Intracellular Proteolysis

Question 1

what doe proteinases, peptidases and cathepsins all have in common?

Answer 1

they are all proteases

Question 2

what are cathepsins?

Answer 2

lysosomal enzymes

Question 3

why do proteases in the small intestine need to be non specific?

Answer 3

so they can degrade any type of protein ingested

Question 4

what are the 2 types of proteolysis?

Answer 4

specific and non specific

• specific leads to the activation of proteins
• eg insulin

-non specific leads to protein degradation
eg small instestine

Question 5

what are someone prominent proteases?

Answer 5

1) factor IX (on X chromosome)
- factor in the clotting cascade

2) bromelain + papain
- meat tenderiser

3) HIV-1 protease

Question 6

what are the 2 pathways for protein degradation?

Answer 6

lysosomal degradation and the ubiquitylation proteasome pathway

Question 7

what are ubiquitins?

Answer 7

small regulatory proteins that are attached covalently to the substrate protein.

Question 8

what is a proteasome?

Answer 8

a large protease complex the active sites all point towards the center of the inner cavity.

Question 9

describe the ubiquitylation pathway

Answer 9

• ACTIVATION: ubiquitin attaches to cysteine residue of the ubiquitin activating enzyme E1 at C terminus w thioester bond
• CONJUNCTION: ubiquitin release cysteine and attaches to ubiquitin conjugating enzyme E2
• LIGATION: transfer of ubiquitin from E2 to a lysine in the target protein, or to the other ubiquitin molecules already attached to a target (polyubiquitination)

Question 10

which type of aa have a short half life?

Answer 10

destabilising

Ile, Gln, Tyr, Pro, Glu

Question 11

which stabilising aa have a long half life?

Answer 11

Met, Gly, Ala, Ser, Thr, Nal

Question 12

what is the N end rule?

Answer 12

E3 ubiquitin ligases have poor affinity for stabilising a- terminal

Question 13

why is the liver the only organ that can get rid of cholesterol completely?

Answer 13

it can convert cholesterol into bile acids

Question 14

how do statins work?

Answer 14

-block cholesterol biosynthesis

Question 15

how do we classify proteases based on the manner in which they bind to and cleave their targets?

Answer 15

• ENDOPEPTIDASES: they break peptide bonds of non-terminal amino acids (ie. within the molecule)
• EXOPEPTIDASES: they break peptide bonds of terminal amino acids (ie. cleaves at the end of a polypeptide chain)

Question 16

what are the two subdivisions of exopeptidases?

Answer 16

• AMINOPEPTIDASES: cleaves peptide bonds at the N-terminal (amine terminus)
• CARBOXYPEPTIDASES: cleave peptide bonds at the C-terminal (carboxy terminus)