Lysosomes Flashcards
What are endocytes?
Extracellular substrates
How are intracellular substrates transported?
- Microautophagy
2. Macroautophagy
Name some of the hydrolytic enzymes present within lysosomes
- proteases
- lipases
- glycosidases
- nucleases
- phosphatases
- sulphatases
What is the significance of receptor mediated endocytosis?
Uptake of LDL is the most important source of cholesterol to the body
Explain what microautophagy is
AKA ‘self eating’
invagination of the lysosomal membrane, moves inwards & pinches off inside the lysosome
How does the phagocytosis of erythrocytes occur?
- dead RBC engulfed by macrophage
- macrophage fuses with lysosomes
- pH drops - acidic conditions
- lysosomal hydrolytic enzymes degrade rbc
Outline how receptor mediated endocytosis occurs
- Molecules bind to LDL receptors
- Receptors move to coated pits and bind to LDL
- Cell membrane coated pits vaginate and pinch off becoming a vesicle
- pH drops - acidic conditions as vesicle fuses with endosomes
- Causing dissociation of LDL& molecules from receptors
- Vesicles transported to other part of cell to be used again
- LDL particles end up in lysosomes, receptors taken back to membrane
- Cholesterylester hydrolysed to produce cholesterol and fatty acids
What post translational modfications occur to lysosomal enzymes?
Mannose 6 modification via mannose 6 phosphate (M6P) pathway
How are the hydrolytic enzymes activated?
Via proteolytic cleavage
What are lipoproteins?
Complexes of lipids and proteins that carry fats through the bloodstream
e.g. HDL/LDL
Under what conditions are the hydrolytic enzymes activated?
An acididc environment is required for the acid hydrolases to work
How are lysosomal hydrolases produced in the ER lumen?
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
What is phagocytosis?
AKA ‘cell eating’
ingestion of bacteria and particles (0.5um) by phagocytes
Explain briefly what the mannose 6 phosphate pathway is
Major route for targeting lysosomal enzymes to the lysosomes
What is I cell disease?
Autosomal recessive disorder where all the hydrolases are missing from the lysosomes and are
present in the blood instead
What errors can occur in the post translational modifications of lysosomal enzymes?
Some lysosomal proteins can escape into the default pathway
M6P receptors are present in plasma membrane to bind escaped M6P proteins
What is macroautophagy?
Autophagsosomes (double membraned vesicles) made from chunks of cytosol or ER membranes
fuse with lysosomes to degrade their contents ultimately
What are the 2 ways substrates are extracellularly delivered ?
- phagocytosis
2. pinocytosis
Describe the structural features of lysosomes
- single membrane organelle
- Heterogenous contents (vesicles)
- Acidic (pH 4.5-5.0)
- 4-0 hydrolytic enzymes
What is autophagy?
Natural regulated physiological process of degrading non functional / unnecessary components in a cell
What is the fate of the lysosomal proteins produced in the ER?
Either end up in plasma membrane
Or in lysosomes via M6P pathway
What is the significance of macroautophagy?
Aids restructuring of differentiating cells
Provides adaptive responses to stresses such as starvation and infection
Outline the stages lysosomal enzymes take in the mannose 6 phosphate pathway
- once enzyme protein reaches transgolgi, M6P recognised by mannose 6 phosphate receptor
- Receptors bind to M6P concentrating it
- Proteins encoded that invaginate membrane to form vesicles containing M6P complex
- Vesicles specifically transported out to endosomes to lysosomes
How does I cell disease occur?
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
