Oxidative Stress

Question 1

What is superoxide?

Answer 1

O2.-

Question 2

How is NO useful?

Answer 2

Can damage pathogens

Question 3

List 3 cellular defences

Answer 3

Superoxide Dismutase & Catalase
Glutathione
Free radical scavengers

Question 4

Name some free radical scavengers and how they help defend cells?

Answer 4

Vitamin E, C

They donate a H+ and e- to the free radical without the need of enzymes

Question 5

How is vitamin C used to protect cells from damage?

Answer 5

Regenerates vitamin E which donates a H+ and e- to a free radical

Question 6

How do Superoxide Dismutase (SOD) & Catalase protect from oxidative damage?

Answer 6

SOD catalyses conversion of O2.- –> H2O2

Catalase converts H2O2–>2H2O + O2

Question 7

How does Glutathione protect cells from oxidative damage?

Answer 7

Reduced glutathione donates an e- from its think (SH) group to an ROS
Eg H2O2–>H2O

Question 8

Which enzyme converts/recycles oxidised glutathione to reduced?

Answer 8

Glutathione reductase

Question 9

Which enzyme converts reduced glutathione to oxidised?

Answer 9

Glutathione Peroxidase

Question 10

List some ROS and RNS

Answer 10

ROS- superoxide (O2-), H2O2, OH

RNS- NO., ONOO-

Question 11

What trace element does glutathione Peroxidase need?

Answer 11

Selenium

Question 12

What is peroxinitrite? ONOO-

Answer 12

Not technically a free radical but IS a powerful oxidant

Question 13

How can ROS damage DNA?

Answer 13

React with base to cause mispairing
React with sugar to break strand
Failure in repair causes mutations

Question 14

How can ROS’ damage proteins?

Answer 14

Modify the AA causing structure to change, gain or loss of function
Cause fragmentation
All of these lead to degradation of protein

Question 15

How can ROS’ damage lipids?

Answer 15

OH extracts H from unsaturated FA

Forms lipid radical which leads to lipid peroxidation

Question 16

How do oxidised fatty acids lead to atheromas?

Answer 16

Oxidised LDLs engulfed by macrophage
Macrophages accumulate in intima of blood vessel wall forming foam cells then fatty streak
Atherosclerotic plaque encroaches on lumen

Question 17

What is a measure of oxidative damage in cells?

Answer 17

8-oxo-dG

Modified nucleotide

Question 18

How are ROS formed?

Answer 18

During oxidative phosphorylation

Some e- don’t reach end ETC and so reduce O2 early

Question 19

Why is superoxide so dangerous?

Answer 19

Can activate other free radicals

Question 20

What order are ROS’ made?

Answer 20

O2–> O2.- –> H2O2–> .OH–> H2O

Question 21

What is the toxic metabolite that builds up in paracetamol metabolism?

Answer 21

NAPQI

N-acetyl-p-benzo-quinone imine

Question 22

What class of drug is paracetamol?

Answer 22

Anti-pyretic

Question 23

At safe levels, what is paracetamol metabolised to?

Answer 23

It is conjugated with glucoronide OR sulphate

Question 24

What is a toxic dose of paracetamol?

Answer 24

~10g

Question 25

Why is NAPQI so toxic to hepatocytes?

Answer 25

Metabolism of NAPQI uses up stores of Glutathione Then hepatocytes are more susceptible to oxidative damage Causes hepatocyte proteins to covalently bind

Question 26

What antidote is used for paracetamol overdose?

Answer 26

Acetylcysteine

Question 27

How does the antidote for paracetamol overdose work?

Answer 27

Replenishes glutathione source to allow liver to continue to metabolise paracetamol

Question 28

How does NAPQI directly cause damage?

Answer 28

NAPQI causes hepatic proteins to bind covalently with each other

Question 29

How does NAPQI indirectly cause damage to hepatocytes?

Answer 29

Conjugates with glutathione Uses up glutathione stores, leaves hepatocytes more susceptible to oxidative damage- eg lipid peroxidation, damage to DNA & proteins

Question 30

What oxidative damage does NAPQI cause?

Answer 30

Lipid peroxidation, damage to DNA & proteins

Question 31

What is NAPQI?

Answer 31

Strong oxidising agent, toxic metabolite of paracetamol metabolism

Question 32

How quickly should what antidote for paracetamol metabolism be administered?

Answer 32

Best- within 2 hours Still effective within 8 hours After death is inevitable due to liver failure

Question 33

Which is more important for oxidative damage- NADH or NADPH?

Answer 33

NADPH, it donates its H+/e- to oxidised glutathione to allow it to be recycled back to reduced Glutathione (GSH)