Oxygen Toxicity

Question 1

O2 is essential for life but is also

Answer 1

very toxic

Question 2

If O2 accepts electron it beomces

Answer 2

highly reactive radical

Question 3

highly reactive radical oxygen can do what

Answer 3

damage lipid, protein, or DNA

Question 4

what do cells use to protect against ROS

Answer 4

antioxidants

Question 5

what does ROS stand for

Answer 5

reactive oxygen species

Question 6

O2- is called

Answer 6

superoxide

Question 7

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

Answer 7

react and interact and produce methylglyoxal

Question 8

what is methylglyoxal

Answer 8

powerful, reacts with amino groups

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

Question 9

glucose biproducts age cell?

Answer 9

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

Question 10

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

Answer 10

catalase
glutathione peroxidase
vitamin E, vitamin C
antioxidants

Question 11

what are the major O2 metabolites produced by one electron reduction

Answer 11

superoxide, hydrogen peroxide, and the hydroxyl radical

Question 12

why is hydorgen peroxide so toxic

Answer 12

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

Question 13

draw the fenton reaction (hydrogen peroxide with iron)

Answer 13

pg 5 (he likes this one!)

Question 14

superoxide + H2O2 will produce

Answer 14

Oxygen + water + hydroxyl radical

Question 15

dicarbonyls are very

Answer 15

toxic

Question 16

show how diabetes induces premature aging

Answer 16

pg 6

Question 17

what are the sources of ROS

Answer 17

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

Question 18

3-5% oxygen consumed is converted to

Answer 18

ROS

Question 19

macrophages kill bacteria

Answer 19

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

Question 20

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

Answer 20

ETC

Question 21

CoQ in ETC is major source of

Answer 21

O2- production

Question 22

CoQ function

Answer 22

communicates complex II to III and IX

Question 23

how does CoQ introduce O2-

Answer 23

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

Question 24

major component of ROS

Answer 24

lipid bilayer

Question 25

NO stands for

Answer 25

nitric oxide

Question 26

arginine reaction

Answer 26

pg 14

Question 27

mutations that disable NADPH oxidase get what disease

Answer 27

Chronic Granulamatous Disease (CGD)

Question 28

look at slide 19

Answer 28

19

Question 29

what are a major source of free radicals leaked from reactions

Answer 29

cytochrome P 450 enzymes

Question 30

NO is

Answer 30

nitric oxide

Question 31

NO is an example of

Answer 31

free radical

Question 32

NO is a biological messenger involved in

Answer 32

vasodilation, immune response, neurotransmission

Question 33

Nitroglycerin breaks down to

Answer 33

NO

Question 34

NO toxicity is usually not a problem, why?

Answer 34

there are very low amounts of it

Question 35

what are the three NOS genes

Answer 35

nNOS eNOS iNOS

Question 36

what is function of nNOS and eNOS

Answer 36

they are NO genes | they produce small amounts of NO for neurotransmission and vasodilation

Question 37

what regulates nNOS and eNOS

Answer 37

calcium

Question 38

what is function of iNOS

Answer 38

produces high and toxic levels of NO against microorganisms

Question 39

describe how free radical production is part of host defense

Answer 39

destroys tumor cells and microorganisms

Question 40

what is the respiratory burst

Answer 40

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

Question 41

where is NADPH oxidase found

Answer 41

phagolysosome

Question 42

what does NADPH oxidase do, list the steps

Answer 42

generates O2- → H2O2

Question 43

describe structure of NADPH oxidase

Answer 43

Composed of 6 subunits including 2 cytochromes, CYPA & CYPB

Question 44

What does CGD stand for

Answer 44

Chronic Granulamatous Disease

Question 45

Describe Chronic Granulamatous Disease

Answer 45

NADPH oxidase doesn't work | immunodeficiency since phagocytes can’t kill microorganism if they don’t produce O2-

Question 46

superoxide dismutase mutation is found in what disease

Answer 46

ALS, Lou Gehrig's disease

Question 47

what is function of Myeloperoxidase

Answer 47

generates HOCl from H2O2

Question 48

HOCl destroys

Answer 48

bacteria very quickly!

Question 49

deficiency of Myeloperoxidase can result in

Answer 49

chronic fungal infections

Question 50

draw out the formation from NO radical

Answer 50

pg 20

Question 51

ONOO- is very

Answer 51

stable

Question 52

what can ONOO- do

Answer 52

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

Question 53

N2O3 what does it do?

Answer 53

interferes with lipid & protein function

Question 54

NO2* what does it do

Answer 54

initiates lipid peroxidation

Question 55

which is rose RNOS or ROS

Answer 55

RNOS

Question 56

how does acetaldehyde decrease protection from H2O2 and lipid peroxidation

Answer 56

it binds to glutathione

Question 57

What are AGEs

Answer 57

Advanced glycooxidation products

Question 58

describe lipfuscin

Answer 58

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

Question 59

Vit E protects against

Answer 59

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

Question 60

is vitamin E lipid soluble

Answer 60

yes

Question 61

what is function of vitamin C

Answer 61

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

Question 62

how is uric acid antioxidant

Answer 62

direct scavenger esp. in upper airway

Question 63

how is flavonoids antioxidant

Answer 63

some inhibit xanthine oxidase, others chelate Fe & Cu

Question 64

how is melatonin antioxidant

Answer 64

scavanges ROS & RNOS

Question 65

name 6 nonenzymatic antioxidants

Answer 65

``` vitamin E & C carotenoids flavonoids uric acid melatonin ```