Reactive oxidative species Flashcards
Only 0.1-2% of electrons drop out of the ETC, so why is this a major issue?
-It has a high cummulative effect, 0.1-2% of each mitochondria results in alot of O2* produced
Why are superoxide radicals produced in miotchondria?
- Electrons drop out of the ETC resulting in a free electron
- Superoxide radicals generated if the free electron is picked up by O2
What are the cellular defences against superoxide radicals?
- Superoxide dismutase oxidises O2* to H2O2
- Catalase oxidises H2O2 to H2O+O2
What are hydroxyl radicals produced from and what causes there production?
- H2O2 or O2
- Ionising radiation, eg, UV, X-rays, g-rays
What are hydroxyl radicals particularly damaging to?
-Cell membranes and DNA
How is NO* produced in the body?
-From arginine
Why is NO* produced in the body if it is harmful?
-Important signalling molecule
How is peroxynitrite produced?
-NO+O2->ONOO
What is peroxynitrite associated with?
-Inflammation
What is cells primary defence against ROS?
-Glutathione
How does glutathione act as an antioxidant?
-Donates H+ from cysteine to reduce ROS
What catalyses the reduction of ROS by glutathione?
-Glutathione peroxidase
What is the oxidised form of glutathione?
-GSSG
What are examples of exogenous oxidising agents?
- Drugs-> primaquine-> anti-malarial
- Toxins->paraquate-> poisons cells, often fatal
What is the secondary cellular defence against ROS?
NADPH
Where is NADPH produced?
-By G6PD in the pentose phosphate pathway
How is NADPH the secondary defence to ROS?
-Reduces GSSG back to GSH, catalysed by GSH reductase, therefore freeing up the antioxidant
How is NADPH important in maintaining protein structure?
-DSB formation is in equilibrium, constantly being made and constantly reduced by NADPH in order to maintain proper protein structure and stop denaturation
Why is NADPH important in galactosaemia?
- Galactose accumulates in the eye and is oxidised to galactitol by aldose reductase
- This reaction uses NADPH, producing NADP+
- There is no NADPH to keep DSB from forming leading to cataracts
Why is NADPH significant in G6PD deficiency?
- No G6PD to reduce NADP+ to NADPH
- No NADPH to reduce GSSG
- Inappropriate DSB formation and ROS damage
- Can lead to the formation of heinz bodies and haemolysis
Name some exogenous antioxidants
- Vitamins C, E, A
- Flavenols - b-carotene
- Minerals- selenium and zinc
What are the steps of protection against H2O2?
- Glutathione reduces H2O2 to H2O and O2
- NADPH replenishes GSH
- NADPH replenished by PPP
When does oxidative stress occur?
- When there is an imbalance between ROS and protective mechanisms
i. e increased production or saturated defences
What is lipid peroxidation?
-Reaction of ROS with unsaturated lipids to form lipid peroxides
