Lysosome Flashcards
1
Q
What is significant about the lysosome membrane?
A
It is heavily glycosylated to protect the lysosome from degrading itself
2
Q
What are lysosomes filled with?
A
acid hydrolases
3
Q
What is the pH in a lysosome?
A
4.5-5
4
Q
Proteases, nucleases, lipases, phospholipases, phosphatases, sulfatases are all examples of what?
A
acid hydrolases (what fill lysosome)
5
Q
What is a primary lysosome?
A
newly synthesized with acid hydrolases but have not yet aquired material or degraded anything
6
Q
What is a secondary lysosome?
A
a lysosome that has or is degrading something
7
Q
What is TGN?
A
trans golgi network
8
Q
Primary lysosomes bud from what?
A
trans golgi network
9
Q
If a vesicle is going from golgi to endosome what is the only thing it carries?
A
lysosomal enzymes
10
Q
What goes from an endosomeo to golgi?
A
membrane and M6P receptors
11
Q
how does an endosome become a lysosome?
A
Combination of fusing and lowering of pH due to proton pumps
12
Q
Where do vesicles that contain material to be degraded go once they enter cell via endocytosis?
A
They go to early endosome then to late endosome then to lysosome (the endosome becomes these things)
13
Q
After a vesicle leaves the TGN, what are its three options?
A
- Constitutive secretion
- Regulated secretion
- Lysosomal/endosomal pathways
14
Q
When a vesicle has a clathrin coat, where is it going?
A
lysosome or endosome
15
Q
What is the purpose of GlcNAc phosphotransferase
A
It puts the M6P tag on the protein in the cis Golgi
16
Q
What does M6P tag have a high affinity for?
A
M6P receptor in TGN
17
Q
What puts the sugar chains on the protein in the rER?
A
Dolichol
18
Q
What is the function of dolichol?
A
puts on n-linked oligosaccharide chains on in rER
19
Q
Where is the only location clathrin will coat vesicle?
A
From golgi to lysosome or endosome, and from plasma membrane into a cell.
20
Q
When a vesicle coated in clathrin buds off, what allows the final “budding” or “pinching” off of the vesicle from the membrane?
A
dynamin GTPase
21
Q
When will COPII form?
A
vesicle going from ER to golgi
22
Q
When will COPI form?
A
vesicle going from golgi to ER
23
Q
How do hydrolases get into lysosome?
A
Cargo binds M6P receptor M6P receptor clusters →adaptors →clathrin vesicle buds off clathrin removed fusion with endosome acidic enviornment → M6P receptor dissociates Phosphate removed from cargo M6P recycled back to TGN
24
Q
Why does phosphate need to be removed from cargo?
A
So it cannot bind back to M6P receptor
25
What is the name of the pump that pumps H+ into lysosome?
V-type ATPase
26
If lysosome fuses with extracellular membrane, where would the glycosylation face?
extracellular space (in the lysosome, they face the lumen)
27
What are the 3 pathways to degradation in lysosome?
Endocytosis
Phagocytosis
Autophagy
28
Phagosomes fuse with what?
lysosome
29
What is autophagy?
the cell is digesting something w/in itself
30
What do organelles (EX: mitochondria) that are not needed or are too old in a cell do to be degraded?
They form autophagasome and fuse with lysosome
31
What is a multivesicular body?
an intermediate step b/w early endosome and late endosome
32
If you want to down regulate a receptor because a cell has enough of a substance, how would you degrade a transmembrane protein?
multivesicular body - the membrane fuses together and creates areas inside the cell where the transmembrane protein can be, which will eventually be degraded
33
How does the lysosome/endosome know when a receptor is no longer needed and needs to be degraded?
it will be mono-ubiquinated
34
What is mono-ubiquitin tag?
It downregulates receptors/proteins
35
What is the product when a phagosome joins with a lysosome and digests the material?
Residual body & indigestible material
36
If product accumulates in cytosol after lysosome and phagosome degrade, what is it called?
lipofucin
37
Describe what happens in autophagy
ER envelopes old organelle, then fuses with a lysosome
38
What envelopes old organelles for autophagy?
ER
39
If lysosome can't degrade material within it, it becomes a ______
residual body
40
What happens to residual body?
it is expelled from cell or remains in cell as lipofuscin
41
Pigmented lipids that accumulate in organs is what?
lipofuscin
42
What is the mode of inheritance for lysosomal storage diseases?
recessive
43
Most lysosomal storage diseases affect what?
individual hydrolase
44
What is the most sever lysosomal storage disease?
I-cell disease
45
Explain the gist of a lysosomal storage disease
hydolase doesn't work correctly →accumulation in lipid →enlarged lysosomes →inhibits function of cell
46
Tay Sachs is what kind of disease?
lysosomal storage
47
Gaucher is what kind of disease?
lysosomal storage
48
What are gags?
glycosaminoglycans (basically sulfated sugars)
49
Mucopolysaccharidoses is what kind of disease?
lysosomal storage
50
Metachromatic leukodystrophy is what kind of disease?
lysosomal storage
51
pseudo-Hurler polydystrophy is what kind of disease?
lysosomal storage
52
Mucopolysaccharidoses has the accumulation of what?
GAGs
53
Metachromatic leukodystrophy has the accumulation of what?
sulfatides
54
pseudo-Hurler polydystrophy is similar to what disease?
I-cell, but not as severe
55
key words: absence of M6P, waste products in inclusion bodies, coarse facial features, enlarged liver/spleen, death CHF are what disease?
I-cell
56
What is the mechanism for I-cell?
Acid hydrolases lack H6P so are secreted extracellulary, build up of stuff in lysosome
57
These characteristics: later onset than I Cell, survival into adulthood are linked to what disease?
Pseudo-Hurler Polydystrophy (MUCOLIPIDOSIS III)
58
what is Hirsutism?
excessive facial hair
59
Characteristics: alpha-L-iduronidase, dermatan sulphate & heparan sulphate, hepatosplenomegaly, coarse facial features, skeletal deformity, hirsutism, corneal clouding are what disease?
Hurler Syndrome
60
MPS IH stands for what?
Hurler syndrome
61
```
Symptoms: Physical & mental deterioration
Growth stops at 2-4 yrs
Hepatosplenomegaly
Deafness
Skeletal deformity
Coarse facial features
Hirsutism
Thickened skin
Corneal clouding
at a few months old is what disease?
```
Hurler syndrome
62
Which disease has a deficiency of α-L-iduronidase ?
Hurler syndrome
63
Deficiency of α-L-iduronidase causes what?
accumulation of dermatan sulphate & heparan sulphate
64
accumulation of dermatan sulphate & heparan sulphate is what disease?
hurler syndrome
65
What are dermatan sulphate & heparan sulphate ?
2 kinds of GAGs
66
Characteristics: Milder form of Hurler Syndrome are what disease?
Scheie & Hurler-Scheie Syndrome
67
What disease has residual α-L-iduronidase activity?
Scheie & Hurler-Scheie syndrome
68
MPS IS & MPS IHS stands for what?
Scheie & Hurler-Scheie syndrome
69
MPS IS is what?
Schaeie syndrome
70
MPS IHS is what?
Hurler-scheie syndrome
71
Of the MPS diseases, rank from most severe to least severe
IH - IHS - IS
72
Characteristics: later presentation (2-4 years old) and milder course, surviving into mid 30s, no corneal clouding is what disease?
Hunter syndrome
73
Key words: iduronodate sulphatase, no corneal clouding is what disease?
Hunter syndrome
74
MPS II is what disease?
Hunter syndrome
75
What is the mode of inheritance for hunter syndrome?
x-linked recessive
76
how is the mod of inheritance different in hunter syndrom from other lysosomal storage syndromes?
Most are autosomal recessive, hunter is x-linked recessive
77
Deficiency of enzyme iduronodate sulphatase is what disease?
Hunter syndrome
78
Hunter syndrome has deficiency of what enzyme?
iduronodate sulphatase
79
dermatan sulphate & heparan sulphate are examples of what?
GAGs
80
What is the mechanism for Hunter syndrome?
Deficient iduronodate sulphatase ! accumulation of dermatan sulphate & heparan sulphate (GAGs)
81
What kind of disease is Sanfilippo syndrome ?
Lysosomal storage
82
MPS III stands for what?
Sanfilippo syndrome
83
Key words: short, pectus carinatum, normal IQ; Often mistaken for skeletal dysplasia rather than lysosomal storage disease are what disease?
Morquio Syndrome (MPS IV)
84
Symptoms: normal IQ, short stature, pectus carinatum (pigeon chest), aortic regurgitation ! cardiomegaly, deafness, weakness are what disease?
Morquio Syndrome (MPS IV)
85
What disease has Defective degradation of keratan sulphate
Morquio Syndrome (MPS IV)
86
What is MPS IV?
Morquio Syndrome
87
What lysosomal storage disease is often misdiagnosed as skeletal dysplasia?
Morquio syndrome
88
What is the mechanism of Morquio syndrome?
accumulatino of GAGs due to defective degradation of keratan sulphate
89
Characteristics: Similar to Hurler with normal IQ are what disease?
Maroteaux-Lamy Sydrome (MPS VI)
90
MPS VI is what disease?
Maroteaux-Lamy Sydrome
91
MPS VII is what disease?
Sly syndrome
92
What disease has deficient ARSA (Arylsulfatase A)?
Metachromatic Leukodystrophy
93
What kind of disease is Metachromatic Leukodystrophy?
lysosomal storage
94
What is the mechanism for Metachromatic Leukodystrophy?
Deficient ARSA → defective degradation of sulfatides → accumulation of sulfatides in cells → progressive leukodystrophy in CNS & PNS → paralysis & cognitive decline
95
How severe is Metachromatic Leukodystrophy?
Depends on age of onset, three different forms
96
Key words: CHS1/LYST, phagocytosis, autophagocytosis, recurrent infections are what disease?
Chediak-Higashi Syndrome
97
Recurrent infections (life threatening), hypopigmentation, mild coagulation defects, varying neurological problems; Treatment = BMT (hematologic & immune defects) is what disease?
Chediak-Higashi Syndrome
98
What is CHS1/LYST?
lysosomal trafficking regulatory protein involved in vesicle fusion). Know that it is involved in vesicle fusion
99
What kind of disease is Chédiak-Higashi syndrome
| ?
Not lysosomal storage - but related to lysosomal function
100
What is the mechanism for Chediak-Higashi syndrome?
Mutated CHS1/LYST: delayed fusion of phagosome with lysosome in leukocytes & granular defects in NK cells →recurrent infections; granular defects in platelets →coag. defects; autophagocytosis of melanosomes in melanocytes → albinism
101
What membrane is similar to lysosomal membrane?
Melanocytes
102
What are NK cells?
natural killer
103
Besides Hurler, what other disease has the accumulation of dermatan sulphate & heparan sulphate?
Hunter Syndrome
