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Toxicology > Oxidative Stress > Flashcards

Oxidative Stress Flashcards

1
Q

what do hydroxyl radicals cause

A

peroxidation of membrane proteins

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2
Q

what does the Fenton reaction protect against

A

oxidative stress

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3
Q

what does glutathione catalyse

A

conversion of hydrogen peroxide to water

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4
Q

is paraquat a persistent organic pollutant (POP)?

A

yes

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5
Q

what is hydrogen peroxide an example of

A

a free radical

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6
Q

what happens to paraquat

A

it is metabolised to an electrophilic metabolite

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7
Q

what is resistant to oxidative damage

A

DNA

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8
Q

what converts superoxide anion to water

A

superoxide dismutase

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9
Q

what is the bulk of oxygen used for

A

mitochondria to generate ATP

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10
Q

what are the enzymes that catalyse these oxidation reactions

A

oxidases

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11
Q

what is the toxicity of oxygen a result of

A

its conversion to reactive oxygen species

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12
Q

what are the key molecular targets of reactive oxygen species

A

DNA, proteins and lipids

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13
Q

what are free radicals

A

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

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14
Q

what other process can free radicals be generated by

A

homolytic fission

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15
Q

what occurs during homolytic fission

A

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

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16
Q

when do oxygen free radicals form

A

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

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17
Q

what process results in the production of hydroxyl radical

A

fenton reaction

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18
Q

what happens in the fenton reaction

A

H2O2 + electron/ electron donor such as Fe2+

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19
Q

what occurs in the Haber-Weiss reaction

A

H2O2 reacts with O2

20
Q

what is oxidative stress

A

balance disturbance

21
Q

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

A

Keap1-Nrf2-ARE pathway

22
Q

what does oxidation of Keap1 molecules result in

A

dissociation of Nrf2 form the complex

23
Q

what happens to Nrf2 once it has dissociated from Keap1

A

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

24
Q

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

A

anti-oxidant defence elements (ARE)

25
Q

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

A
  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
26
Q

what is paraquat

A

non-selective contact herbicide

27
Q

when was paraquat use introduced

A

1960s

28
Q

chemical structure of paraquat

A

bipyridinium compound with two quaternary nitrogen groups

29
Q

where is paraquat still widely used

A

in developing countries

30
Q

what is paraquats target organ

A

lungs

31
Q

what else apart from the lungs can paraquat damage

A

kidney and liver

32
Q

what do effects on the lungs result in

A

anoxia

33
Q

what cells does paraquat accumulate in in the lungs

A

epithelial cells

34
Q

what happens in the two stages of lung damage

A
  1. cells of alveolar epithelium undergo necrosis = actute inflammatory reaction
  2. tissue oedema and fibrosis
35
Q

what is the most likely explanation of accumulation of paraquat

A

the structure of bipyridyl nucleus similar to diamine and polyamine

36
Q

two examples of oxygen free radicals

A 
O2 = superoxide
OH. = hydroxyl
37
Q

three examples of non-radical ROS

A 
H2O2 = hydrogen peroxide
HOCI = hydrochlorous acid 
ONOO- = peroxynitrite
38
Q

what two substances are dangerous to cells

A

hydrogen peroxide

peroxynitrite

39
Q

what type of molecule is glutathione?

A

tri-peptide

40
Q

what does paraquat lead to

A

excessive generation of superoxide anions

41
Q

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

A

polyunsaturated fatty acids

42
Q

how can damage by peroxidation of cell membrane be avoided

A
  1. free radical scavengers - vitamin E and Beta-carotene

2. glutathione peroxides detoxification

43
Q

what part of the Keap1 protein is the redox centre

A

thiol groups

44
Q

what happens upon binding to a thiol group of Keap1

A

Conformational change = dissociation of Nrf2

45
Q

what does dissociation of Nrf2 result in

A

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

Toxicology (9 decks)

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