AB4: Turnover Flashcards
What is turnover?
continuous degradation of the molecules and cells, matched by synthesis and renewal of those molecules and cells
What are the 2 concepts of turnover?
1.Turnover of components within cells
Molecules and organelles undergo degradation to precursor molecules and waste products (e.g. proteins to amino acids)
Some of these precursor molecules are the used to renewal these molecules by biosynthesis and reform these molecules
Occurs particularly in eukaryotes
2.Turnover of cells
Cells die via apoptosis or necrosis and are broken down into their precursor molecules and waste products
Precursor molecules are use as nutrients by the surviving cells to undergo renewal and form new cells
What enzymes carry out turnover?
- Protein degradation is carried out by protease enzymes
- RNA degradation is carried out by RNAse enzymes
- DNA turnover (repair) is carried out by excision nucleases
- Lipid degradation is carried out by lipases
What cellular compartments carry out turnover?
cytosol, lysosomes and autophagosomes
What is the ubiquitin-proteasome pathway?
The major contributor to total cellular protein turnover
Ubiquitin is a small protein that can be covalently attached to proteins that have been targeted for degradation, proteasome is a huge macro-molecular complex in the cytosol that contains unfoldases and protease which degrades polyubiquitinated proteins into small peptides which are the degrades by peptidases to form amino acids- found in animals and plants
What is the first reason why it is necessary for macromolecules in cells to be turned over?
To control the time course of gene expression
Proteins and mRNAS encoding them may need to be turned on and off rapidly in the cell
mRNAs are degraded by ribonucleases- ubiquitous contaminant in chemicals and equipment- major source of experimental error in RNA experiments
What is the second reason why it is necessary for macromolecules in cells to be turned over?
Proteins may misfold
Chaperones catalyse the conversion of newly synthesised proteins into their native conformation
If protein goes wrong it is degraded by protease enzymes
Some misfolded proteins are stable and can form an insoluble aggregate and can cause disease
What is the third reason why it is necessary for macromolecules in cells to be turned over?
3)Cumulative damage to the molecules
Reactive oxygen species are produced as a bi-product of oxidative phosphorylation and these are highly corrosive species
Reactive oxygen species can be produced by UV light and can be useful to fight infection
Reactive oxygen species contain hydrogen peroxide and cause damage to biological molecules e.g. misfold proteins, damage DNA and oxidise lipids
Sometimes oxidised lipids (oxidised by the hydroxyl radical) are not degraded and replaced- instead they accumulate in walls of blood vessels- atherosclerosis
How are organelles turned over?
They undergo autophagy- self-eating
A donor organelle releases vesicles which fuse together to form a double membrane organelle which gradually wraps itself around a lump of the cytoplasm, including the organelles forming an autophagosome- it is unclear what organelles release these vesicles
This autophagosome fuses with a lysosome and the lysosome digests the contents of the autophagosome
The autophagosome in effect is an organelle bounded by a double membrane but it only forms when autophagy occurs
How can DNA be damaged in a cell?
DNA needs to be turned over because there are many ways it can be damaged in living cells
Deoxynucleotides can be damaged by ROS, breaking of bonds via hydrolysis and methylation of the DNA
What is a mechanism for DNA repair? outline this mechanism
Nucleotide excision repair
Involves damaged region being removed by DNA excision nuclease, and then DNA helicase unwinds the strand before DNA polymerase remakes the strand and DNA ligase reforms the Sugar Phosphate Backbone
The fragment that has been removed can be degraded- useful markers of ROS damage
