Oxidative Stress Flashcards

1
Q

What diseases can be caused by oxidative stress

A

Cardiovascular disease, COPD, Cancer, Pancreatitis, MS

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2
Q

What are free radicals

A

An atom or molecule that contains one or more unpaired electrons
They are very reactive and take electrons from other atoms, molecules and ions

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3
Q

How does a superoxide form

A

Addition of an electron to oxygen

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4
Q

How is hydrogen peroxide formed

A

The addition of 2 hydrogen ions and an electron to a superoxide

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5
Q

How does a hydroxyl radical form

A

The addition of an electron and hydrogen to hydrogen peroxide

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6
Q

What are the 3 reactive oxygen species

A

Superoxide
Hydrogen peroxide
Hydroxyl radical

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7
Q

What are the 2 nitrogen reactive species

A

Nitric oxide

Peroxynitrate

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8
Q

How is peroxyntirite formed

A

Reaction of a superoxide and nitric oxide

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9
Q

which is the most damaging free radical

A

hydroxyl radical

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10
Q

how do reactive oxygen species damage DNA

A
  • react with the bases leading to mispairing and mutation

- react with the sugar causing strand breakages and mutation

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11
Q

the amount of what molecule can be used to measure oxidative damage

A

8-oxo-dG

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12
Q

how do reactive oxygen species damage proteins

A
  • by taking an electron from the backbone leading to fragmentation and degradation
  • or the sidechain changing the protein structure which can either cause degradation, loss or gain in function
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13
Q

how can disulphide bridges form due to ROS

A

if ROS take electrons from cysteine residues

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14
Q

why can disulphide bonds disrupt function of a protein

A

as they cause misfolding and crosslinking

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15
Q

how to ROS damage lipids

A
  • extract a hydrogen atom from a polyunsaturated fatty acid on the membrane
  • the lipid radical then reacts with oxygen to form lipid peroxyl radical
  • these cause lipid peroxidation
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16
Q

what is lipid peroxidation

A

a chain reaction of lipid peroxyl radicals stealing electrons off nearby fatty acids

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17
Q

why does is the damage to lipids de to ROS dangerous

A

the lipid bilayer is disrupted and so membrane integrity fails

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18
Q

give examples of exogenous sources of oxidants

A

radiation
pollutants
drugs
toxins

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19
Q

true or false: anti malarial drugs are a source of exogenous oxidants

A

true

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20
Q

give examples of endogenous oxidants

A

electron transport chain
nitric oxide synthases
NADPH oxidases

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21
Q

how does the electron transport chain cause the production of oxidants

A

an electron may escape from the chain and react with dissolved oxygen to form a superoxide

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22
Q

what are the 3 types of nitric oxide synthase

A

iNOS - inducible nitric oxide synthase
eNOS - endothelial nitric oxide synthase
nNOS - neuronal nitric oxide synthase

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23
Q

what does nitric oxide synthase do

A

produces nitric oxide from arginine

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24
Q

does nitric oxide synthase require NADPH?

A

yes and oxygen

25
Q

what does nitric oxide do

A

it is a signalling molecule which causes vasodilation, neurotransmission and is used in phagocytosis

26
Q

what is respiratory burst

A

rapid release of superoxide and hydrogen peroxide from phagocytes and peroxynitritie to destroy bacteria

27
Q

outline respiratory burst

A
  • phagocyte produces superoxide from oxygen taking and electron from NADPH using NADPH oxidase
  • iNOS produces nitric oxide
  • nitric oxide combines with the superoxide to form peroxynitrite
  • superoxide also form hydrogen peroxide
  • hydrogen peroxide is converted into hypochlorite by myeloperoxidase
  • hypochlorite and peroxynitrate are used to kill bacteria
28
Q

what do genetic defects in NADPH oxidase cause

A

increased susceptibility to bacterial infections

29
Q

what does NADPH oxidase do

A

causes the production of superoxide from oxygen by adding an electron from NADPH

30
Q

what 2 enzymes defend against ROS

A

superoxide dismutase and catalase

31
Q

what does superoxide dismutase do

A

converts superoxide into hydrogen peroxide and oxygen

32
Q

what does catalase do

A

converts hydrogen peroxide into water and oxygen

33
Q

what does glutathione do

A

protects against oxidative damage as the cysteine residue donates an electron to the ROS and then reacts with another glutathione to form a disulphide

34
Q

what enzyme catalyses the disulphide bond formation in glutathione molecules

A

glutathione peroxidase

35
Q

what element does glutathione require

A

selenium

36
Q

how is the disulphide glutathione converted back

A

by the enzyme glutathione reductase which uses enzymes from NADPH

37
Q

where is the source of NADPH from for the production of glutathione

A

pentose phosphate pathway

38
Q

why are red blood cells more susceptible to oxidative stress

A

as the pentose phosphate pathway is the only NADPH production for these cells and so they cant produce lots of NADPH to reform glutathione

39
Q

what 2 vitamins are used to defend against ROS

A

vitamin E

vitamin C

40
Q

what does vitamin E do

A

lipid soluble

protects against lipid peroxidation

41
Q

what does vitamin C do

A

water soluble

regenerate reduced form of vitamin E

42
Q

what do free radical scavengers do

A

reduce free radical damage by donating hydrogen atoms and its electron to free radicals in nonenzymatic reactions

43
Q

give examples of free radical scavengers

A

vitamins E and C
uric acid
melanin

44
Q

what is oxidative stress

A

when there are more oxidants than antioxidants in the body

45
Q

what causes galactosaemia

A

deficiency of any of the following:

  • UDP galactose epimerase
  • uridyl transferase
  • galactokinase
46
Q

how do ROS contribute to galactosaemia

A

deficiency of an enzyme in galactose metabolism causes the accumulation of galactose. Aldose Reductase uses NADPH to convert galactose into Galactitol. this builds up to form cataracts

47
Q

what are symptoms of galactosaemia

A

cataracts, vomiting, renal failure, liver failure, brain damage

48
Q

why is a deficiency in uridyl transferase worse than for galactokinase

A

without uridyl transferase there is a build up of galactose 1P which accumulates in the brain, liver, kidneys preventing ATP production causing damage

49
Q

what is haemolysis

A

when protein damage causes aggregations of linked haemoglobin called Heinz bodies

50
Q

what are Heinz bodies a clinical signal of

A

G6PDH deficiency

51
Q

what do Heinz bodies do

A

bind to cell membranes of RBC making it harder to squeeze them through capillaries

52
Q

what organ removes Heinz bodies

A

spleen

53
Q

why does a G6PDH deficiency provide less protection from oxidative stress

A

less NADPH is produced so less glutathione is reformed so theres less protection

54
Q

what dangerous molecule builds up in a paracetamol overdose

A

NAPQI

55
Q

how does the body safely metabolise NAPQI

A

by conjugation with glutathione

56
Q

why does the bodies store of glutathione decrease

A

due to oxidative stress

57
Q

what antidote is used in paracetamol overdose

A

acetylcysteine which replenishes the bodies glutathione levels

58
Q

at a prescribed dosage how is paracetamol normally metabolised

A

in conjugation with sulphate or glucuronide