the maturation of early endosomes which contain endocytic vesicles to late endosomes.
MVBs shed vesicles to recycle material back to PM
Gradually convert into late endosomes by fusing with eachother / with other late endosomes |
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Term
| If lysosome can’t degrade material within it, what does it become? |
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Definition
| If lysosome can’t degrade material within it, it becomes a residual body, and either expels material from the cell or it remains as lipofuscin |
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Term
| What is Gaucher's disease? |
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Definition
Lysosomal storage disease
Lipid storage disorders
(accumulation of glucocerebroside) |
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Term
| I-cell disease (Mucolipidosis II) |
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Definition
Deficiency of N-acetylglucosamine phosphotransferase
→ Absense of M6P tag
THIS ENZYME NORMALLY FUNCTIONS IN THE CIS GOLGI. |
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Term
| What is so bad about I-cell disease?! |
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Definition
Acid hydrolases lacking M6P are secreted extracellularly
→ Undigested substrates accumulate as inclusion bodies, progressively damages cells
HIGH LEVELS OF ENZYMES IN BLOOD
FOR EDDIE –CORNEAL CLOUDING!!!!!!!!!!!!!!!!!!!
Skeletal abnormalities (lack of growth)
Coarse features
Restricted joint movement
Psychomotor retardation
Enlarged liver, spleen, heart valves
Death CHF / RTI
Life expectancy <10yrs |
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Term
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Definition
Most common lysosomal storage disease
Deficiency of glucocerebrosidase
→ accumulation of glucocerebroside (a glycosphingolipid)
in macrophages = Gaucher’s cells
Progressive hepatosplenomegaly
Hypersplenism → increased destruction of RBCs, WBCs & platelets |
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Term
| What type of gauchers disease are most common? |
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Definition
Types I – III
Type I = 99% cases: No brain involvement
Progressive CNS involvement in types II & III (convulsions, hypertonia, mental retardation or dementia). Type II more severe |
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Term
What is Hurler syndrome (MPS IH)?
TYPE of Mucopolysaccharidoses |
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Definition
Most severe MPS
Deficiency of α-L-iduronidase
→ accumulation of dermatan sulphate & heparan sulphate
Autosomal Recessive! |
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Term
| What happens in Hurler syndrome (MPS IH)? |
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Definition
At few months old:
Physical & mental deterioration
Growth stops at 2-4 yrs
Hepatosplenomegaly
Deafness
Skeletal deformity
Coarse facial features
Hirsutism
Thickened skin
Corneal clouding
Death ≤10 yrs |
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Term
| What is Hunter syndrome (MPS II)? |
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Definition
Deficiency of iduronodate sulphatase (X-linked)
→ accumulation of dermatan sulphate & heparan sulphate
Similar to Hurler syndrome
BUT
Later presentation (2-4 yrs) &
milder course (survival into 30’s)
no corneal clouding
X-linked, not autosomal recessive
A WAY TO REMEMBER IT:
Men (X linked) are HUNTERS who NEED TO SEE (NO CORNEAL CLOUDING!!!) |
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Term
| What is Chédiak-Higashi syndrome? |
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Definition
Mutation CHS1/LYST = lysosomal trafficking regulatory protein normally involved in vesicle fusion
Delayed fusion of phagosome with lysosome in leucocytes
Autophagocytosis of melanosomes in melanocytes → albinism
Granular defects in NK cells & platelets
Recurrent infections (life threatening)
Hypopigmentation |
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