Lysosomes

Question 1

What are endocytes?

Answer 1

Extracellular substrates

Question 2

How are intracellular substrates transported?

Answer 2

1. Microautophagy

2. Macroautophagy

Question 3

Name some of the hydrolytic enzymes present within lysosomes

Answer 3

• proteases
• lipases
• glycosidases
• nucleases
• phosphatases
• sulphatases

Question 4

What is the significance of receptor mediated endocytosis?

Answer 4

Uptake of LDL is the most important source of cholesterol to the body

Question 5

Explain what microautophagy is

Answer 5

AKA ‘self eating’

invagination of the lysosomal membrane, moves inwards & pinches off inside the lysosome

Question 6

How does the phagocytosis of erythrocytes occur?

Answer 6

1. dead RBC engulfed by macrophage
2. macrophage fuses with lysosomes
3. pH drops - acidic conditions
4. lysosomal hydrolytic enzymes degrade rbc

Question 7

Outline how receptor mediated endocytosis occurs

Answer 7

1. Molecules bind to LDL receptors
2. Receptors move to coated pits and bind to LDL
3. Cell membrane coated pits vaginate and pinch off becoming a vesicle
4. pH drops - acidic conditions as vesicle fuses with endosomes
5. Causing dissociation of LDL& molecules from receptors
6. Vesicles transported to other part of cell to be used again
7. LDL particles end up in lysosomes, receptors taken back to membrane
8. Cholesterylester hydrolysed to produce cholesterol and fatty acids

Question 8

What post translational modfications occur to lysosomal enzymes?

Answer 8

Mannose 6 modification via mannose 6 phosphate (M6P) pathway

Question 9

How are the hydrolytic enzymes activated?

Answer 9

Via proteolytic cleavage

Question 10

What are lipoproteins?

Answer 10

Complexes of lipids and proteins that carry fats through the bloodstream
e.g. HDL/LDL

Question 11

Under what conditions are the hydrolytic enzymes activated?

Answer 11

An acididc environment is required for the acid hydrolases to work

Question 12

How are lysosomal hydrolases produced in the ER lumen?

Answer 12

Lysosomal proteins produced via transcription
Complex sugar structure transferred from one big chunk in membrane anchor to lysosomal proteins
Signal peptide cleaved off
Lysosomal hydrolase transported to golgi for post translational modifications

Question 13

What is phagocytosis?

Answer 13

AKA ‘cell eating’

ingestion of bacteria and particles (0.5um) by phagocytes

Question 14

Explain briefly what the mannose 6 phosphate pathway is

Answer 14

Major route for targeting lysosomal enzymes to the lysosomes

Question 15

What is I cell disease?

Answer 15

Autosomal recessive disorder where all the hydrolases are missing from the lysosomes and are
present in the blood instead

Question 16

What errors can occur in the post translational modifications of lysosomal enzymes?

Answer 16

Some lysosomal proteins can escape into the default pathway

M6P receptors are present in plasma membrane to bind escaped M6P proteins

Question 17

What is macroautophagy?

Answer 17

Autophagsosomes (double membraned vesicles) made from chunks of cytosol or ER membranes
fuse with lysosomes to degrade their contents ultimately

Question 18

What are the 2 ways substrates are extracellularly delivered ?

Answer 18

1. phagocytosis

2. pinocytosis

Question 19

Describe the structural features of lysosomes

Answer 19

• single membrane organelle
• Heterogenous contents (vesicles)
• Acidic (pH 4.5-5.0)
• 4-0 hydrolytic enzymes

Question 20

What is autophagy?

Answer 20

Natural regulated physiological process of degrading non functional / unnecessary components in a cell

Question 21

What is the fate of the lysosomal proteins produced in the ER?

Answer 21

Either end up in plasma membrane

Or in lysosomes via M6P pathway

Question 22

What is the significance of macroautophagy?

Answer 22

Aids restructuring of differentiating cells

Provides adaptive responses to stresses such as starvation and infection

Question 23

Outline the stages lysosomal enzymes take in the mannose 6 phosphate pathway

Answer 23

1. once enzyme protein reaches transgolgi, M6P recognised by mannose 6 phosphate receptor
2. Receptors bind to M6P concentrating it
3. Proteins encoded that invaginate membrane to form vesicles containing M6P complex
4. Vesicles specifically transported out to endosomes to lysosomes

Question 24

How does I cell disease occur?

Answer 24

Golgi sorting failure due to defective GlcNAc phosphotransferase
- hydrolases are secreted rather than transported to lysosomes
so
- Lysosomal enzymes not phosphorylated in golgi
- Not segregated by M6P into vesicles
- so are carried to cell surface and secreted

Question 25

Which process are pinocytosis and phagocytosis examples of?

Answer 25

Endocytosis

Question 26

Approximately how many lysosomes are there per cell?

Answer 26

~ 100

Question 27

What are the symptoms of I cell disease?

Answer 27

``` Skeletal abnormalities Developmental delay Death by pneumonia, heart failure at young age (10yrs) Enlarged liver and spleen Impaired hearing ```

Question 28

What can be removed from cells via Autophagy?

Answer 28

Large molecules (macromolecules) Large protein aggregates Whole organelles

Question 29

What is meant by pinocytosis?

Answer 29

AKA 'cell drinking' | fluid endocytosis - ingestion of liquid into the cell by forming small vesicles from the membrane