Biochemistry-O2 Toxicity Flashcards
What are the ROS?
Superoxide, Hydrogen Peroxide, Hydroxyl Radical
Where is the majority of superoxide produced?
ETC’s Coenzyme Q in the mitochondria lets some electrons escape and get taken by oxygen to give rise to superoxide.
Where do you see production of hydrogen peroxide in the body?
Monamine Oxidase (MAO) which deactivates neurotransmitters and oxidizes fatty acids in peroxisomes.
What is the most damaging ROS? Least damaging?
Most = hydroxyl radical. Least = hydrogen peroxide.
Where do you see production of hydroxyl radical in the body?
Fenton reaction (needs a reduced metal like Fe2+. Superoxide & vitamin C can convert Fe3+ -> Fe2+ to cause the fenton reaction). UV radiation can also split water to form the hydroxyl radical.
What type of ROS is used in medical therapies to destroy certain cells?
Singlet oxygen (double bonded oxygen)
How can ROS affect the cell membrane?
Hydroxyl radical takes away H+ -> Lipid radical formation -> Lipid radical reacts w/O2 -> lipid peroxyl radical -> lipid hydroperoxide (more permeable bilayer) + ANOTHER LIPID RADICAL
What is the role of ROS in progression of atherosclerosis?
Minimally oxidized LDL gets into the intimal layer of the artery -> Macrophages release ROS onto LDL to attack it -> the now maximally oxidized LDL is taken up by macrophages -> foamy cells -> plaque w/necrotic core.
Hydroxyl radical attack on DNA causes what devastating change to the host DNA?
Guanine -> 8-Hydroxyguanine. 8-Hydroxyguanine preferentially binds adenine over cytosine which messes up the whole genome.
How can inflammation from atherosclerosis cause increase generation of RNOS?
Nitric oxide (NO) reacts with superoxide to from peroxynitrate. During inflammation, NO levels are high and more damaging peroxynitrate is produced.
How do neutrophils utilize ROS and RNOS?
HOCL (hypochlorous acid), OH (hydroxyl radical) and ONOO (peroxynitrate) are all produced to attack bacteria
How does superoxide dismutase work?
The oxidized state produces O2 from superoxide. The reduced state produces hydrogen peroxide from superoxide. Zn and Cu are needed cofactors for this reaction.
What disease is mutation of SOD1 (superoxide dismutase) gene associated with?
Amyotrophic Lateral Sclerosis.
How does catalase work?
It is mainly found in the peroxisomes. It reduces hydrogen peroxide to water and O2.
How does glutathione peroxidase work?
It reduces hydrogen peroxide to water. Note that it requires the cofactor Se.
What defense mechanism is employed by the cell to limit disruption of the bilayer by lipid hydroperoxide?
Glutathion peroxidase can reduce the lipid hydroperoxide to an alcohol.
How does vitamin E prevent free radical disruption of the bilayer?
It blocks free radical reaction by capturing the free radicals and preventing propagation of lipid peroxidation.
How does vitamin C limit free radical destruction? How can it cause free radical destruction?
L-ascorbate (reduced form of vitamin C) donates electrons to free radicals to detoxify them. Its effects can be reversed because it can also reduce Fe3+ to Fe2+ and initiate the fenton reaction.
What is vitamin A’s role thought to be in detoxifying ROS?
Mainly detoxification of singlet oxidation.
Why might people with gout have less free radical damage?
Uric acid can capture electrons and still be stable.
Why doesn’t chocolate get rancid.
Catechin is an antioxidant that prevents oxidative damage.
