Oxidative Stress

Question 1

Define oxidative stress

Answer 1

• The imbalance between free radicals and antioxidants in the body
• too much free radicals or too little antioxidants

Question 2

Give examples of diseases oxidative stress is linked to

Answer 2

• Cardiovascular
• COPD
• Alzheimer’s
• Cancer
• Multiple sclerosis
• Parkinson’s

Question 3

What is a free radical?

Answer 3

An atom/molecule that contains one or more unpaired electron(s)

Question 4

How is a superoxide generated?

Answer 4

Oxygen takes an electron to form a superoxide

Question 5

How is a peroxynitrite formed?

Answer 5

Nitric oxide reacts with superoxide

Question 6

How is hydrogen peroxide formed?

Answer 6

Superoxide reacts with 2H+ and an electron

Question 7

How do ROS damage DNA?

Answer 7

• ROS reacts with bases = mispair and mutation

- ROS reacts with sugar = strand breaks

Question 8

How do ROS damage proteins?

Answer 8

• 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

Question 9

How do ROS damage lipids?

Answer 9

Lipid peroxidation

• free radicals takes H+ from fatty acids
• lipid radical causes a chain reaction
• hydrophobic environment disrupted

Question 10

List exogenous sources of biological oxidants?

Answer 10

• Radiation
• Pollutants
• Drugs e.g. primaquine (anti-malarial)
• Toxins e.g. herbicide

Question 11

How can the mitochondria be a source of biological oxidants?

Answer 11

• Electrons can accidentally escape the ETC chain

- reacts with dissolved oxygen forming a superoxide

Question 12

What is nitric oxide synthase (NOS)?

Answer 12

Converts Arginine to Citrulline and nitric oxide radical

Question 13

Describe respiratory burst

Answer 13

Rapid release of superoxide (from NADPH oxidase) and H2O2 for phagocytic cells to destroy pathogens

Question 14

List the three cellular defences of the body against ROS

Answer 14

• SOD and Catalase
• Glutathione
• free radical scavengers

Question 15

Describe how Superoxide dismutase and Catalase is used as antioxidants

Answer 15

• SOD converts superoxide to H2O2 and oxygen

- Catalase converts H2O2 to H2O and O2

Question 16

Explain how glutathione is an antioxidant

Answer 16

• 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)

Question 17

Explain how free radical scavengers act as antioxidants and give examples

Answer 17

• They donate hydrogen (with its electron) to free radicals in a non enzymatic reaction
• e.g. vitamin E, Vitamin C, Melatonin

Question 18

What is Galactosaemia?

Answer 18

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

Question 19

What enzyme converts galactose to galactitol?

Answer 19

Aldose reductase

Question 20

List symptoms of galactosaemia

Answer 20

• Cataracts
• Renal failure
• Vomiting
• Hypoglycaemia

Question 21

How does G6PDH deficiency lead to haemolysis?

Answer 21

• 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

Question 22

What are Heinz bodies?

Answer 22

Precipitated haemoglobin (aggregates/cross-linked)

Question 23

How is paracetamol overdose toxic?

Answer 23

Excess paracetamol produces the toxic metabolite NAPQI which leads to:

• Lipid peroxidation
• Damage to proteins
• Damage to DNA

Question 24

How is paracetamol overdose treated?

Answer 24

Acetylcysteine = replenishes glutathione levels