Oxidative Stress

Question 1

what do hydroxyl radicals cause

Answer 1

peroxidation of membrane proteins

Question 2

what does the Fenton reaction protect against

Answer 2

oxidative stress

Question 3

what does glutathione catalyse

Answer 3

conversion of hydrogen peroxide to water

Question 4

is paraquat a persistent organic pollutant (POP)?

Answer 4

yes

Question 5

what is hydrogen peroxide an example of

Answer 5

a free radical

Question 6

what happens to paraquat

Answer 6

it is metabolised to an electrophilic metabolite

Question 7

what is resistant to oxidative damage

Answer 7

DNA

Question 8

what converts superoxide anion to water

Answer 8

superoxide dismutase

Question 9

what is the bulk of oxygen used for

Answer 9

mitochondria to generate ATP

Question 10

what are the enzymes that catalyse these oxidation reactions

Answer 10

oxidases

Question 11

what is the toxicity of oxygen a result of

Answer 11

its conversion to reactive oxygen species

Question 12

what are the key molecular targets of reactive oxygen species

Answer 12

DNA, proteins and lipids

Question 13

what are free radicals

Answer 13

atoms or molecules that exist independently and contain one or more unpaired electrons

Question 14

what other process can free radicals be generated by

Answer 14

homolytic fission

Question 15

what occurs during homolytic fission

Answer 15

each atom takes on of the electrons from the pair that makes up the covalent bond

Question 16

when do oxygen free radicals form

Answer 16

when a single electron is added to the molecule result in the formation of a superoxide anion

Question 17

what process results in the production of hydroxyl radical

Answer 17

fenton reaction

Question 18

what happens in the fenton reaction

Answer 18

H2O2 + electron/ electron donor such as Fe2+

Question 19

what occurs in the Haber-Weiss reaction

Answer 19

H2O2 reacts with O2

Question 20

what is oxidative stress

Answer 20

balance disturbance

Question 21

what is the best mechanism to date to detect and counter oxidative stress (maintain oxidative homeostasis)

Answer 21

Keap1-Nrf2-ARE pathway

Question 22

what does oxidation of Keap1 molecules result in

Answer 22

dissociation of Nrf2 form the complex

Question 23

what happens to Nrf2 once it has dissociated from Keap1

Answer 23

it migrates to the cell nucleus where it activates transcription genes that encode proteins involve in defence against oxidative stress

Question 24

what are elements that are involved in defence against oxidative stress called

Answer 24

anti-oxidant defence elements (ARE)

Question 25

what are the three main types of protection in vivo against free radicals

Answer 25

1. enzymes that catalyse the removal of ROS 2. small molecular mass antioxidants that scavenge ROS 3. proteins that trap pro-oxidants such as Fe ions

Question 26

what is paraquat

Answer 26

non-selective contact herbicide

Question 27

when was paraquat use introduced

Answer 27

1960s

Question 28

chemical structure of paraquat

Answer 28

bipyridinium compound with two quaternary nitrogen groups

Question 29

where is paraquat still widely used

Answer 29

in developing countries

Question 30

what is paraquats target organ

Answer 30

lungs

Question 31

what else apart from the lungs can paraquat damage

Answer 31

kidney and liver

Question 32

what do effects on the lungs result in

Answer 32

anoxia

Question 33

what cells does paraquat accumulate in in the lungs

Answer 33

epithelial cells

Question 34

what happens in the two stages of lung damage

Answer 34

1. cells of alveolar epithelium undergo necrosis = actute inflammatory reaction 2. tissue oedema and fibrosis

Question 35

what is the most likely explanation of accumulation of paraquat

Answer 35

the structure of bipyridyl nucleus similar to diamine and polyamine

Question 36

two examples of oxygen free radicals

Answer 36

``` O2 = superoxide OH. = hydroxyl ```

Question 37

three examples of non-radical ROS

Answer 37

``` H2O2 = hydrogen peroxide HOCI = hydrochlorous acid ONOO- = peroxynitrite ```

Question 38

what two substances are dangerous to cells

Answer 38

hydrogen peroxide | peroxynitrite

Question 39

what type of molecule is glutathione?

Answer 39

tri-peptide

Question 40

what does paraquat lead to

Answer 40

excessive generation of superoxide anions

Question 41

what component of the cell membrane is very vulnerable to oxidation?

Answer 41

polyunsaturated fatty acids

Question 42

how can damage by peroxidation of cell membrane be avoided

Answer 42

1. free radical scavengers - vitamin E and Beta-carotene | 2. glutathione peroxides detoxification

Question 43

what part of the Keap1 protein is the redox centre

Answer 43

thiol groups

Question 44

what happens upon binding to a thiol group of Keap1

Answer 44

Conformational change = dissociation of Nrf2

Question 45

what does dissociation of Nrf2 result in

Answer 45

gene transcription of anti-oxidant response elements E.G glutathione peroxidases or superoxide dismutase = redox homeostasis