Essay Question: Many diseases have been linked to oxygen-derived free radicals. Using examples from a single disease of your choice, discuss how reactive oxygen species induce cellular damage that contributes to the pathophysiology of your chosen condition.
Introduction: (up to 10 Marks).
Students should be able to define what they understand by the terms free radical and oxidative stress.
- Oxidative stress occurs when excess ROS production overwhelms the cells anti-oxidant capacity.
- Free radical is an electrically uncharged atom or group of atoms that has an unpaired electron.
- Unpaired electrons cause molecular instability and results in the molecule acquiring stabilization either by donating or accepting an electron from another molecule.
- An attacked molecule, losing an electron, also becomes a free radical which can result in injurious chemical bond formation within proteins, lipids, and carbohydrates; the basis of cellular damage.
Main body of text: (up to 70 marks) – Content to include
Students should discuss
- Lipid peroxidation, the establishment of a chain of lipid peroxidation and peroxidation end point markers e.g. Malondialdehyde.
- Protein oxidation, OH. attack on proteins generates free radicals that react with O2 to produce alkoxyl and peroxyl radicals
- Oxidation of DNA, results in including base modifications, base-free (apurinic and apyrimidinic) sites, strand breakage, and DNA-protein cross-links. The most prevalent product of DNA oxidation is 8-hydroxy-2-deoxyguanosine (8-OHdG).
As a consequence of the above may be
Altered cell signalling - Impaired function of receptors, antibodies, signal transduction, transport proteins and enzymes.
Damaged Membranes – Mitochondrial (impaired ATP production, release of cytocrome C and initiation of apoptosis); Lysosome (release of hydrolytic enzymes and autodigestion);