14. Lysosomes

Question 1

Describe the 5 properties of Lysosomes? (5pts)

Answer 1

1. 100 Lysosomes per cell
2. Single membrane
3. 40 Hydrolytic enzymes- enzymes that catalyse reactions that break covalent bonds by utilising water.
4. Lysosomes only work at a low PH of 4-5
5. Heterogenous contents

Question 2

Give 6 examples of the 40 hydrolytic enzymes (6pts)

Answer 2

1. Lipases- hydrolyse lipids
2. Glyccosidases- hydrolyse carbohydrates
3. Proteases- hydrolyse proteins and peptides
4. Nucleases- hydrolyse nucleic acids
5. Phosphatase’s- hydrolyse phosphate groups
6. Sulfatases- hydrolyse sulphate groups

Question 3

Describe the structure of Lysosomes (12pts)

Answer 3

1. Lysosomes contain a lot of hydrolyses in their lumen which are soluble enzymes.
2. Lysosomes contain a high proteins concentration which gives them a low PH.
3. Lysosomes contain organelle proteins such as v-APTASE which sits in the lysosome membrane and pumps protons into the lumen of the lysosome.
4. Lysosome requires ion channels and transporters
5. The breakdown of Lipids produces cholesterol which is then transported by cholesterol transporters.
6. The breakdown of carbohydrates by glycosides produces monosaccharides which leaves the lysosomes through membrane embedded sugar transporters. The released cholesterol is then used for membrane biogenesis.
7. Nucleases break down RNA and DNA that produces nucleosides.
8. Proteases break down peptides and proteins to amino acids which need to be released through amino acid transporters.
9. Lysosomes constantly exchange materials with other organelles within the secretory pathway system through processes including vascular budding and fusion
10. Lysosomes have proteins on their membranes such as small GTPases and snares which are responsible for the final fusion step in the vesicle targeting process.
11. Lysosomes move in the cell along the microtubules which require certain adapters that attach to the microtubules
12. The surface of lysosomes include signalling complexes involved in metabolic signalling, immune responses and transcription factors.

Question 4

Describe Melanosomes ( 2pts)

Answer 4

1. Produced by melanocytes and transferred to keratinises in the skin.
2. Contain high concentrations of melanin which absorb UV light therefore protects us from the damaging effect of sunlight.

Question 5

Describe Lysosomal substrates (2pts)

Answer 5

There are 2 types of substrates that are delivered to lysosomes:

1. There are extracellular substrates which enter the cell through endocytosis.
2. There are intracellular substrates which are delivered to the lysosomes.

Question 6

Describe extracellular substrates? (2pts)

Answer 6

Extracellular substrates enter the cell through endocytosis:

1. Fluid-phase endocytosis of molecules and lipoproteins- e.g receptor-mediated endocytosis.
2. Phagocytosis of particles- is the uptake of particles larger than 0.5 micrometers.

Question 7

Describe receptor mediated endocytosis (1pts)

Answer 7

When substrates attach to receptors on the surface of the membrane. e.g how cholesterol crosses the plasma membrane.

Question 8

Describe how cholesterol passes the plasma membrane in receptor mediated endocytosis? (4pts)

Answer 8

LDL= Particles that carry a lot of cholesterol and triglycerides (bad cholesterol)

1. LDL’s bind to its receptor on plasma membranes where the membrane invaginate and clusters molecules in coated pits.
2. Once inside the cell, the ph decreases causing the dissociation of receptor and LDL molecule.
3. Receptor is then transported back to the cell surface to repeat the cycle.
4. LDL particles transported to lysosomes via early and late endosomes.

Question 9

Describe Phagocytosis (4pts)

Answer 9

1. Particle interacts with the cell surface and is pulled inside to form a phagosome
2. Phagosome fuses with the lysosome to form a phagolysosome.
3. Proton pumps that sit on the lysosomal membrane that pumps protons from inside of the lysosome decreases Ph which is essential for the activity of enzymes
4. Digestion breaks all contents to small metabolic building blocks and is reused by the cell.

Question 10

Describe the phagocytosis of red blood cells (2pts)

Answer 10

As red blood cells age they loose their flattened shape and become round

1. Red blood cells make contact with the macrophage
2. Macrophage engulfs pathogen

Question 11

Describe intracellular substrates (3pts)

Answer 11

Intracellular substrates are delivered to the lysosome:

1. Microutophagy- invagination of the lysosomal membrane.
2. Macroautophagy- cytosol or organelles wrapped in er fuses with lysosomes
3. Selective transport of proteins across the lysosomal membrane.

Question 12

Name the 5 viruses that emerge from endosomes? (5pts)

Answer 12

1. HIV
2. Infleunza
3. Poliovirus
4. Adenovrius
5. Sars covid

Question 13

Describe HIV?

Answer 13

HIV binds to the cell surface of the plasma membrane and delivers its contents leading to infection

Question 14

Describe Influenza (3pts)

Answer 14

1. Influenza virus is taken up by endocytosis in endosomes
2. The drop in PH causes the activation of viral proteins that mediate the fusion off the viral membrane of the endosomal membrane.
3. This leads to the release of the viral contents and infection.
   - influenza virus has a lipid bilayer

Question 15

Describe Poliovrius (3pts)

Answer 15

1. Has a capsid
2. Taken up by endocytosis
3. Once it reaches endosomes and its low PH it activates mechanisms for injection of the viral genome to the ctytoplasm.

Question 16

Describe the Adenovirus (2pts)

Answer 16

1. Capsid virus taken up by endocytosis
2. The entire viral particle is delivered to the cytoplasm and is docked onto the nuclear pore complexes to deliver its genome.

Question 17

Describe protein Glycosylation in the ER? (3pts)

Answer 17

1. Protein is synthesised and enters the lumen of the ER.
2. The large carbohydrate structure is transferred onto the protein specifically on a aspagrine residue.
3. All lysosomal hydrolyses receive these saccharide which are then mollified in a series of steps.

Question 18

Describe the Mannose 6-Phosphate pathway? (3pts)

Answer 18

1. The specialised digestive enzymes and membrane proteins of the lysosomes are synthesised in the ER and transported through the Golgi apparatus to the trans Golgi network.
2. While in the ER and cis golgi network the enzymes are tagged with mannose-6 phosphate. When they arrive in the trans golgi network they are recognised by mannose-6 phosphate receptors.
3. The tagging permits the enzymes to be sorted and packaged into transport vesciles which bud off and deliver their contents to the lysosome via late endosomes.

Question 19

Describe the I-cell disease

Answer 19

1. Defects in enzyme that produces the mannose-6 Phosphate tag.
2. These enzymes are not phosphorylated and so wont be recognised by mannose-6 phosphate receptors and so are not targeted to the lysosome.
3. This means they are being made, transported to the ER and golgi like normal but since it is not recognized by a receptor they take the default pathway and are secreted from the cell and end up in extracellular space.

Question 20

How do lysosomes appear in electron micrographs? (1pts)

Answer 20

Appear dark because they are filled with undigested biological material

Question 21

Describe the side effects of I-cell disease (6pts)

Answer 21

1. Skeletal abnormalities
2. Development delay
3. Enlarged liver and spleen
4. Impaired hearing
5. Death from pneumonia
6. Caused by enzyme affected by an Autosomal-recessive disorder.

Question 22

How is the outer membrane of lysosomes protected from degradation?

Answer 22

The outer membrane is embedded with specific membrane proteins which are heavily modified by polysaccharides. Many proteins are glycosylated and so lysosomes have polysaccharide groups attached to prevent luminal enzymes from reaching and degrading.