Oxidative Stress Flashcards
what do hydroxyl radicals cause
peroxidation of membrane proteins
what does the Fenton reaction protect against
oxidative stress
what does glutathione catalyse
conversion of hydrogen peroxide to water
is paraquat a persistent organic pollutant (POP)?
yes
what is hydrogen peroxide an example of
a free radical
what happens to paraquat
it is metabolised to an electrophilic metabolite
what is resistant to oxidative damage
DNA
what converts superoxide anion to water
superoxide dismutase
what is the bulk of oxygen used for
mitochondria to generate ATP
what are the enzymes that catalyse these oxidation reactions
oxidases
what is the toxicity of oxygen a result of
its conversion to reactive oxygen species
what are the key molecular targets of reactive oxygen species
DNA, proteins and lipids
what are free radicals
atoms or molecules that exist independently and contain one or more unpaired electrons
what other process can free radicals be generated by
homolytic fission
what occurs during homolytic fission
each atom takes on of the electrons from the pair that makes up the covalent bond
when do oxygen free radicals form
when a single electron is added to the molecule result in the formation of a superoxide anion
what process results in the production of hydroxyl radical
fenton reaction
what happens in the fenton reaction
H2O2 + electron/ electron donor such as Fe2+
what occurs in the Haber-Weiss reaction
H2O2 reacts with O2
what is oxidative stress
balance disturbance
what is the best mechanism to date to detect and counter oxidative stress (maintain oxidative homeostasis)
Keap1-Nrf2-ARE pathway
what does oxidation of Keap1 molecules result in
dissociation of Nrf2 form the complex
what happens to Nrf2 once it has dissociated from Keap1
it migrates to the cell nucleus where it activates transcription genes that encode proteins involve in defence against oxidative stress
what are elements that are involved in defence against oxidative stress called
anti-oxidant defence elements (ARE)
what are the three main types of protection in vivo against free radicals
- enzymes that catalyse the removal of ROS
- small molecular mass antioxidants that scavenge ROS
- proteins that trap pro-oxidants such as Fe ions
what is paraquat
non-selective contact herbicide
when was paraquat use introduced
1960s
chemical structure of paraquat
bipyridinium compound with two quaternary nitrogen groups
where is paraquat still widely used
in developing countries
what is paraquats target organ
lungs
what else apart from the lungs can paraquat damage
kidney and liver
what do effects on the lungs result in
anoxia
what cells does paraquat accumulate in in the lungs
epithelial cells
what happens in the two stages of lung damage
- cells of alveolar epithelium undergo necrosis = actute inflammatory reaction
- tissue oedema and fibrosis
what is the most likely explanation of accumulation of paraquat
the structure of bipyridyl nucleus similar to diamine and polyamine
two examples of oxygen free radicals
O2 = superoxide OH. = hydroxyl
three examples of non-radical ROS
H2O2 = hydrogen peroxide HOCI = hydrochlorous acid ONOO- = peroxynitrite
what two substances are dangerous to cells
hydrogen peroxide
peroxynitrite
what type of molecule is glutathione?
tri-peptide
what does paraquat lead to
excessive generation of superoxide anions
what component of the cell membrane is very vulnerable to oxidation?
polyunsaturated fatty acids
how can damage by peroxidation of cell membrane be avoided
- free radical scavengers - vitamin E and Beta-carotene
2. glutathione peroxides detoxification
what part of the Keap1 protein is the redox centre
thiol groups
what happens upon binding to a thiol group of Keap1
Conformational change = dissociation of Nrf2
what does dissociation of Nrf2 result in
gene transcription of anti-oxidant response elements E.G glutathione peroxidases or superoxide dismutase = redox homeostasis
