Oxidative Stress

Question 1

Define free radicals

Answer 1

An atom or molecule that contains one or more unpaired electron and is capable of ‘free’ existence.

Question 2

Which molecules is the free radical exception?

Answer 2

The molecular oxygen that we breathe. Has 2 unpaired electrons but not highly reactive to the same extent.

Question 3

Name the reactive nitrogen species

Answer 3

nitric oxide (NO.) and peroxynitrite (ONOO-)

Question 4

What is nitric oxide used for?

Answer 4

vasodilation and immune response in high concs

Question 5

What is the most reactive and damaging free radical?

Answer 5

Hydroxyl radical (OH.)

Question 6

Why is hydrogen peroxide dangerous?

Answer 6

readily diffusible and can react to produce very damaging free radicals

Question 7

How can ROS damage DNA?

Answer 7

react with base: mispairing and mutation

react with sugar: strand break and mutation on repair

Question 8

What is 8-oxo-dG used for?

Answer 8

Measurement of oxidative damage within the cell

Question 9

How can ROS damage proteins?

Answer 9

damage backbone: fragmentation and degradation

react with side chain: modified amino acids

Question 10

What can a change in protein structure cause?

Answer 10

gain of function, loss of function and degradation

Question 11

Where do disulfide bonds form?

Answer 11

Between thiol groups of cysteine residues

Question 12

What can inappropriate disulfide bond formation lead to?

Answer 12

misfolding, cross-linking, disruption of function

Question 13

How does ROS damage lipids?

Answer 13

free radical extract hydrogen atom from unsaturated FA, lipid radical formed, react with oxygen to produce a lipid peroxyl radical, chain reaction disrupts hydrophobic environment

Question 14

Name the endogenous oxidant sources

Answer 14

electron transport chain, nitric oxide synthases and NADPH oxidases

Question 15

Name the exogenous sources of oxidants

Answer 15

radiation, pollutants, drugs and toxins

Question 16

How many types of nitric oxide synthases are there and which one is most important?

Answer 16

3 types, iNOS is most important: oxidative burst in phagocytes

Question 17

What is an oxidative burst?

Answer 17

The rapid released of ROS and RNS from phagocytic cells to destroy invading bacteria.

Question 18

Which enzymes are important in oxidative burst?

Answer 18

NADPH oxidase, iNOS, myeloperoxidase

Question 19

Which enzymes work together as a cellular defence against oxidative damage?

Answer 19

superoxide dismutase and catalase

Question 20

What is the function of superoxide dismutase?

Answer 20

converts superoxide to hydrogen peroxide and oxygen and stops superoxide initiating a chain reaction

Question 21

Where is SOD expressed most?

Answer 21

In mitochondria to mop of superoxides from ETC

Question 22

What is the function of catalase?

Answer 22

converts hydrogen peroxide to water and oxygen and protects against oxidative burst

Question 23

How does glutathione work?

Answer 23

thiol group of Cys residue donates electron to ROS, two GSHs react to form GSSG via the enzyme glutathione peroxidase

Question 24

How is GSSG reduced back to GSH?

Answer 24

glutathione reductase, transfers electrons from NADPH to disulfide bond to break it

Question 25

Which vitamins are free radical scavengers?

Answer 25

vitamin E and vitamin C

Question 26

How do vitamins protect against oxidative damage?

Answer 26

vitamin E is oxidised to prevent lipids being oxidised and vitamin C regenerates the reduced formed of vitamin E

Question 27

Do for vitamins require enzymes to protect against oxidative damage?

Answer 27

No | The reactions are non-enzymatic

Question 28

Name 2 other free radical scavengers

Answer 28

uric acid and melatonin

Question 29

What happens in galactosaemia that makes the patient susceptible to oxidative damage?

Answer 29

increased activity of aldose reductase, more NADPH consumed, less NADPH available to reduce glutathione (GSSG), compromised defence against ROS

Question 30

Which enzymes can be deficient in galactosaemia?

Answer 30

galactokinase, galactose-1-P uridyl transferase, UDP-galactose-epimerase

Question 31

How could G6PDH deficiency affect oxidative stress?

Answer 31

less pentose phosphate pathway, limits amount of NADPH produced, less NADPH available for reducing glutathione, more susceptible to oxidative damage

Question 32

How is paracetamol normally metabolised?

Answer 32

Safely metabolised through conjugation with sulphate or glucuronide

Question 33

What usually reduces the effects of NAPQI?

Answer 33

Glutathione

Question 34

How does N-acetylcysteine work?

Answer 34

It boosts glutathione levels so cells are less susceptible to oxidative damage and levels of NAPQI can be reduced.

Question 35

What is ischaemia reperfusion injury?

Answer 35

Reperfusion of oxygenated blood after ischaemia that results in more damage.

Question 36

Why does the reperfusion injury occur?

Answer 36

ROS are produced due to incomplete metabolism and antioxidants are lost in ischaemia

Question 37

Name some diseases that can result from oxidative stress

Answer 37

multiple sclerosis, Parkinson's, cancer, rheumatoid arthritis, COPD, pancreatitis