Lysosomes

Question 1

Where are lysosomes made?

Answer 1

→in the ER

Question 2

What is the pH inside a lysosome

Answer 2

→4-5

Question 3

why is the pH acidic inside a lysosome?

Answer 3

→enzymes need a low pH

→if the lysosome were to break the hydrolytic enzymes would be neutralized in the cytosol

Question 4

how does the lysosome maintain the acidic pH ?

Answer 4

→hydrogen ion pump which requires ATP

→active transport of H+ ions from the cytoplasm

Question 5

What are the two ways that substrates enter the lysosome?

Answer 5

→extracellular - endocytosis

→intracellular - microautophagy

Question 6

How does LDL get into the lysosome?

Answer 6

→binds to LDL surface receptors

→receptors aggregate to form coated pits

→the pit folds inwards and the membrane detaches itself to form a closed coated vesicle.

→pH starts to drop so LDL is inside an endosome and the receptors return to the cell surface membrane.

Question 7

what is LDL hydrolyzed into?

Answer 7

cholesteryl ester and fatty acid by lipase enzymes.

Question 8

What modification do lysosomal enzymes have that others don’t?

Answer 8

mannose-6-phosphate

Question 9

what is the name of the enzyme that adds the M6P modification?

Answer 9

phosphoryl transferase

Question 10

Where do proteins that do not have the M6P modifications go?

Answer 10

the plasma membrane

Question 11

what happens if there is no M6P modification?

Answer 11

The enzyme gets diverted and is secreted, substrate builds up inside the lysosome.

Question 12

Describe the structure and function of lysosomes

Answer 12

→Cells contain over 100 individual lysosomes

→ each lysosome is surrounded by a single membrane

→ Lysosomal interior is acidic (pH 4-5)

→Lysosomes contain over 40 hydrolytic enzymes capable of degrading: lipids (lipases), carbohydrates (glycosidases), proteins (proteases)

→Carry out the controlled intracellular digestion of both extracellular materials & worn-out organelles

Question 13

Describe substrate delivery to lysosomes

Answer 13

EXTRACELLULAR SUBSTRATES:
→ Fluid-phase endocytosis of molecules & lipoproteins

→Phagocytosis of particles ≥0.5 μm

INTRACELLULAR SUBSTRATES;
→Microautophagy (invagination of the lysosomal membrane)
→Macroautophagy (where the cytosol or organelles are wrapped in ER membrane, then fused with the lysosomes)
→Selective transport of proteins across the lysosomal membrane.

Question 14

Describe the mannose 6-phosphate (M6P) pathway

Answer 14

→ digestive enzymes & membrane proteins of the lysosome are synthesised in the ER & transported through the Golgi apparatus to the trans-Golgi network.

→While in the ER & cis-Golgi network, the enzymes are tagged with a specific phosphorylated sugar group (mannose 6-phosphate).

→When they arrive in the trans-Golgi network they can be recognized by an appropriate receptor, the mannose 6-phosphate receptor.

→The tagging permits the enzymes to be sorted & packaged into transport vesicles, which bud off & deliver their contents to the lysosome via late endosomes.

Question 15

Describe I-Cell disease and some symptoms

Answer 15

→It results from a defective phosphotransferase (GlcNAC).

Some of the symptoms are: 
→skeletal abnormalities 
→ development delay 
→ enlarged liver & spleen 
→ impaired hearing 
→ death from pneumonia or congestive heart failure, usually within the first 10 years.

Question 16

How does I - Cell Disease Occur?

Answer 16

1. Due to defective or missing GlcNAc phosphotransferase.
2. Lysosomal enzymes are not phosphorylated in the cis Golgi network.
3. The M6P receptors do not segregate them into the appropriate transport vesicles in the TGN.
4. Instead, the lysosomal hydrolases are carried to the cell surface and secreted.
5. No hydrolases in lysosomes = accumulation of undigested substrates in lysosomes.