MEH: Oxidative Stress And Alcohol Metabolism

Question 1

Derive the metabolism of alcohol.

Answer 1

Ethanol is converted into acetaldehyde by the action of alcohol dehydrogenase. This is then converted into acetate by the action of aldehyde dehydrogenase.

Question 2

Where is most alcohol metabolised?

Answer 2

Liver

Question 3

How can the metabolism of alcohol cause damage to the liver?

Answer 3

• Accumulation of toxic acetaldehyde
• thee is an increase in Actetyl-CoA causing an increases in the synthesis of fatty acids and ketone bodies
• Increased synthesis of triacylglycerol
• This results in a fatty liver

Question 4

What drug can be used in the treatment of alcoholics?

Answer 4

Disulfiram

Question 5

How does disulfiram work?

Answer 5

• Inhibits aldehyde dehydrogenase
• If a patient drinks alcohol, acetaldehyde will build up causing the symptoms of a hanger over
• This is therefore a deterrent

Question 6

How are superoxide radicals produced by mitochondria?

Answer 6

During the ETC, occasionally electrons can accidentally escape the chain and react with dissolved oxygen to for superoxide.

Question 7

Name 4 cellular defences against oxidative stress.

Answer 7

1. SOD (Superoxide dismutase)- coverts superoxide into H2O2 and oxygen
2. Catalase- converts H2O2 into oxygen and water
3. Glutathione- donates e- to ROS. 2 of the oxidised form then form disulphide bonds.
4. Vit E and C- protection against lipid oxidative stress

Question 8

What is the role of oxidative stress in galactosaemia?

Answer 8

• Increased activity of aldose reductase consumes excess NADPH
• This compromises defences against ROS damage
• Crystalline protein in lens of eye becomes denatured

Question 9

What are Heinz bodies?

Answer 9

• A clinical sign of G6PDH

- Dark staining within red blood cells resulting from precipitated haemoglobin

Question 10

What is the role of oxidative stress in G6PDH?

Answer 10

• Decrease in G6PDH in the pentose pathway limits the amount of NADPH produced
• Lower glutathione means less protection from oxidative stress
• This is because NADPH is required for reduction of oxidative glutathione (GSSG) Na k go reduced glutathione (GSH)

Question 11

What is the problem with metabolism of paracetamol at high concentrations?

Answer 11

• Toxic NAPQI accumulates
• This means the body uses glutathione to neutralise this toxic substance - However this results in depleted glutathione which leaves the cell open to oxidative stress

Question 12

How is paracetamol overdoes treated?

Answer 12

Acetylcysteine- works by replenishing glutathione levels.