Session 1 - oxidative stress and antioxidants Flashcards
How do free radicals cause damage?
They taken an electron from protein/lipid/DNA
for their unpaired one(s)
How does hydrogen peroxide (H2O2) produce free radicals?
Reacts with other molecules (like Fe2+) to produce free radicals
Superoxide radicals react with nitric oxide radicals to make what?
ONOO-
peroxynitrite
highly reactive and can oxidise more molecules
Which herbicide produces superoxide radicals?
paraquat
Which type of DNA is especially sensitive to ROS damage?
Why?
mitochondrial DNA (mtDNA)
- Near the inner mitochondrial membrane where ROS are formed
- not protected by histones
What are Heinz bodies?
Inclusions in Red blood cells made of denatured haemoglobin due to ROS damage
How do ROS cause inappropriate crosslinking?
Takes an electron from a cysteine residue (thiol group; S-H) converting it to a disulphide bond
S-H > S-S
How can ROS damage lead to atherosclerosis?
Lipid peroxidation of the membrane lipids disrupts the integrity and hydrophobicty of the membrane
(it damages the endothelium which leads to plaque formation)
Which enzymes can break superoxide radicals down?
- Superoxide dismutase
(converts to hydrogen peroxide and water) - Catalase
(converts H2O2 to water and oxygen)
How does Glutathione protect from ROS damage?
The reduced form of glutathione (GSH) is continuously recycled so that it can reduce hydrogen peroxide to water.
(Usually abundant so a first line defense against ROS)
What type of molecule is glutathione?
anti-oxidant
Which enzyme catalyses oxidation of glutathione?
What co-factor does it require?
How does this protect from ROS?
Glutathione peroxidase
selenium
glutathione donates an electron from a cysteine residue which reduces H2O2 to water.
How is the oxidised form of glutathione (GSSG) converted back to the protective form?
What is the reducing agent?
glutathione reductase reduces GSSG back to 2GSH
NADPH > NADP
Which form of glutathione is protective against ROS?
The reduced form; 2GSH
How does eating your 5 a day contribute to ROS protection?
Vitamin C
Vitamin E (nuts/seeds)
Carotenoids (carrots, oranges)
Melatonin (bananas)
are all antioxdiants/ free radical scavengers
Which are the lipid soluble vitamins?
What type of ROS damage can Vitamin E protect against?
ADEK
lipid peroxidation
lipid soluble
What is oxidative stress?
Too many free radicals
How can inflammation lead to ROS damage?
- INOS, inducible NO synthase activated in inflammation
- Produces nitric oxide radicals
- React with superoxide radicals to to form ONOO- (peroxynitrite)
Which enzyme facilitates the respiratory burst of neutrophils & monocytes?
NADPH oxidase
- oxidises NADPH and reduces oxygen to superoxide molecules which are released at the pathogen
Why is a sufficient store of NADPH important in ROS protection?
need it to recycle oxidised glutathione (GSSG) back to the protective reduced form (2GSH)
(glutathione is an antoxidant)
Patients with galactosaemia can’t meatbolise ____?
Which enzyme is overactive and how does this affect oxidative damage?
galactose
aldose reductase
consumes excess NADPH which is needed to maintain a store of reduced glutathione (GSH) to neutralise radicals
- less protectrion from ROS
In which pathway is NADPH produced?
Which enzyme is first in this pathway and what happens in a deficiency?
pentose phosphate pathway
Glucose 6 phosphate dehydrogenase
G6PDH deficiency limits the amount of NADPH produce which reduces protection form oxidative damage
How much paracetamol is a toxic dose?
Which drug should be given in an overdose?
Within what time period?
10g +
N-acetylcysteine
within 8 hours to prevent liver failure
How does a paracetamol overdose kill you?
- Paracetamol at a toxic dose (10g) saturates the usual pathways of metabolism
- Metabolised to NAPQI;
Extremely hepatotoxic
Oxidises glutathione (GSH) - Liver damage due to hepatotoxicity and increased susceptibility to oxidative stress
- Progress to liver failure and death
