Oxygen Toxicity Flashcards
O2 is essential for life but is also
very toxic
If O2 accepts electron it beomces
highly reactive radical
highly reactive radical oxygen can do what
damage lipid, protein, or DNA
what do cells use to protect against ROS
antioxidants
what does ROS stand for
reactive oxygen species
O2- is called
superoxide
glucose produces intermediates of glycolysis, some of them will do what
react and interact and produce methylglyoxal
what is methylglyoxal
powerful, reacts with amino groups
it will attach itself to proteins (DNA, carbodhydrates, etc) and modify them. this is part of aging process
glucose biproducts age cell?
yes - methylglyoxal attaches to protein, DNA, etc and changes it
name some defense enzymes to limit the amount of methylglyoxal harming cell
catalase
glutathione peroxidase
vitamin E, vitamin C
antioxidants
what are the major O2 metabolites produced by one electron reduction
superoxide, hydrogen peroxide, and the hydroxyl radical
why is hydorgen peroxide so toxic
it’s the raw material to produce hydroxide ion and hydroxyl radical in presence of iron
draw the fenton reaction (hydrogen peroxide with iron)
pg 5 (he likes this one!)
superoxide + H2O2 will produce
Oxygen + water + hydroxyl radical
dicarbonyls are very
toxic
show how diabetes induces premature aging
pg 6
what are the sources of ROS
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
3-5% oxygen consumed is converted to
ROS
macrophages kill bacteria
by being very toxic to other things, but also introduce toxic stress on our body
where are ROS produced in body? at least the most of them
ETC
CoQ in ETC is major source of
O2- production
CoQ function
communicates complex II to III and IX
how does CoQ introduce O2-
One-electron reduced form of CoQ (CoQH.) is free witohout membrane and may accidentally transfer e- to O2 yielding O2-
major component of ROS
lipid bilayer
NO stands for
nitric oxide
arginine reaction
pg 14
mutations that disable NADPH oxidase get what disease
Chronic Granulamatous Disease (CGD)
look at slide 19
19
what are a major source of free radicals leaked from reactions
cytochrome P 450 enzymes
NO is
nitric oxide
NO is an example of
free radical
NO is a biological messenger involved in
vasodilation, immune response, neurotransmission
Nitroglycerin breaks down to
NO
NO toxicity is usually not a problem, why?
there are very low amounts of it
what are the three NOS genes
nNOS
eNOS
iNOS
what is function of nNOS and eNOS
they are NO genes
they produce small amounts of NO for neurotransmission and vasodilation
what regulates nNOS and eNOS
calcium
what is function of iNOS
produces high and toxic levels of NO against microorganisms
describe how free radical production is part of host defense
destroys tumor cells and microorganisms
what is the respiratory burst
immune response. rapid consumption of O2 to produce a lot of radicals to fight off
where is NADPH oxidase found
phagolysosome
what does NADPH oxidase do, list the steps
generates O2- → H2O2
describe structure of NADPH oxidase
Composed of 6 subunits including 2 cytochromes, CYPA & CYPB
What does CGD stand for
Chronic Granulamatous Disease
Describe Chronic Granulamatous Disease
NADPH oxidase doesn’t work
immunodeficiency since phagocytes can’t kill microorganism if they don’t produce O2-
superoxide dismutase mutation is found in what disease
ALS, Lou Gehrig’s disease
what is function of Myeloperoxidase
generates HOCl from H2O2
HOCl destroys
bacteria very quickly!
deficiency of Myeloperoxidase can result in
chronic fungal infections
draw out the formation from NO radical
pg 20
ONOO- is very
stable
what can ONOO- do
can diffuse to interact with Met residues, -SH groups, aromatic rings (e.g. -> nitroguanosine)
N2O3 what does it do?
interferes with lipid & protein function
NO2* what does it do
initiates lipid peroxidation
which is rose RNOS or ROS
RNOS
how does acetaldehyde decrease protection from H2O2 and lipid peroxidation
it binds to glutathione
What are AGEs
Advanced glycooxidation products
describe lipfuscin
hallmark of aging
dark/liver spots
mixture of lipids & protein, involves glycation and AGEs
Vit E protects against
is lipid-soluble antioxidant that protects against lipid peroxides in membranes.
is vitamin E lipid soluble
yes
what is function of vitamin C
primarily restores reduced form of Vit. E but may act directly on ROS & RNOS.
how is uric acid antioxidant
direct scavenger esp. in upper airway
how is flavonoids antioxidant
some inhibit xanthine oxidase, others chelate Fe & Cu
how is melatonin antioxidant
scavanges ROS & RNOS
name 6 nonenzymatic antioxidants
vitamin E & C carotenoids flavonoids uric acid melatonin
