Oxygen Toxicity Flashcards

1
Q

O2 is essential for life but is also

A

very toxic

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2
Q

If O2 accepts electron it beomces

A

highly reactive radical

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3
Q

highly reactive radical oxygen can do what

A

damage lipid, protein, or DNA

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4
Q

what do cells use to protect against ROS

A

antioxidants

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5
Q

what does ROS stand for

A

reactive oxygen species

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6
Q

O2- is called

A

superoxide

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7
Q

glucose produces intermediates of glycolysis, some of them will do what

A

react and interact and produce methylglyoxal

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8
Q

what is methylglyoxal

A

powerful, reacts with amino groups

it will attach itself to proteins (DNA, carbodhydrates, etc) and modify them. this is part of aging process

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9
Q

glucose biproducts age cell?

A

yes - methylglyoxal attaches to protein, DNA, etc and changes it

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10
Q

name some defense enzymes to limit the amount of methylglyoxal harming cell

A

catalase
glutathione peroxidase
vitamin E, vitamin C
antioxidants

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11
Q

what are the major O2 metabolites produced by one electron reduction

A

superoxide, hydrogen peroxide, and the hydroxyl radical

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12
Q

why is hydorgen peroxide so toxic

A

it’s the raw material to produce hydroxide ion and hydroxyl radical in presence of iron

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13
Q

draw the fenton reaction (hydrogen peroxide with iron)

A

pg 5 (he likes this one!)

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14
Q

superoxide + H2O2 will produce

A

Oxygen + water + hydroxyl radical

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15
Q

dicarbonyls are very

A

toxic

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16
Q

show how diabetes induces premature aging

A

pg 6

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17
Q

what are the sources of ROS

A

accidental byproducts of normal enzymatic reactions
hydorggen peroxide product of oxidases in peroxisomes
toxic free radicals are required for inflammatory response (macrophages)
drugs, radiation, pollutants increase free radical formation

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18
Q

3-5% oxygen consumed is converted to

A

ROS

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19
Q

macrophages kill bacteria

A

by being very toxic to other things, but also introduce toxic stress on our body

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20
Q

where are ROS produced in body? at least the most of them

A

ETC

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21
Q

CoQ in ETC is major source of

A

O2- production

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22
Q

CoQ function

A

communicates complex II to III and IX

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23
Q

how does CoQ introduce O2-

A

One-electron reduced form of CoQ (CoQH.) is free witohout membrane and may accidentally transfer e- to O2 yielding O2-

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24
Q

major component of ROS

A

lipid bilayer

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25
Q

NO stands for

A

nitric oxide

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26
Q

arginine reaction

A

pg 14

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27
Q

mutations that disable NADPH oxidase get what disease

A

Chronic Granulamatous Disease (CGD)

28
Q

look at slide 19

A

19

29
Q

what are a major source of free radicals leaked from reactions

A

cytochrome P 450 enzymes

30
Q

NO is

A

nitric oxide

31
Q

NO is an example of

A

free radical

32
Q

NO is a biological messenger involved in

A

vasodilation, immune response, neurotransmission

33
Q

Nitroglycerin breaks down to

A

NO

34
Q

NO toxicity is usually not a problem, why?

A

there are very low amounts of it

35
Q

what are the three NOS genes

A

nNOS
eNOS
iNOS

36
Q

what is function of nNOS and eNOS

A

they are NO genes

they produce small amounts of NO for neurotransmission and vasodilation

37
Q

what regulates nNOS and eNOS

A

calcium

38
Q

what is function of iNOS

A

produces high and toxic levels of NO against microorganisms

39
Q

describe how free radical production is part of host defense

A

destroys tumor cells and microorganisms

40
Q

what is the respiratory burst

A

immune response. rapid consumption of O2 to produce a lot of radicals to fight off

41
Q

where is NADPH oxidase found

A

phagolysosome

42
Q

what does NADPH oxidase do, list the steps

A

generates O2- → H2O2

43
Q

describe structure of NADPH oxidase

A

Composed of 6 subunits including 2 cytochromes, CYPA & CYPB

44
Q

What does CGD stand for

A

Chronic Granulamatous Disease

45
Q

Describe Chronic Granulamatous Disease

A

NADPH oxidase doesn’t work

immunodeficiency since phagocytes can’t kill microorganism if they don’t produce O2-

46
Q

superoxide dismutase mutation is found in what disease

A

ALS, Lou Gehrig’s disease

47
Q

what is function of Myeloperoxidase

A

generates HOCl from H2O2

48
Q

HOCl destroys

A

bacteria very quickly!

49
Q

deficiency of Myeloperoxidase can result in

A

chronic fungal infections

50
Q

draw out the formation from NO radical

A

pg 20

51
Q

ONOO- is very

A

stable

52
Q

what can ONOO- do

A

can diffuse to interact with Met residues, -SH groups, aromatic rings (e.g. -> nitroguanosine)

53
Q

N2O3 what does it do?

A

interferes with lipid & protein function

54
Q

NO2* what does it do

A

initiates lipid peroxidation

55
Q

which is rose RNOS or ROS

A

RNOS

56
Q

how does acetaldehyde decrease protection from H2O2 and lipid peroxidation

A

it binds to glutathione

57
Q

What are AGEs

A

Advanced glycooxidation products

58
Q

describe lipfuscin

A

hallmark of aging
dark/liver spots
mixture of lipids & protein, involves glycation and AGEs

59
Q

Vit E protects against

A

is lipid-soluble antioxidant that protects against lipid peroxides in membranes.

60
Q

is vitamin E lipid soluble

A

yes

61
Q

what is function of vitamin C

A

primarily restores reduced form of Vit. E but may act directly on ROS & RNOS.

62
Q

how is uric acid antioxidant

A

direct scavenger esp. in upper airway

63
Q

how is flavonoids antioxidant

A

some inhibit xanthine oxidase, others chelate Fe & Cu

64
Q

how is melatonin antioxidant

A

scavanges ROS & RNOS

65
Q

name 6 nonenzymatic antioxidants

A
vitamin E & C
carotenoids
flavonoids
uric acid
melatonin