Endosome- Lysosome System and Cell Digestion Flashcards
1
Q
Accumulation of GM2
A
Tay-Sachs Disease
2
Q
In vivo, whole areas of tissue are affected. Necrosis or apoptosis.
A
Necrosis
3
Q
- Treatment for Gaucher Disease
A
- Enzyme replacement therapy- successful in alleviating non CNS symptoms
- Administer correct enzyme which has been engineered to be endocytosed by macrophages
- Enzymes delivered to lysosomes- breakdown of glucosylceramide
- Doesn’t work on types 2 and 3
4
Q
Treatment of Tay- Sachs Disease
A
- ERT has been unsuccessful
- The blood-brain barrier makes access difficult
- Neurons are not phagocytic
5
Q
Gene symbol: GNPTAB
A
Mucolipidosis IIa/B (I- Cell Disease)
6
Q
Transcytosis is crucial to maintaining cell __________
A
Polarity
7
Q
_____________ is an anti-apoptotic protein which inhibits release of _______ from mitochondria
A
Bcl-2; Cytochrome c
8
Q
Is LDL good or bad cholesterol?
A
Bad
9
Q
Vesicular trafficking delivers contents of _______________ to target organelles.
A
Vesicle
10
Q
In this type of cell death, the process is rapid and uses intracellular enzymes, and leaves no trace
A
Apoptosis
11
Q
During _______, apoptosis removes webs between fingers and toes or neurons which make the wrong connections
A
Morphogenesis
12
Q
Transcytosis (IgA) pathway
A
- IgA dimerizes
- IgA dimers bind to IgA receptor
- IgA and receptor complex internalized
- Clathrin coated vesicles forms
- Clathrin coat falls off
- Early endosome fuses with CRE
- IgA and receptor “recycled” to apical membrane
- Receptor clipped by enzyme to release IgA molecules
13
Q
How does the H+ ATPase pump impact lysosomes?
A
It helps to maintain a low pH by pushing H+ ions into the lysosome
14
Q
What are some come symptoms of lysosomal storage disorders?
A
Neuropathies, kidney disease, bone malformations, muscle diseases, and general failure to thrive
15
Q
Mucolipidosis IIa/B (I- Cell Disease)
A
Adds mannose-6-phosphate to lysosomal enzymes
16
Q
Cellular swelling. Necrosis or apoptosis
A
Necrosis
17
Q
Some intermediates in fatty acid oxidation act as ____________ molecules
A
Signaling
18
Q
Mutations of p53 protein are common in what type of disease?
A
Cancer
19
Q
Cell is phagocytosed, no tissue reaction. Necrosis or apoptosis.
A
Apoptosis
20
Q
Trafficking of Lysosomal Hydrolases (Pathway)
A
- Manose 6-phosphate moiety added to hydrolases in Golgi
- Enzymes partitioned into clathrin coated vesicles by M6P receptor
- Clathrin Coated vesicles bud off trans Golgi network and fuse with late endosomes
- At lower pH, hydrolases dissociate from the M6P receptors
- Empty receptors are recycled to the Golgi for further rounds of transport
21
Q
What happens in necrosis?
A
- Cellular contents spill into the surrounding tissues
- Inflammation develops
22
Q
What process takes place in internal apoptosis?
A
Release of cytochrome c activates a caspase cascade
23
Q
LDL Endocytosis PATHWAY
A
- LDL binds to its receptor
- LDL and receptor are internalized
- Clathrin coated vesicles forms
- Clathrin coat falls off
- Early endosome fuses with the Sorting Early Endosome
- LDL dissociates from its receptor
- LDL traffiscked to Late Endosome and lysosome
- LDL receptor recycled back to plasma membrane
24
Q
DNA fragmentation is random. Necrosis or apoptosis.
A
Necrosis
25
Lysosomal delivery and degradation of intracellular organelles
Autophagy
26
Though these macromolecules cannot be oxidized by mitochondria, they can be oxidized by peroxisomes.
Long chain fatty acids
27
Peroxisomes play a major role in \_\_\_\_\_\_\_\_\_\_\_metabolism in the cell
Lipid
28
Symptoms of Tay Sachs Disease
1. Hypotonia
2. Decreased muscle strength and spasticity leading to ataxia and paralysis
3. Startle response
4. Blindness
5. Deafness
6. Cognitive decline
7. Infantile: fatal in childhood
8. Juvenile: onset between 2 and 10
9. Adult- onset in 30s or 40s
29
Ligands and receptors have different fates depending on the ____________ and trafficking route inside the cell.
Receptor
30
Early Endosome marker
Rab 5
31
Are all members of the Bcl-2 family anti-apoptotic?
No, some are pro-apoptotic
32
Types of endocytosis that is non-selective
1. Phagocytosis
2. Pinocytosis
33
What is vesicular trafficking?
A basic cellular process in which membrane- bound carriers bud off the donor compartment and fuse with the receipt one.
34
What is autophagy used for?
1. Organelle removal and turnover
2. A source of nutrient during “starvation”
3. Degradation of long-lived, aggregated or misfolded proteins
35
Lysosome marker
LAMP1, LAMP2, LAMP3
36
Peroxisomes contain a variety of _________ enzymes, including catalase.
Oxidative
37
Fast recycling marker
Rab 4
38
Gene symbol GBA
Gaucher Disease
39
A chloride channel protein is mutated in \_\_\_\_\_\_
Cystic fibrosis
40
Cells with DNA damage are monitored by what protein?
P53
41
Trafficking of Lysosomal Hydrolases Pathway
1. Mannose-6-phospahate moiety added to hydrolases in cis Golgi.
2. Enzymes partitioned into clathrin coated vesicles by M6P receptor in trans golgi
3. CCVs bud off trans golgi network and fuse with late endosomes
4. At lower pH, hydrolases disscoiate from the M6P receptors
5. Empty receptors are recycled to the Golgi for further rounds of transport.
42
Enzymes found in lysosomes
1. Nucleases
2. Proteases
3. Glycosidases
4. Lipase
5. Phosphatases
6. Sulfatases
7. Phospholipases
43
In transferrin endocytosis, the ligand is ________ and the receptor is \_\_\_\_\_\_\_\_\_.
Recycled; recycled
44
Gene symbol: HEXA
Tay-Sachs Disease
45
Oxidation produces __________ as a by-product.
Hydrogen peroxide
46
Which cell types would lipofuscin granules accumulate in?
Heart muscle, neurons, retina
47
Late endosome pH
5.5
48
Before vesicle can be off loaded, v-snare must bind to \_\_\_\_\_\_\_\_\_\_\_\_.
t-snare
49
Enzyme reaction for Gaucher Disease
Glucosylceramide + H20 -\> Ceramide +Glucose
50
Internally or externally induced. Necrosis or apoptosis.
Apoptosis
51
In LDL endocytosis, the ligand is __________ and the receptor is \_\_\_\_\_\_\_\_\_\_\_.
Degraded; recycled
52
What process takes place in external apoptosis?
Fas ligands bind to Fas receptors on the cell surface to activate a caspase cascade
53
Can peroxisomes divide?
Yes
54
Defective protein of Gaucher Disease
Glucocerebrosidase (GCase)
55
Defective protein in Tay-Sachs Disease
beta-N-acetylhexosaminidase (a- subunit)
56
Where might lysosome related organelles be found?
Melanocytes
T-lymphocytes
Platelets
57
The lysosome must be uncoated to _________ with the late endosome
Fuse
58
What is the process of macro-autophagy in starvation conditions?
1. Rag-GTPase becomes GDP bound and no longer associated with the lysosome membrane.
2. mTORC1 is dephosphorylated and dissociates from Rag-GTPases
3. TFEB is dephosphorylated and translocates to the nucleus
4. TFEB turns on the transciption of the genese needed for autophagy and lysosome biogenesis
5. Macro-autophagy occurs
6. Nutrients are generated, and Rag-GTPases return to GTP bound form
59
Vesicular sorting is ___________ specific
Cargo
60
Regulates normal growth and differentiation
Epidermal Growth Factor (EGFR)
61
In vivo: individual cells appear affected. Apoptosis or necrosis
Apoptosis
62
In this type of endocytosis only what gets bound to the receptor will be engulfed.
RME
63
Externally induced only. Necrosis or apoptosis.
Necrosis
64
\_\_\_\_\_\_\_\_\_\_\_\_\_- tagged cytoplasmic and nuclear proteins are destroyed by proteasomes.
Ubiquitin
65
Autophagy and Neuro-degeneration disorders
Parkinson's
Huntington's
ALS
66
Catalase converts ________ to \_\_\_\_\_\_\_\_.
H2O2; H2O
67
Once dissociated from transferrin, where does the Fe++ go?
The cytoplasm
68
Cellular defect of Mucolipidosis IIa/B (I-Cell Disease)
1. Lysosomal enzymes are secreted instead of being delivered to lysosomes
2. Many substances accumulate in lysosomes making inclusion bodies
3. Not all cells are affected. There are other ways for enzymes to get to the enzyme
69
Slow recycling marker
Rab 11
70
What is the importance of the ubiquitin tag?
It notifies the cell that the tagged molecule needs to be degraded
71
What diseases are caused by protein aggregates?
Alzheimer's or Huntington's
72
What shape are peroxisomes?
Spherical
73
Activation of ________ triggers apoptosis
Caspases
74
\_\_\_\_\_\_\_\_\_\_\_\_\_\_ transport lipids around the body through the blood.
Lipoproteins
75
Cell ingestion of material from outside of the cell is called \_\_\_\_\_\_\_\_\_\_\_\_\_.
Endocytosis
76
\_\_\_\_\_\_\_\_\_\_\_ is caused by damage and leads to cell swelling and rupture
Necrosis
77
Late endosome marker
Rab 7
78
Proteosome degradation inactivates the \_\_\_\_\_\_\_\_
Cyclin-Cdk complex
79
\_\_\_\_\_\_\_\_\_\_\_\_ have a lysosomal storage disorder
1/5000th
80
How many molecules can transferrin carry at one time?
Up to two
81
EGFR Endocytosis Pathway
1. Ligand binds to EGFR and receptor dimerizes
2. Ubiquitin binds to the receptor
3. EGFR complex internalized
4. Clathrin coated vesicles form
5. Clathrin coat falls off
6. Early endosome fuses with the sorting early endosome
7. EGFR complex trafficked to lysosome through the late endosome
8. Entire EGFR complex digested by the lysosome
9. EGF signaling cascade turned off
82
Ladder like DNA fragmentation. Apoptosis or necrosis
Apoptosis
83
Some viruses are able to inhibit apoptosis by making a __________ like protein.
Bcl-2
84
In starvation conditions, ________ is no longer associated with the lysosome membrane.
Rag-GTPase
85
Symptoms of I-Cell Disease
1. Failure to thrive
2. Developmental delays
3. Abnormal skeletal development
4. Restricted joint movement
5. Hepatosplenomegaly
6. Fatal in early childhood
86
An autophagosome is a spherical structure with ___________ membranes.
Double layered
87
\_\_\_\_\_\_\_\_\_ are required for plasmalogen synthesis.
Peroxisomes
88
pH of lysosome
4.5
89
Treatment for I- Cell Disease
1. Enzyme replacement therapy has been unsuccessful
2. Gene therapy is a possible therapy
3. Transporting enzymes to the Golgi
90
Early endosome pH
6.5
91
What does p53 trigger?
DNA REPAIR OR APOPTOSIS
92
Transferrin Endocytosis
1. Fe3+- transferrin bound to receptor
2. Transferrin complex is internalized
3. Clathrin coated vesicle forms
4. Clathrin coat falls off
5. Early endosome fuses with Sorting Early Endosome
6. Fe3+ dissociates from transferrin
7. Fe 3+ transported to cytoplasm for use in metabolism
8. Transferrin and receptor recycled back to plasma membrane
9. Transferrin dissociates from receptor
93
Cellular condensation/ shrinking. Necrosis or apoptosis
Apoptosis
94
Membrane remains intact until the cytoplasm pinches off because of blebbing. Necrosis or Apoptosis
Apoptosis
95
What is the major phospholipid in myelin?
Plasmalogen
96
Accumulation of Glucosylceramise
Gaucher Disease
97
What type of proteins are digested by proteasomes?
1. Misfolded
2. Short-lived
3. Abnormal
4. Unneeded proteins
98
Plasma glycoproteins that transports iron
Transferrin
99
\_\_\_\_\_\_\_ is cellular suicide
Apoptosis
100
After leaving the Golgi, the vesicle either goes to the ___________ or \_\_\_\_\_\_\_\_\_\_\_\_.
Lysosome; plasma membrane
101
Symptoms of Type 1 Gaucher Disease
1. Non-neuropathic Gaucher Disease
2. Most common
3. Hepatosplenomegaly because macrophages cannot completely digest aged RBC
4. Anemia, thrombocytopenia, lung disease, and bone abnormalities
102
Lysosomal storage disorders result in the accumulation of a ___________ in the lysosome.
Substrate
103
What is the major degradative compartment in eukaryotic cells?
Lysosome
104
Proteasomes digest __________ proteins
Misfolded
105
Lysosome enzymes are made in the \_\_\_\_\_\_\_\_\_\_\_\_, then transferred to the \_\_\_\_\_\_\_\_\_\_\_\_, which then becomes a lysosome.
ER; endosome
106
Lysosome size
0.5-1.0 µm
107
Lysosomal storage disorders usually result in a __________ defect in a single lysosomal enzyme.
Genetic
108
Receptor- Mediated Endocytosis Steps
1. Ligands bind receptors at cell surface
2. Ligand-bound receptors cluster in clathrin- coated pits
3. Coated pits form coated vesicles
4. Receptors and ligands go to early endosomes
109
What is the difference between lysosomes and lysosome related organelles?
Lysosome relate organelles are cell specific
110
Endosome turns into\_\_\_\_\_\_\_\_\_
Lysosome
111
\_\_\_\_\_\_\_\_\_\_diseases can be caused by misfolded proteins.
Prion
112
Endosomes are also known as \_\_\_\_\_\_\_\_\_\_\_\_\_
Multi-vesicular bodies
113
Types of endocytosis
1. Phagocytosis
2. Pinocytosis
3. Receptor- mediated endocytosis (RME)
114
Are lysosomes heterogeneous or homogeneous ?
Heterogeneous
115
ATP depleted. Necrosis or apoptosis.
Necrosis
116
Lysosome and Neuro-degeneration disorders
Gaucher's Disorder
Alzheimer's Disease
117
Symptoms of Type 2 Gaucher Disease
1. Neuropathic forms
2. Type 1 symptoms, abnormal eye movements, seizures, and brain damage
3. Type 2 is lethal in infancy
4. Type is slower progressing
118
Which type of cell death requires ATP?
Apoptosis
119
Enzyme reaction Tay- Sachs Disease
GM2-\>GM3
120
Transcytosis occurs in __________ cells
Epithelial cells
121
3 steps to Autophagy
1. Initiation
2. Elongation and Closure
3. Degradation
122
End products of lysosomal digestion
Lipofuscin granules
