Oxidative Stress Flashcards
What diseases can be caused by oxidative stress
Cardiovascular disease, COPD, Cancer, Pancreatitis, MS
What are free radicals
An atom or molecule that contains one or more unpaired electrons
They are very reactive and take electrons from other atoms, molecules and ions
How does a superoxide form
Addition of an electron to oxygen
How is hydrogen peroxide formed
The addition of 2 hydrogen ions and an electron to a superoxide
How does a hydroxyl radical form
The addition of an electron and hydrogen to hydrogen peroxide
What are the 3 reactive oxygen species
Superoxide
Hydrogen peroxide
Hydroxyl radical
What are the 2 nitrogen reactive species
Nitric oxide
Peroxynitrate
How is peroxyntirite formed
Reaction of a superoxide and nitric oxide
which is the most damaging free radical
hydroxyl radical
how do reactive oxygen species damage DNA
- react with the bases leading to mispairing and mutation
- react with the sugar causing strand breakages and mutation
the amount of what molecule can be used to measure oxidative damage
8-oxo-dG
how do reactive oxygen species damage proteins
- by taking an electron from the backbone leading to fragmentation and degradation
- or the sidechain changing the protein structure which can either cause degradation, loss or gain in function
how can disulphide bridges form due to ROS
if ROS take electrons from cysteine residues
why can disulphide bonds disrupt function of a protein
as they cause misfolding and crosslinking
how to ROS damage lipids
- extract a hydrogen atom from a polyunsaturated fatty acid on the membrane
- the lipid radical then reacts with oxygen to form lipid peroxyl radical
- these cause lipid peroxidation
what is lipid peroxidation
a chain reaction of lipid peroxyl radicals stealing electrons off nearby fatty acids
why does is the damage to lipids de to ROS dangerous
the lipid bilayer is disrupted and so membrane integrity fails
give examples of exogenous sources of oxidants
radiation
pollutants
drugs
toxins
true or false: anti malarial drugs are a source of exogenous oxidants
true
give examples of endogenous oxidants
electron transport chain
nitric oxide synthases
NADPH oxidases
how does the electron transport chain cause the production of oxidants
an electron may escape from the chain and react with dissolved oxygen to form a superoxide
what are the 3 types of nitric oxide synthase
iNOS - inducible nitric oxide synthase
eNOS - endothelial nitric oxide synthase
nNOS - neuronal nitric oxide synthase
what does nitric oxide synthase do
produces nitric oxide from arginine
does nitric oxide synthase require NADPH?
yes and oxygen
what does nitric oxide do
it is a signalling molecule which causes vasodilation, neurotransmission and is used in phagocytosis
what is respiratory burst
rapid release of superoxide and hydrogen peroxide from phagocytes and peroxynitritie to destroy bacteria
outline respiratory burst
- phagocyte produces superoxide from oxygen taking and electron from NADPH using NADPH oxidase
- iNOS produces nitric oxide
- nitric oxide combines with the superoxide to form peroxynitrite
- superoxide also form hydrogen peroxide
- hydrogen peroxide is converted into hypochlorite by myeloperoxidase
- hypochlorite and peroxynitrate are used to kill bacteria
what do genetic defects in NADPH oxidase cause
increased susceptibility to bacterial infections
what does NADPH oxidase do
causes the production of superoxide from oxygen by adding an electron from NADPH
what 2 enzymes defend against ROS
superoxide dismutase and catalase
what does superoxide dismutase do
converts superoxide into hydrogen peroxide and oxygen
what does catalase do
converts hydrogen peroxide into water and oxygen
what does glutathione do
protects against oxidative damage as the cysteine residue donates an electron to the ROS and then reacts with another glutathione to form a disulphide
what enzyme catalyses the disulphide bond formation in glutathione molecules
glutathione peroxidase
what element does glutathione require
selenium
how is the disulphide glutathione converted back
by the enzyme glutathione reductase which uses enzymes from NADPH
where is the source of NADPH from for the production of glutathione
pentose phosphate pathway
why are red blood cells more susceptible to oxidative stress
as the pentose phosphate pathway is the only NADPH production for these cells and so they cant produce lots of NADPH to reform glutathione
what 2 vitamins are used to defend against ROS
vitamin E
vitamin C
what does vitamin E do
lipid soluble
protects against lipid peroxidation
what does vitamin C do
water soluble
regenerate reduced form of vitamin E
what do free radical scavengers do
reduce free radical damage by donating hydrogen atoms and its electron to free radicals in nonenzymatic reactions
give examples of free radical scavengers
vitamins E and C
uric acid
melanin
what is oxidative stress
when there are more oxidants than antioxidants in the body
what causes galactosaemia
deficiency of any of the following:
- UDP galactose epimerase
- uridyl transferase
- galactokinase
how do ROS contribute to galactosaemia
deficiency of an enzyme in galactose metabolism causes the accumulation of galactose. Aldose Reductase uses NADPH to convert galactose into Galactitol. this builds up to form cataracts
what are symptoms of galactosaemia
cataracts, vomiting, renal failure, liver failure, brain damage
why is a deficiency in uridyl transferase worse than for galactokinase
without uridyl transferase there is a build up of galactose 1P which accumulates in the brain, liver, kidneys preventing ATP production causing damage
what is haemolysis
when protein damage causes aggregations of linked haemoglobin called Heinz bodies
what are Heinz bodies a clinical signal of
G6PDH deficiency
what do Heinz bodies do
bind to cell membranes of RBC making it harder to squeeze them through capillaries
what organ removes Heinz bodies
spleen
why does a G6PDH deficiency provide less protection from oxidative stress
less NADPH is produced so less glutathione is reformed so theres less protection
what dangerous molecule builds up in a paracetamol overdose
NAPQI
how does the body safely metabolise NAPQI
by conjugation with glutathione
why does the bodies store of glutathione decrease
due to oxidative stress
what antidote is used in paracetamol overdose
acetylcysteine which replenishes the bodies glutathione levels
at a prescribed dosage how is paracetamol normally metabolised
in conjugation with sulphate or glucuronide
