L7 - Intracellular proteolysis

Question 1

why is protein degredation essential for metabolism

Answer 1

removes damaged or misfolded proteins caused by oxidation, errors etc

prevents toxic aggregation in cells

Question 2

what proscess increase intracellular protein degredation

Answer 2

starvation - cells break down proteins to reccyle nutrients

apoptosis - caspases degrade cellular proteins

stress - increase misfolded targets for degredation

Question 3

what are the basics of nucleophillic attack

Answer 3

proteases hydrolyse peptide bonds using nucleophile

• attack carbonyl carbon in peptide bond

= chymotryspsin uses a serine-histidine-aspartate traid to create a reactive oxygen atom for attack

Question 4

what are the 4 main mammilian protease families

Answer 4

serine

cysteine

asparrtic

metalloproteases

1 extra: proteosome is the only threoni ne protease = ubiquitin mediated

Question 5

why is ATP required for intracellular degredation

Answer 5

ubiquitin (not lysosomal) tagging requires ATP

proteasome activity uses ATP to unfold and transolcate proteins into core

lysosomal autophagy involves vesicle formation + transport = btoth need ATP

Question 6

hwo are acid hydrolases transported to the lysosome

Answer 6

1. Acid hydrolases tagged with mannose-6-phosphate (M6P) in golgi
2. tagged enzymes bind to M6P receptors in TGN
3. transported via clathrin-mediated vesicles to lysosome
4. at low pH in lysosome -> enzyme disocciates from recepor

Question 7

how are substrates tagged for lysosome delivery

Answer 7

1. endocytosis = enguld external proteins or particles
2. Autophagy = wrap organelles or proteins in a membrane for delivery
3. phagocytosis = enguld large particles via immune cells
4. chaperone-mediated autophagy = specific proteins recognised by chaperones and directly shuttled into lysosome

Question 8

lysosomal storage diseases

Answer 8

caused by defects in lysosomal enzymes or their transport

Question 9

what happens in I-cell disease (mucolipidosis 2) that causes lysosomal storage disease

Answer 9

1. eznymes LACK M6P tags –> dont reach lysosome
2. substrates build up = inclusion bodies form inside cells

= impaired degredation of cellular waste –> tissue damage