Protein Digestion, Lysosomes Flashcards

1
Q

Where do amino acids come from?

A
  1. Degradation of proteins

2. Synthesis of AAs from glycolytic or TCA intermediates (only 10 AAs can be made this way, the rest come from our diet)

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2
Q

List 3 ways that proteins are degraded to attain AAs

A
  1. Ubiquitin/Proteasome System
  2. Digestive Enzymes
  3. Lysosomes
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3
Q

When proteins are degraded, what happens to the nitrogen in AAs?

A

Nitrogen in AAs can be recycled, but excess Nitrogen is excreted

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4
Q

True or False: Because we excrete excess Nitrogen, we need a consistent intake of Nitrogen from our diet.

A

True

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5
Q

Name 3 digestive enzymes (in the zymogen form)

A
  1. Pepsinogen
  2. Trypsinogen
  3. Chymotrypsinogen
    (also proelastase and procarboxypeptidase)
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6
Q

What organ(s) release digestive enzymes?

A

Pancreas and stomach

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7
Q

True or False: Digestive enzymes are stored as inactive zymogens so they do not degrade our own proteins

A

True

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8
Q

Which cells secrete pepsinogen, and where is it secreted into?

A

Chief cells release pepsinogen in the stomach

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9
Q

Discuss the structure of inactive pepsinogen and what low pH does to the zymogen

A
  • Inactive pepsinogen has an N-terminal segment blocking the active site
  • When pepsinogen is exposed to low pH, it undergoes conformational change and auto-cleavage to form Pepsin
  • at low pH, the electrostatic interactions between the N terminal segment and the rest of the protein are destabilized so now the active site is exposed
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10
Q

What organ releases serine proteases (trypsin, chymotrypsin, elastase, carboxypeptidase)?

A

The pancreas

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11
Q

What is the optimal pH of the serine proteases to be in?

A

~7

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12
Q

Name the serine protease that is anchored to the outer membrane of small intestinal epithelial cells

A

Enteropeptidase

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13
Q

What is the function of enteropeptidase?

A

It cleaves trypsinogen to activate trypsin

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14
Q

True or False: When trypsinogen is cleaved into typsin, trypsin can further activate trypsinogen to convert into trypsin

A

True

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15
Q

True or False: When trypsin is activated, it can activate chymotrypsinogen, proelastase, and procarboxypeptidase into their active forms

A

True (known as cascade of proteolytic cleavages)

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16
Q

_____ _____ _____ is stored along with zymogens inside the pancreas.

A

Pancreatic Trypsin Inhibitor (PTI)

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17
Q

What AA does PTI have that allows it to bind closely to trypsin?

A

Lysine

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18
Q

True or False: Enteropeptidase cleaves a bond between Lysine and Isoleucine

A

True

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19
Q

What organelle do lysosomes originate from?

20
Q

What do lysosomes contain?

A

Various digestive enzymes in an acidic environment

21
Q

True or False: Substrates for lysosomes come from fusion with other vesicles.

22
Q

What is the function of lysosomes?

A

Breakdown and recycle cellular components

23
Q

True or False: There is a V-type ATPase on the membrane of lysosomes which works to pump protons INSIDE the lysosome, maintaining acidity

24
Q

Name 4 lysosomal enzymes

A
  1. Lipases
  2. Amylases
  3. Proteases
  4. Nucleases
25
True or False: There are no proteins on the membrane of lysosomes that are essential for allowing vesicles to fuse w/ the lysosome
False
26
What do lysosomes degrade?
Lipids, proteins, nucleic acids, invading pathogens
27
What is autophagy used for?
Degrading big cellular stuff, like mitochondria
28
What factors activate autophagy? (3 things)
1. Stress/Damage 2. Starvation 3. Invading pathogens
29
What factors inhibit autophagy? (2 things)
1. Nutrient abundance (insulin) | 2. Microbial Virulence Factors
30
Where does the isolation membrane come from in autophagy?
The ER
31
Once the autolysosome has been formed by fusing the autophagosome w/ the lysosome, the _______ membrane is removed and the contents are degraded.
Inner membrane
32
What is the primary method of degrading proteins?
Proteasome/Ubiquitin System
33
What is the following protein: a 76 residue protein which is covalently attached to target proteins.
Ubiquitin
34
True or False: Ubiquitin is found only in eukaryotes, it is highly conserved, and there is only one method of Ub modification.
False - the first 2 statements are true but the last is false.
35
List the name of the enzymes involved in ubiquitin activation
E1, E2, E3
36
True or False: E1 does not require ATP-dependent activation.
False
37
True or False: MonoUb signals for DNA repair, nucleear export, autophagy, endocytosis, etc. However, PolyUb signals for proteasomal degradation.
True
38
What is the function of DeUBiquitinases?
Hydrolyze isopeptide bonds between Ub and a target protein (Ub is recycled not degraded)
39
What residue length are peptides that are generated by the proteasome?
2-15 residue long, further degraded by cellular peptidases
40
What is architecture of the proteasome?
- Two 19S regulatory particles (with 18 proteins in each) | - 20S core particle in the middle. 2 rings of alpha subunits, 2 rings of beta
41
What is the function of beta subunits?
They form the proteolytic core
42
What is the function of alpha subunits?
They can open and unfold the target protein by AAA ATPase and feed them into the B-subunit proteolytic core
43
3 of the B subunits in each rings are threonine proteases with 3 diff specialties. What are the specialties?
- Cleave on the carboxyl side of - > acidic - > basic - > or hydrophobic residues
44
What is another role that proteasomes play?
Immune surveillance. - invading pathogens make proteins that are destroyed by the proteasome - the peptides degraded by the proteasome are displayed on MHC (in the ER) then transported to the membrane and bound to the cell surface - immune cells can now recognize them
45
When humans are starved, have cancer, or are battling chronic diseases, muscle mass may need to be reduced and broken down my muscle proteins. This is done by the _________ system.
Ubiquitin/Proteasome System
46
What is velcade?
it's a drug for treating multiple myeloma
47
What does velcade do?
Blocks the proteasome, thus chokes tumor cells on misfolded proteins