Bevington 2 Flashcards
Enzymes which perform turnover
Proteases, lipases, Excision nucleases, RNAses etc.
Process of autophagy - organelle turnover
Membrane vesicles fuse and accumulate until an autophagosome englulfs an area of cytoplasm (including organelles). Double membrane - structure likely sourced from ER or mitochondria
Lysosome function
Contain digestive enzymes which aid in intracellular turnover or extracellular degradation of components before endocytosis
Examples of protein turnover
- In organelles, eg lysosomal and autophagosomal proteases (low pH)
- In cytosol, e.g
- Calcium activated cytosolic proteases (calpains) ~pH7
- The Ubiquitin proteosome pathway
Ubiquitin proteosome pathway
- structures and function of molecules involved
Ubiquitin - small protein which marks proteins for degradation via covalently bonding with them
Proteasomes - huge macromolecular complex containing unfoldases and proteases which target polyubiquitinated proteins
Process requires ATP
Why is is necessary for molecules to be turned over?
1) Control the time course of gene expression -mRNA halflife much shorter than that of proteins, allowing transient expression of genes
2) Proteins may ‘mis-fold’, leading to harmful aggregates
3) Cumulative damage to molecules - Reactive oxygen species (ROS) can cause damage, resulting in loss/gain of function
Some oxidised molecules are not replaced, e.g. oxidised lipids in atheroscelrosis - explain
accumulation of partly oxidised Low Density Lipoprotein (LDL) in the walls of blood vessels can lead to Atherosclerosis, causes plaques, thrombosis, ‘fatty streaks’
3 ways deoxynucleotides can be damaged?
- Oxidation by ROS e.g. -OH attack
- Hydrolysis
- Methylation
Outline a mechanism of DNA repair
Nucleotide excision repair
- Excision nuclease makes cut on damaged area(usually pyrimidine dimers)
- DNA Pol I fills in resulting gap
- DNA ligase seals strand
