Lysosomes

Question 1

What are lysosomes created from?

Answer 1

Endosomes and vesicles from the golgi apparatus

Question 2

How is an endosome formed?

Answer 2

The plasma membrane will form a endocytic vesicle via endocytosis, and will contain cargo that will overtime become more acidic (due to the pumps present on its membrane)- the more acidic it becomes, the mature the endosome considers to have become.
NOTE: in mature endosomes, the phosphate is removed from the mannoses on the hydrolases which ensures that the hydrolases do not return to the golgi apparatus with the receptor.

Question 3

Where are digestive enzymes formed?

Answer 3

They are formed by ribosomes on the RER membrane and becomes packaged in the golgi apparatus.

Question 4

What are all digestive enzymes labelled in? What does it do?

Answer 4

They are all labelled in a mannose-6-phosphate tag via modification of sugars that were attached to the endosome in the ER (glycosylation), which tells the golgi apparatus that the digestive enzymes are going to a specific type of vesicle.

Question 5

Where does the digestive enzymes get the mannose-6-phosphate tag? What happens to it?

Answer 5

It gets tagged within the golgi apparatus and when the digestive enzymes reach the trans face, the M6P receptors present will interact with the tag which will make sure that its the enzymes are going to the right vesicle. After this is done, it will then bud off to form a lysosome.

Question 6

How does a lysosome form from a mature endosome?

Answer 6

The mature endosome will fuse with a lysosomal vesicle which help the new lysosome form into a mature lysosome- when the fusion occurs, the enviroment will become acidic enough to allow for the dissociation of the digestive enzymes (formed in the endosome) from the M6P receptors found on the membrane of the golgi, which will activate them by interacting with a clarathin coat.
Once the enzymes have been activated, the lysosomes and the activated enzymes will bud off from the endosome, creating a full lysosome which is ready to be used in the cell or transported outside the cell.
The M6P receptors can be recycled.

Question 7

Why are the digestive enzymes of the lysosomes known as acidic hydrolases?

Answer 7

Due to the digestive enzymes needing an acidic enviroment to be activated and make them work efficiently.

Question 8

How does the lysosome maintain its acidic enviroment?

Answer 8

It contains H+ ATPase pumps within the membrane.

Question 9

What is the pH value within the lysosome and why?

Answer 9

It is around 5 and its is that level to act as a safety mechanism- if the lysosome bursts, it will release its contents, the acidic hydrolases, in the cytoplasm which can digest them, however, they will not be able to do so in small amounts as the pH of the cytoplasm is around 7.4, so if any gets released in the cytosol, it will remain unaffected.
HOWEVER if many lysosomes burst at one time, it could cause the pH to lower and activate the enzymes, which can cause the organelles to become digested.

Question 10

What do transporters do?

Answer 10

They transport products, that the lysosomes create after digestion, such as amino acids, sugars and nucleotides to the cystols for them to get utilised.

Question 11

What are a few features of a lysosome?

Answer 11

• there are around 100 lysosomes so are more abundant than the golgi apparatus.
• have a single membrane bilayer- most of the lysosomal membrane proteins are very glycosylated which helps protect the membrane from lysosomal proteases in the lumen.
• acidic inside (pH around 4-5), membrane proteins pump protons from the cytosol into the lysosome
• contains different substances inside- different enzymes.

Question 12

How many different acidic hydrolases that can carry out digestive processes are found within the lysosome?

Answer 12

There are 40 hydrolytic enzymes-

• proteases- digest proteins
• lipases- digest lipids
• glycosidase- break down sugars or polysaccharides
• nucleases- break down DNA and RNA
• phosphatase- cleaves off phosphate groups
• sulfatases- cleaves off sulphate groups

Question 13

How are extracellular substrates delivered to lysosomes?

Answer 13

• endocytosis- fluid-phase endocytosis of small molecules and lipoproteins (it includes receptor-mediated endocytosis).
• Phagocytosis of particles that are smaller than 0.5um in diameter such as bacteria, fungi or dead cells, forming phagosome.

Question 14

How are intracellular substrates delivered to lysosomes?

Answer 14

• microautophagy
• macroautophagy
• selective transport
• fluid-phase endocytosis
• Phagocytosis
• Autophagy

Question 15

What is microautophagy?

Answer 15

-microautophagy- self-eating, the invagination of the lysosomal membrane to form a vesicle that will then be digested by intracellular enzymes.

Question 16

What is macroautophagy?

Answer 16

• macroautophagy- bits of cytosol or organelles that become wrapped in the ER membrane and then fuses with the ER membrane, to be digested by the enzymes.
• autophagosome is created, creating a double membrane.
• everything other than the outer bilayer of the autophagosome will be degraded once they fuse with the lysosomes.

Question 17

What is selective transport of proteins?

Answer 17

-selective transport of the proteins across the lysosomal membrane (there might be a specific transporter which recognises specific signals and transfers the proteins across the lysosomal membrane)

Question 18

What is fluid-phase endocytosis?

Answer 18

-fluid-phase endocytosis molecules taken by being dissolved in medium or binding to cell surface receptors. As they are being transported, the pH decreases at each stage, and when at low enough, the acidic hydrolases will become activated.

Question 19

What is phagocytosis?

Answer 19

-Phagocytosis- where a phagocyte engulfs a bacteria and the phagocytic vacuole will fuse with a lysosome to form a phagosome, which then digests the bacteria.

Question 20

What is autography?

Answer 20

-Autophagy- this is where the cellular membrane of the lysosome or something else envelops a mitochondria and forms a autophagosome to then degrade the mitochondria.

Question 21

How does receptor-mediated endocytosis work?

Answer 21

• Particles are selectively taken to be delivered to the lysosome for digestion
• There are receptors on the membrane that are complementary to the extracellular substrate that needs to be digested
• Substrate binds to receptor
• Membrane invaginates to form a coated pit and then a vesicle around the substrate
• Receptors are recycled and put back on the plasma membrane
• example of fluid-phase endocytosis

Question 22

Give an example of receptor-mediated endocytosis.

Answer 22

• LDL= low density lipid which is known as bad cholesterol and can cause atheroma formation to increase if present in large amounts, therefore increasing the risk of a heart attack.
• LDL particle is a major source of cholesterol for cells but also contains protein and phospholipid monolayer- need for things such as the plasma membrane.
• LDL binds to the LDL receptor on the plasma membrane
• They cluster in patches of membrane called coated pits
• They can then invaginate to form vesicles, which insides can lower the pH
• The lower pH can cause the receptors to dissociate from the LDL particle
• These receptors can then recycle back to the plasma membrane, while the LDL are then transported for the the lysosomes.
• In the LDL, the cholesteryl ester is hydrolysed to form fatty acid and cholesterol.
• The cholesterol can be used to synthesise new membranes, and the fatty acid and amino can be used to form triglycerides and proteins.

Question 23

What is lysosomal storage disease?

Answer 23

Lysosomal storage disease (LSD) is caused by genetic defects in humans, and affects one or more of the hydrolases and causes accumulation of their undigested substrates in the lysosomes, which can cause severe pathological consequences. There is a number of lysosomal storage disorders.

Question 24

What is Pseudo-Hurler polydystrophy (mucolipidosis type III)/ Hurler’s disease?

Answer 24

It is a type of lysosomal storage disease (autosomal recessive neurodegenerative disorder) which is caused when the GNPTG gene is mutated so less GlcNAc-phosphotransferase is created, an enzyme which is used to synthesis the mannose-6-phosphate chain, which means that the lysosome will not be able to be packaged into vesicles correctly so no phosphorylation and glycosylation of enzyme which means that the enzymes are secreted.
This can cause a series of symptoms such as:
-Skeletal problems
-Growth problems
-Heart problems
-Pneumonia
-Enlarged liver