Extreme environment

Question 1

damaging, toxic environments

Answer 1

• Radiation (especially UV light)
• Free radicals and oxidative stress
• Toxins and poisons (from bacteria, food etc)

Question 2

toxic agents

Answer 2

• Cholera toxin

- Ricin

Question 3

highly reactive oxygen species are created when

Answer 3

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

Question 4

Reactive oxygen species

Answer 4

[Check figure on slide 34]

Question 5

Reactive oxygen species (ROS), in particular the _____ __________, can react with ________

The initial reaction generates __________, which in turn can react with a second macromolecule to __________

Answer 5

• hydroxyl radical
• all biological macromolecules including lipids, proteins, nucleic acids and carbohydrates.
• a second radical
• continue the chain reaction.

Question 6

ROS modify the ________- of proteins and can lead to ________ of proteins.

Answer 6

• both the structure and function

- cross-linking or fragmentation

Question 7

the typical effects of reactive oxygen species on nucleic acids.

Answer 7

Modification of individual nucleotide bases, single-strand breaks and cross-linking

Question 8

Cells have a range of _______that help protect it from toxic environment damage.

Answer 8

anti-oxidant defences

Question 9

Glutathione

Answer 9

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.

Question 10

Superoxide dismutases

Answer 10

enzymes that convert highly reactive superoxide free radicals (O2-) to less reactive hydrogen peroxide (H2O2).

Question 11

What happened after the less reactive hydrogen peroxide (H2O2) is converted by ________?

Answer 11

• Superoxide dismutases

- Catalase (located in peroxisomes) then converts hydrogen peroxide to water and oxygen.

Question 12

Drug transporters

Answer 12

• 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

Question 13

Examples of drug transporter

Answer 13

[Check Slide 37 ]

Question 14

Damaged DNA must be repaired or ___________ will be formed.

Answer 14

mutations (permanent alterations to the DNA)

Question 15

In the DNA damage response cells do the following:

Answer 15

• 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

Question 16

Example of DNA damage

Answer 16

• Single strand break
• Double strand break
• Bulky adducts
• Base mismatches, insertions and deletions
• Base alkylation

Question 17

Cause of DNA damage

Answer 17

• Cellular Metabolism
• UV Light Exposure
• Ionizing Radiation
• Chemical exposure
• Replication errors

Question 18

Response of DNA damage

Answer 18

• 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

Question 19

Appox Duration of the cell cycle

Answer 19

G1 phase = 10-12 hrs
S phase = 4-6 hrs
G2 phase = 3-4 hrs
M phase = 1 hr

Question 20

Cell cycle check points

Answer 20

• 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

Question 21

Cells must be able to cope with fluctuations in their external environment including changes in:

Answer 21

• temperature
• pH
• nutrients
• oxygen
• UV light
• pathogens & toxins
• signals such as hormones, neurotransmitters etc

Question 22

During the response to _______ stress the cells undergo rapid changes to their metabolism and protect themselves against damage.

Answer 22

sub-lethal

Question 23

stresses

Answer 23

Beyond a certain threshold of environmetal changes

Question 24

Example of cellular changes response to sub-lethal stress

Answer 24

• Changes in membrane composition
• Switch to anaerobic metabolism
• Increased antioxidants
• Increased drug transporters
• DNA repair
• Quiescence
• Autophagy

Question 25

cancer

Answer 25

Strict control over cells goes wrong and the organism can’t function correctly.

Question 26

In cancer, cells ignore______ and start _________. Eventually _________

Answer 26

• ignore signals from other cells
• proliferating without any control or restraint.
• Eventually they lose social connections and move away from their original tissue

Question 27

DNA is constantly being damaged and repair is ________

Cancer is therefore more or less _________ and just a matter of time in most _______ organisms.

Answer 27

• not perfect therefore mutations occur.
• inevitable
• multi-cellular

Question 28

A cell’s defences are designed to delay cancer as long as possible, through:

Answer 28

• Antioxidants
• DNA repair
• Apoptosis
• Extracellular Matrix

Question 29

Cells are :

Answer 29

• compartmentalised
• specialised
• dynamic
• robust
• Social

Question 30

Robustness

Answer 30

the ability of a cell to maintain performance and function in the face of internal and external perturbations.
(key property of living systems)