Lecture 33: Alcohol metabolism

Question 1

How is ethanol oxidised to acetate?

Where does this process occur?

What enzymes are involved?

Answer 1

Ethanol is oxidised by enzymes in the liver

• alcohol dehydrogenase catalysed the first rate-limiting step and is present in the cytosol of the liver
• the oxidation of ethanol generates acetaldehyde which is highly toxic
• acetaldehyde is then oxidised to acetate and is catalysed by aldehyde dehydrogenase

Question 2

Write the reactions for the conversion of ethanol to acetate

Answer 2

ethanol ——-> acetaldehyde

• enzyme = alcohol dehydrogenase
• NAD+(reduced form) is oxidised to NADH(oxidised form)

acetaldehyde ——–> acetate

• enzyme = aldehyde dehydrogenase
• NAD+ is oxidised to NADH in the process

Question 3

How is acetate further metabolised?

Where does this occur?

Answer 3

Acetate can further be metabolised in the liver, brain, heart and skeletal muscle

• acetate must be converted to acetyl-CoA to further be metabolised
• acetate is converted to acetyl-CoA, this reaction is catalysed by acetyl-CoA synthase and requires ATP

Question 4

What happens to the acetyl-CoA after it has been activated?

Answer 4

Acetyl-CoA can then be oxidised by the citric acid cycle which produces NADH and FADH2 - the conserved energy in these coenzymes is used at the electron transport chain
- by the transfer of electrons to O2, the conserved energy is used to drive the synthesis of ATP from ADP and Pi

Question 5

What are the consequences of ethanol metabolism ?

Answer 5

• ethanol metabolism produces large quantities of acetyl-CoA, NADH and ATP
• ATP and NADH slow electron transport and the citric acid cycle citrate levels rise
• slows down glucose metabolism by inhibiting phosphofructokinase and pyruvate dehydrogenase.
• slows down glycolysis
• impairment of fatty oxidation
• steatosis = accumulation of fat in the liver

Question 6

How can alcohol be metabolised as a toxin?

Answer 6

Ethanol can be treated as a toxin rather than a fuel - pathway is called microsomal p450 ethanol systems MEOS
- acetaldehyde is toxic —–> fatty liver/inflammation —–> alcohol hepatitis —-> necrosis —–> cirrhosis —-> coma and death