L15

Question 1

what was believed about porteins before the 1940s

Answer 1

that we kept all of out proteins for our entire life’s but because of radioactive isotopes during the wars we learned that this was not the case

Question 2

how do lysosomes break down proteins

Answer 2

they break down the peptide bonds between amino acids

they can also break down nucleic acids and sugars

Question 3

describe the range in 1/2 life of proteins around the body

Answer 3

Protein stability (1/2 life) varies from a few minutes (e.g. cyclins which regulate mitosis) to a lifetime (proteins in the lens of the eye)

when proteins in the lense of our eye die you get cataracts .

Question 4

what does protein 1/2 life refer to

Answer 4

Protein half-life refers to an experimental measurement: The time that half of the original population of protein remains. Or the time that half of the original population of protein has been degraded.

Question 5

why are proteins degraded

theres 5

Answer 5

to regulate the function/activity of a protein and therefore the cell. E.g., ion
channels and transporters in epithelia to change ion transport pathways.

to allow replacement with new proteins.

to inactivate them e.g., ligands, cell cycle proteins.

to recycle amino acids of nonfunctional proteins e.g., misfolded or misassembled proteins in the ER.

as they are extracellular proteins from pathogens

Question 6

why do different proteins have different 1/2 lifes

Answer 6

Lifetime of a protein depends on the function of a protein and the cellular
pathway it is involved in.

Question 7

what degrades proteins

Answer 7

Degraded in the lysosome or the proteasome

Question 8

what do lysosomes break down

Answer 8

extracellular or transmembrane proteins brought into the cell by endocytosis and

aged or defective organelles (also called autophagy)

Question 9

what is autophagy

Answer 9

it is when a lysosome breaks down aged or defective organelles

Question 10

what does the lysosome contain

Answer 10

Contain enzymes (acid hydrolases) that work best at acidic pH (not in cytosol). The
enzymes break down
proteins, sugars and nucleic acids.

Question 11

what is the main enzyme that lysosomes contain

Answer 11

acid hydrolases

Question 12

how does the lysosome maintain its low pH

Answer 12

Two transport proteins pump H+ and Cl- into the lysosome

Question 13

what does autophagy mean

Answer 13

self eating

Question 14

describe the process of autophagy

Answer 14

Uptake of random area of cytoplasm or defective organelles (phagophore)

Phagophore forms a complete ‘vesicle’ (autophagosome)

Autophagosome begins to fuse with lysosome

Autolysosome formed, degradation begins

Organelles and any uptake substances degraded and recycled

Question 15

what is the difference between a phagophore, autophagosome and a autolysosome

Answer 15

phagophore = the beginning of engorgement and is the start of the formation of an autophagosome

an autophagosome is when the phagophore has completely engulfed the organelle in a continuous membrane

an autolysosome is when the autophagosome and lysosome come together and the contents of both mixes

Question 16

what is the difference between ubiquitin-proteasome system for protein degradation and autophagy

Answer 16

the ubiquitin system is highly controlled and not random like autophagy

Question 17

what are 4 things ubiquitin-proteasome system does

Answer 17

Highly controlled process for degrading unwanted proteins, terminating or activating signaling pathways, regulating the cell cycle and providing an important source of amino acids for de novo protein synthesis.

Proteins are covalently tagged with a small 8kDa protein called ubiquitin which then leads to them being degraded

Question 18

other than degradation, what else can ubiquitination lead to

Answer 18

endocytosis (monoubiquitin) or to change the location of a protein.

Question 19

in the ubiquitin-proteasome pathway, what is E1, E2, and E3

Answer 19

E1 (activating enzyme),

E2 (conjugating enzyme)

E3 (ligase)

Question 20

what is the role of E1, E2 and E3 in the ubiquitin-proteasome pathway

Answer 20

E1 catalyses the breakdown of ATP –> Amp which transfers ubiquitin onto the enzyme

E1 then transfers ubiquitin onto the E2 enzyme and then to the E3 enzyme

E3 then puts ubiquitin onto the protein

Question 21

what is needed to remove ubiquitin from a protein

Answer 21

Deubiquitinating enzymes or DUBs remove ubiquitin from

proteins.

Question 22

where are ubiquitinated proteins bound for

Answer 22

the protostome

Question 23

what is the process of how ubiquitin and the protostome degrade a protein

Answer 23

Ubiquitin binds proteasome and orients the protein at the regulatory particle so that the protein comes dont into the protostome (which is shaped like a cylinder)

the protein is then degraded in proteasome by
peptidase

Peptides and amino acids are recycled

Question 24

what is the protostome made up of

Answer 24

regulatory particle and a core particle

Question 25

how does ubiquitin tagging promote endocytosis of ion channels what are 2 examples of proteins regulated by this

Answer 25

1. ENaC and ROMK1 are monoubiquitinated, promoting endocytosis to the apical sorting endosome Ubiquitinated proteins trafficked onto common endosome where fate of the channel is determined Deubiquitination leads to recycling. Ubiquitinated proteins move on to lysosome for degradation through the late endosome

Question 26

what causes liddle's syndrome to occur

Answer 26

In Liddle’s syndrome (hypertension) ENaC cannot be tagged with ubiquitin due to loss of the binding site for an E3 ubiquitin ligase. Therefore less ENaC endocytosis, more ENaC at the plasma membrane and more Na+ reabsorption leading to high ECF volume and pressure

Question 27

what is monoubiquitination

Answer 27

a single addition of a ubiquitin to a protein

Question 28

what is multi-ubiquitination

Answer 28

a single ubiquitin at multiply sights on a protein

Question 29

what is polyubiquitination

Answer 29

a chain of ubiquitin attached to a single amino acid of a protein

Question 30

what part of the protein does ubiquitin bind to

Answer 30

Ubiquitin is covalently linked to lysines or to the N-terminal amino acid of the target/substrate protein.

Question 31

what are monoubiquitination and multi-ubiquitination signals for

Answer 31

These are signals | for endocytosis or movement through the endosome system.

Question 32

what is polyubiquitination a signal for

Answer 32

Chains of ubiquitin signal degradation of the target protein in the proteasome.

Question 33

what enzymes do Lysosome, Proteasome, and Autophagy contain

Answer 33

Lysosome = Acid hydrolases Proteasome = Peptidases Autophagy = Acid hydrolases

Question 34

what do Lysosome, Proteasome, and Autophagy degrade

Answer 34

Lysosome = proteins, sugars, DNA/RNA Proteasome = Proteins (ubiquitin recycled) Autophagy = Damaged organelles, microbes, cytosolic components

Question 35

describe the regulation of Lysosomes, Proteasomes, and Autophagy

Answer 35

Lysosome = Somewhat random, ubiquitin tagging Proteasome = Highly regulated Autophagy = Random, but some regulated

Question 36

what are the different cofactors between Lysosomes, Proteasomes, and Autophagy

Answer 36

Lysosome = no cofactors Proteasome = Requires a series of three enzymes: E1, E2 and E3 Autophagy = no cofactors

Question 37

what are the general targets of Lysosomes, Proteasomes, and Autophagy

Answer 37

Lysosome = Cell surface and extracellular proteins Proteasome = Cytoslic, nuclear, ER proteins (ERAD) Autophagy = Cytosolic components

Question 38

what is the structure of Autophagy

Answer 38

Autophagy = Double membraned | autophagosome

Question 39

Lysosomes only degrade proteins BECAUSE monoubiquitin is used as a tag for degradation in the endocytosis pathway

Answer 39

the first statment is false and the second is true the first statment is false because of the work only