Oxidative Stress Flashcards
Define oxidative stress
- The imbalance between free radicals and antioxidants in the body
- too much free radicals or too little antioxidants
Give examples of diseases oxidative stress is linked to
- Cardiovascular
- COPD
- Alzheimer’s
- Cancer
- Multiple sclerosis
- Parkinson’s
What is a free radical?
An atom/molecule that contains one or more unpaired electron(s)
How is a superoxide generated?
Oxygen takes an electron to form a superoxide
How is a peroxynitrite formed?
Nitric oxide reacts with superoxide
How is hydrogen peroxide formed?
Superoxide reacts with 2H+ and an electron
How do ROS damage DNA?
- ROS reacts with bases = mispair and mutation
- ROS reacts with sugar = strand breaks
How do ROS damage proteins?
- damage to backbone leads to fragmentation then degradation
- damage to side chains lead to lots of effects e.g. inappropriate disulphides formation.
-change in structure can lead to degradation or loss of function
How do ROS damage lipids?
Lipid peroxidation
- free radicals takes H+ from fatty acids
- lipid radical causes a chain reaction
- hydrophobic environment disrupted
List exogenous sources of biological oxidants?
- Radiation
- Pollutants
- Drugs e.g. primaquine (anti-malarial)
- Toxins e.g. herbicide
How can the mitochondria be a source of biological oxidants?
- Electrons can accidentally escape the ETC chain
- reacts with dissolved oxygen forming a superoxide
What is nitric oxide synthase (NOS)?
Converts Arginine to Citrulline and nitric oxide radical
Describe respiratory burst
Rapid release of superoxide (from NADPH oxidase) and H2O2 for phagocytic cells to destroy pathogens
List the three cellular defences of the body against ROS
- SOD and Catalase
- Glutathione
- free radical scavengers
Describe how Superoxide dismutase and Catalase is used as antioxidants
- SOD converts superoxide to H2O2 and oxygen
- Catalase converts H2O2 to H2O and O2
Explain how glutathione is an antioxidant
- GSH donates an electron to ROS to stabilise
- 2 GSH (oxidised) forms GSSH through disulphides bond formation
- regenerated by glutathione reductase from pentose phosphate pathway (needs NADPH)
Explain how free radical scavengers act as antioxidants and give examples
- They donate hydrogen (with its electron) to free radicals in a non enzymatic reaction
- e.g. vitamin E, Vitamin C, Melatonin
What is Galactosaemia?
Inability to metabolised galactose due to deficiency in any of the 3 following enzymes:
- galactokinase
- uridyl transferase
- UDP-galactose epimerase
This forces galactose to galactitol
What enzyme converts galactose to galactitol?
Aldose reductase
List symptoms of galactosaemia
- Cataracts
- Renal failure
- Vomiting
- Hypoglycaemia
How does G6PDH deficiency lead to haemolysis?
- Can’t convert NAD+ to NADPH in pentose phosphate pathway
- Lower GSH regenerated
- lipid peroxidation and protein damage to RBCs
RBCs carry oxygen and can only get NADPH from pentose phosphate pathway thus leads to haemolysis
What are Heinz bodies?
Precipitated haemoglobin (aggregates/cross-linked)
How is paracetamol overdose toxic?
Excess paracetamol produces the toxic metabolite NAPQI which leads to:
- Lipid peroxidation
- Damage to proteins
- Damage to DNA
How is paracetamol overdose treated?
Acetylcysteine = replenishes glutathione levels
