B2.010 Oxidative Balance in Ischemic Damage and Blood Pressure Flashcards
what are the 4 primary ROS?
molecular O2
OH- anion
OH* radical
superoxide O2-*
what nitrogen species is reactive?
nitric oxide NO*
what species have unstable O-O bonds?
H2O2 hydrogen peroxide
ONOO- peroxynitrite
what is the pathways for the interconversion of ROS?
O2 + e- makes superoxide O2-*
2O2-* + 2H+ is catalyzed by SOD to make H2O2 and O2
H2O2 interacts with free metal in the Fenton rxn to produce HO* radical and OH- anion
how is NO* converted to HO* and NO2?
NO* + O2-* make ONOO-
ONOO- and H+ make HO* and NO2
what are 4 processes enabled by ROS?
energy production, signaling molecules, inflammation/immunity, cell redox balance
what proteins are related to ROS processes?
mitochondrial EC chain, nitric oxide synthase, AA metabolism, NADPH oxidase, cyt P450, xanthine oxidase
in oxidative stress, what do ROS chemically attack?
nucleic acid structures, amino acid side chains, double bonds of unsaturated fatty acids
what anti-oxidant enzymes are located within the mitochondria?
SOD2
Glutathione Peroxidase/Reductase
Peroxiredoxin (3 or 5)/ Thioredoxin Reductase 2
what anti-oxidant enzymes are located in the cytoplasm?
catalase
SOD1
Glutathione Peroxidase/Reductase
Peroxiredoxin/ Thioredoxin Reductase 1
what antioxidant makes up 1% of soluble protein?
superoxide dismutase (SOD)
what enzyme turns peroxide into water and oxygen?
catalase
what is the most important non-enzymatic antioxidant? (as noted by Dr. Swint-Kruse)
glutathione
what are hydrophilic non-enzymatic antioxidants?
glutathione, cysteine, vitamin C, urate, bilirubin, metal binding proteins
what are hydrophobic non-enzymatic antioxidants?
vitamin E, beta carotene
how do non-enzymatic antioxidants work?
accept or donate electrons becoming radicals themselves, new radicals are more stable than the neutralized radical due to resonance
what is the function of the e- transport chain?
create a proton gradient for ATP production by passing e- down chain
what percentage of e- leak from the chain and don’t make it through complex 4?q
1-4%
what is the fate of e- that don’t make it through the chain?
form superoxide with molecular oxygen
what chemicals completely block the e- transport chain and how?
CN and CO, by blocking complex 4 function
if a large number of substrates feed the citric acid cycle, what are the ROS and ATP outcomes?
ROS and ATP both increase
how could a transcription factor counter-act mitochrondrial stress caused by an influx in substrates feeding the citric acid cycle?
make more ADP to slow down citric acid cycle
what happens to the ROS balance in ischemia and reperfusion?
wild swings
what are the results of ischemia on mitochondrial function?
ATP synthase is blocked due to lack of oxygen, which blocks proton gradient and causes leakage of free e-
