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Lysosome Degradation

Lysosomes, Protein Turnover and Peroxisomes

QuestionAnswer
Name key features of the lysosome Has a battery of hydrolases, about 50-60 hydrolases that are capable of degrading polymeric structures
True or False: Lysosome cannot remove modifications False. They remove modifications and take off phosphate groups
What can nucleases degrade? Proteases? Nucleases: Degrade DNA and RNA into bases. Proteases: Degrade proteins into amino acids
What pH do nucleases and proteases operate at? Acidic pH around 5-6
What is the pH in the cytoplasm? 7.2
Why is the interior of lysosome maintained at an acidic pH? Because of the active pumping of hydrogen ions at the expense of ATP hydrolysis
What do acid phosphatase remove? Phosphate groups from proteins
Where are the hydrolases of the lysosome originally translated? In the RER by standard pathways
Where does N-linked glycosylation occur? In the ER
What are hydrolases glycosylated with? A mannose sugar from RER and transferred to cis golgi
Describe the modification of the mannose sugar on hydrolases Phosphotransferase puts a precursor sugar on then there is a trimming reaciton and M6P is end product
What are M6P receptors recognized by? By specific M6P receptors and they cluster in a region
What do the region of M6P gets coated with? Clathrin coat
What does the coating of clathrin cause? Results in the pinching off of the coat
After the vesicle loses its clathrin coat what happens? It goes to the endolysosome
Describe LAMP proteins Classic ER-Golgi pathway. Hydrolases within many tissues may have specific tag mechanism whereby there are delivered to the interior
What are macrophages? Specialized for phagocytosis
Describe how complements can play a role in phagocytosis May coat a bacteria and have it specifically recognized by receptors and internalized for cells specific for phagocytosis
Describe pinocytosis Invagination of the plasma membrane. Means drinking of the extracellular fluid (Particle is not concentrated after being taken up)
Other endocytosis process are more complex because vesicles can take on tubular shapes and more changes. Describe pH gets more acidic as they go from plasma membrane becoming more mature lysosomes
Can the more complex endocytosis be mediated? Yes. It can be receptor mediated so that ligand can bind to specific receptors. Receptors can concentrate what is being taken in
Describe autophagy Internal contents of the cell are enclosed by a membrane and will become a lysosome by vesicular fushion
Described receptor-mediated endocytosis A ligand outside binds to receptors and is coated by clathrin. Pinching off of pit and removal of clathrin. Maturation process called elongation
Study that lead to receptor mediated endocytosis being worke out Hypercholesterolemia: Pre-mature aging and defects in LDL receptors
Describe microautophagy Lysosome can undego internalization of membrane. Take in some cellular components consitutively which results in degradation of intracellular soulble proteins
Describe Macroautophagy Resuls in degadation of organelles like mitochondria and vacuoles that form from SER. Forms autophagic vacuoles
Describe Direct Protein transfer Direct uptake of proteins by macroautophagiv vacuoles
What induces macroautophagy and direct protein transfer? Nutritional starvation
How is it possible that receptors get degraded along with ligands? Ubiquitin can cause internalization of the membrane so the receptor is trapped inter-lumenal instead of recycled to PM
True or False: Direct protein uptake is chaperone mediated True. Certain proteins have specific amino acid sequence (signal)
True or False: During starvation Direct protein uptake kicks in before macroautophagy False macroautophay kicks in first then direct protein uptake kicks in for selectivity and can extend for a long period of time
Describe lysosomal storage disease One particular hydrolase is defective or not expressed at all. Accumulation of products in lysosome. (can be fatal)
Example of lysosomal storage disease Tay-Sachs disease (genetic). Develops from absence of Hexosaminidase A. Accumulation of gangliosids
Describe the UB-Proteasome system ATP dependent. Important for tagging proteins that are going to be degraded. Proteasome unwinds the protein so it can fit (Like garbage disposal)
True or False: Proteins can be degraded only after translation False. Can be degraded during translation or after
Describe Peroxisomes Produces hydrogen peroxide. Creates fatty acids and alcohol metabolism. Contribute to cholesterol metabolism. Make myelin
What is the role of peroxisomal catalase Breaks peroxide down to water
What is Adrino Leuko Deficiency Rare disease that results from insufficient myelin synthesis
True or False: Peroxisomes are from classic ER-Golgi False. Thought the membrane may bud off of the ER
Where are most proteins of peroxisomes made? In the cyotsol then translated then imported into peroxisome (signal sequence regulated)
What is the 3 amino acid C-terminus of peroximal proteins? Site that is recognized by a specific transport protein and channels for uptake
Waht is Zellwaggers Syndrome Defect in receptor that recognizes C-terminal tripeptides. Don't get peroxisomes that are properly incorporating their proteins. Can be fatal