When does lysosomal storage disease occur?
When lysosomal hydrolysis of particular macromolecules is defective so they accumulate. This results in enlarged lysosomes and impairement/destruction of cells.
True or false: most lysosomal storage diseases are autosomal dominant.
FALSE - they are single gene disorders and mostly autosomal recessive.
Define heterophagy and state three ways in which it may occur.
Heterophagy: digestion of material of extracellular origin. Can occur via phagocytosis, receptor-mediated endocytosis and pinocytosis/fluid-phase endocytosis.
Digestion of material of intracellular origin.
What is the structure of a lysosome? What do they contain and what is their pH?
Single membrane organelle found in cells. They have an acidic pH of 4.6 and contain enzymes that digest macromolecules.
What are the enzymes found in lysosomes?
Acid hydrolases including nucleases, proteases, glycosidases, lipases, phophatases and sulphatases.
Where are the enzymes sythesised and activated?
Synthesised in rER and activated in lysosome.
How is the lysosome protected from degradation?
Glycosylation of membrane proteins.
What is I cell disease?
Deficiency in N-acetylglucosamine phosphotransferase deficiency. Normally functions to phosphorylate mannose tags in cis golgi. Means that lysosome enzymes are secreted rather than directed to lysosome. Lysosome is engorged with undigested material.
What is the function of phagocytosis? Name three occasions it is used by cells.
internalise large particles. Used for nutrition, defence (macrophages and neutrophils) and removal of cellular debris and damaged cells.
Explain the 5 steps of phagocytosis.
1. Actin polymerisation and contraction when receptor binds.
2. Pseudopodia engulfs target. 3. Phagolysosome formed. 4. Sugars, aa, nucleotides (useful) enter cytosol. 5. Indigestible remnants expelled.
Name a pathogen that inhibits phagosome from fusing with lysosome.
Name a pathogen where bacteria are resistant to lysosomal enzymes and acid.
Name a pathogen where the pathogen damages the lysosome membrane and escapes back into cytosol.
Meningitis - listeria monocytogenes.
What is the function of receptor-mediated endocytosis?
Internalise solutes bound to a specific high affinity cell surface receptor.
What are the four things involved in receptor mediated endocytosis?
Adaptin, clathrin, dynamin and chaperones.
how is a ligand-receptor complex internalised in receptor mediated endocytosis?
Via a clathrin coated pit in the plasma membrane.
True or false: a clathrin lattice covers the cytosolic face of the coated pit.
What is the function of Adaptin in receptor mediated endocytosis?
Binds the cytosolic domain of the receptor and binds clathrin to ensure receptors are packaged and other integral proteins are not.
What is the main function of clathrin in receptor mediated endocytosis?
Assembly provides driving force for membrane curvature.
What is the function of dynamin in Receptor mediated endocytosis?
Uses energy from GTP to sever coated vesicle from membrane.
What is the function of chaperones in receptor mediated endocytosis?
Uncoat the vesicle.
Give two examples of receptor mediated endocytosis.
Transport of cholesterol in LDLs and transport or iron as transferrin.
What is an early endosome?
Endosome is what is made from receptor mediated endocytosis. Therefore an early endosome is the first thing that is made ish.
What is the function of the early endosome?
Site for sorting and recycling. It recycles receptors to the plasma membrane and the ligand goes to lysosomes e.g. LDL.
What difference is there in the action of endosomes in iron transport?
The ligand remains bound to the receptors in the form of apotransferrin therefore it doesnt go to the lysosome it goes back to the cell surface with the receptor.
True or false: viruses exploit receptor mediated endocytosis.
True - low pH causes conformational change in viral glycoprotein leading to exposure of hydrophobic region and the endosome membrane and viral envelope fuse.
What is taken in during pinocytosis?
Internalises extracellular fluid and dissolved particles.
What is cell rejuvination?
Removal of old or damaged organelles.
When is autophagy upregulated?
Steps in autophagy. Go.
1. target wrapped in double membrane from ER
2. Autophagosome produced
3. fuses with lysosome
4. indigestible remnants retained as granules that accumulate with age.
What is autolysis?
Release of lysosomal enzymes into the cytosol. Aids disposal of dead cells.
How does extracellular digestion occur? Give an example.
When the lysosome discharges its enzyme via exocytosis resulting in extracellular digestion. E.g. fertilisation - acrosome is a modified lysosome.
What is Tay-Sachs disease a deficiency in?
What is the normal function of B-N-acetylhexosaminidase? What is the result of this?
Degradation of ganglioside GM2, a major component of brain cell membranes. Results in undigested ganglioside GM2 in lysosomes of nervous tissue causing mental retardation, blindness, paralysis and death within 3 years.