Oxidative Stress Flashcards

1
Q

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

A

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

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2
Q

What is superoxide?

A

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

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3
Q

What is H2O2?

A

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.

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4
Q

What is peroxynitrite and how is it formed?

A

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.

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5
Q

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

A

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

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6
Q

Explain how ROS can lead to protein degradation.

A

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

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7
Q

What happens when ROS react with protein side chains?

A

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

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8
Q

What can affect disulphide bonds in proteins?

A

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

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9
Q

Explain what happens when an ROS interacts with a lipid.

A

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.

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10
Q

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

A

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

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11
Q

Give examples of exogenous biological oxidants.

A

Radiation, pollution, drugs and toxins.

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12
Q

Give examples of endogenous biological oxidants

A

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

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13
Q

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

A

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

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14
Q

Why do we have nitrogen oxide in the body?

A

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

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15
Q

What is respiratory burst?

A

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

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16
Q

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

A

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.

17
Q

Name two protective enzymes that protect cells from free radicals.

A

Superoxide dismutase and catalyse.

18
Q

What reaction does superoxide dismutase catalyse?

A

Superoxide –> hydrogen peroxide + oxygen

19
Q

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

A

Catalyse.

20
Q

What is glutathione and what pathway is it reliant on?

A

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.

21
Q

What is the role of glutathione reductase?

A

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

22
Q

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

A

Glutathione Perioxidase.

23
Q

What is the relationship between vitamin E and free radicals?

A

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.

24
Q

Explain the consequence of Glucose6phosphate dehydrogenase deficiency.

A

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.

25
Q

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

A

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.

26
Q

What is a clinical sign of G6PDH deficiency?

A

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.

27
Q

What is ischaemia reperfusion injury?

A

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.

28
Q

What is the problem with overdose of paracetamol?

A

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.

29
Q

What is the treatment for paracetamol overdose?

A

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

30
Q

What is a free radical?

A

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