Oxidative Stress

Question 1

What is the problem with free radicals gaining electrons from other molecules?

Answer 1

This tends to result in the production of a second free radical which leads to proposed damage.

Question 2

What is superoxide?

Answer 2

This is an oxygen molecule with an extra electron. It is a source of other Reactive oxygen species and initiates free radical production.

Question 3

What is H2O2?

Answer 3

Hydrogen peroxide. This is not a reactive oxygen species, however it is highly reactive and leads to free radical formation. It breaks down into a hydroxyl radical and water.

Question 4

What is peroxynitrite and how is it formed?

Answer 4

ONOO-. It is formed from a nitric oxide radical and a superoxide molecule. It is not a free radical but is a powerful oxidant and so can cause damage to cells.

Question 5

State the two ways in which ROS can cause damage to DNA.

Answer 5

Damage to base - modified base leads to mis pairing and mutation.
Damage to sugar - causes strand to break, mutation on repair.

Question 6

Explain how ROS can lead to protein degradation.

Answer 6

ROS can cause damage to the backbone of protein molecules causes them to form fragments. This then leads to protein degradation.

Question 7

What happens when ROS react with protein side chains?

Answer 7

This can lead to a change in the folding of the protein. If this results in loss of function it will be degraded.

Question 8

What can affect disulphide bonds in proteins?

Answer 8

ROS can take an e- from one of the residues then this can lead to misfolding, cross linking and functional disruption.

Question 9

Explain what happens when an ROS interacts with a lipid.

Answer 9

Firstly it extracts a hydrogen atom from a polyunsaturated fatty acid. This then reacts with oxygen to for a lipidperoxyl radical. This then takes a hydrogen from a nearby fatty acid and a chain reaction begins.

Question 10

What is the consequence of a ROS interacting with a lipid in a phospholipid bilayer?

Answer 10

This decreases membrane integrity because the homophobic environment of the bilayer will be interrupted and a fatty streak may form – atherosclerosis.

Question 11

Give examples of exogenous biological oxidants.

Answer 11

Radiation, pollution, drugs and toxins.

Question 12

Give examples of endogenous biological oxidants

Answer 12

From electron transport chain, nitric oxide synthases, NADPH oxidases.

Question 13

Why is the electron transport chain at risk of producing biological oxidants.

Answer 13

Sometimes, electrons can escape from the chain and react with oxygen to give superoxide.

Question 14

Why do we have nitrogen oxide in the body?

Answer 14

In phagocytes this has a direct toxic effect. It is also used as a signalling molecule.

Question 15

What is respiratory burst?

Answer 15

Rapid release of superoxide and hydrogen peroxide by phagocytic cells to destroy invading bacteria.

Question 16

What is chronic granulomatous disease and what are the clinical consequences?

Answer 16

The problem with this disease is a genetic defect in NADPH oxidase complex and this leads to increased susceptibility to infections. NADPH oxidase complex is needed to produce superoxide from oxygen.

Question 17

Name two protective enzymes that protect cells from free radicals.

Answer 17

Superoxide dismutase and catalyse.

Question 18

What reaction does superoxide dismutase catalyse?

Answer 18

Superoxide –> hydrogen peroxide + oxygen

Question 19

In cellular defence, what is the enzyme which catalyses the reaction Hydrogen peroxide –> Water + Oxygen?

Answer 19

Catalyse.

Question 20

What is glutathione and what pathway is it reliant on?

Answer 20

Glutathione is synthesised by the body for protection against ROS. It relies on the pentose phosphate pathway to reduce the disulphide bond formed between two thiol groups so that they can continue to reduce hydrogen peroxide.

Question 21

What is the role of glutathione reductase?

Answer 21

This produces GSH from GSSG and in the process uses NADPH so that ROS can continue to be reduced.

Question 22

Hydrogen peroxide is converted to O2 at the same time as GSH –> GSSG. What enzyme catalyses this reaction?

Answer 22

Glutathione Perioxidase.

Question 23

What is the relationship between vitamin E and free radicals?

Answer 23

Vitamin E is a lipid soluble antioxidant which prevents against lipid peroxidation by removing lipid radicals. Vitamin C regenerates vitamin E so that it can continue to carry out this process.

Question 24

Explain the consequence of Glucose6phosphate dehydrogenase deficiency.

Answer 24

This means that there is a lack of NADPH meaning that we at more at risk of ROS damage including lipid peroxidation and protein damage.

Question 25

Why are red blood cells susceptible to oxidative damage? What happens?

Answer 25

Red blood cells are in an oxidative environment. the damage causes precipitates of haemoglobin to form called Heinz bodies. These bind to the cell membranes and this causes rigidity and so they cannot pass through capillaries.

Question 26

What is a clinical sign of G6PDH deficiency?

Answer 26

Blister cell presence. These are produced in the spleen when he is bodies are broken down which are caused as a result of oxidative damage.

Question 27

What is ischaemia reperfusion injury?

Answer 27

This is where an area has been ischaemic with no blood flow. On reintroduction of oxygen, incomplete metabolism leads to ROS but there are no antioxidants due to the ischaemia and so damage occurs.

Question 28

What is the problem with overdose of paracetamol?

Answer 28

With normal levels, paracetamol is broken down and excreted, however with high levels this causes it to enter other pathways which leads to the production of the intermediate NAPQI. This leads to oxidative damage of liver cells.

Question 29

What is the treatment for paracetamol overdose?

Answer 29

Acetyl cysteine. This replenishes stores of glutathione from NAPQI which have been depleted due to the increased oxidative stress from the toxic NAPQI.

Question 30

What is a free radical?

Answer 30

It is a substance with an unpaired electron which is capable of independent existence.