Extreme environment Flashcards
damaging, toxic environments
- Radiation (especially UV light)
- Free radicals and oxidative stress
- Toxins and poisons (from bacteria, food etc)
toxic agents
- Cholera toxin
- Ricin
highly reactive oxygen species are created when
this last step of the ATP producing process through the electron transport chain doesn’t work properly : The oxygen electron acceptor didn’t accepts four electrons
Reactive oxygen species
[Check figure on slide 34]
Reactive oxygen species (ROS), in particular the _____ __________, can react with ________
The initial reaction generates __________, which in turn can react with a second macromolecule to __________
- hydroxyl radical
- all biological macromolecules including lipids, proteins, nucleic acids and carbohydrates.
- a second radical
- continue the chain reaction.
ROS modify the ________- of proteins and can lead to ________ of proteins.
- both the structure and function
- cross-linking or fragmentation
the typical effects of reactive oxygen species on nucleic acids.
Modification of individual nucleotide bases, single-strand breaks and cross-linking
Cells have a range of _______that help protect it from toxic environment damage.
anti-oxidant defences
Glutathione
The major anti-oxidant in cells. It is synthesised in high amounts in cells (up to 5 mM in the liver). In its reduced form it readily donates electrons to reactive oxygen species, forming more stable molecules.
Superoxide dismutases
enzymes that convert highly reactive superoxide free radicals (O2-) to less reactive hydrogen peroxide (H2O2).
What happened after the less reactive hydrogen peroxide (H2O2) is converted by ________?
- Superoxide dismutases
- Catalase (located in peroxisomes) then converts hydrogen peroxide to water and oxygen.
Drug transporters
- Transmembrane proteins that use ATP to transport substances across membranes.
- To prevent damage
- Found in high concentrations in the blood-brain barrier, hepatocytes in the liver and in stem cells.
- can transport a wide range of substances, including toxins and drugs
Examples of drug transporter
[Check Slide 37 ]
Damaged DNA must be repaired or ___________ will be formed.
mutations (permanent alterations to the DNA)
In the DNA damage response cells do the following:
- DNA damage is detected
> Cells stop going through the cell cycle
> DNA repair is initiated
> If the DNA damage is too extensive the cell undergoes apoptosis
Example of DNA damage
- Single strand break
- Double strand break
- Bulky adducts
- Base mismatches, insertions and deletions
- Base alkylation
Cause of DNA damage
- Cellular Metabolism
- UV Light Exposure
- Ionizing Radiation
- Chemical exposure
- Replication errors
Response of DNA damage
- Cell Cycle Checkpoint activation
- Transciptional Program activation
- DNA repair :
- Direct reversal
- Base excision repair
- Nucleotide excision repair
- Mismatch repair
- Double strand break repair
(~ Homologous recombination
~ Non- homologous end joining) - Apoptosis
Appox Duration of the cell cycle
G1 phase = 10-12 hrs
S phase = 4-6 hrs
G2 phase = 3-4 hrs
M phase = 1 hr
Cell cycle check points
- at the end of G1 phase, entrance into S phase is blocked if genome is demaged
- In the middle of S phase, DNA replication halted if genome is damaged
- At the end of G2 phase, entrance into M phase blocked if DNA replication is not completed
- During M phase, anaphase blocked if chromatids are not properly assembled on mitotic spindle
Cells must be able to cope with fluctuations in their external environment including changes in:
- temperature
- pH
- nutrients
- oxygen
- UV light
- pathogens & toxins
- signals such as hormones, neurotransmitters etc
During the response to _______ stress the cells undergo rapid changes to their metabolism and protect themselves against damage.
sub-lethal
stresses
Beyond a certain threshold of environmetal changes
Example of cellular changes response to sub-lethal stress
- Changes in membrane composition
- Switch to anaerobic metabolism
- Increased antioxidants
- Increased drug transporters
- DNA repair
- Quiescence
- Autophagy