Alcohol metabolism

Question 1

How does metabolism of alcohol lead to a fatty liver? What does it then lead to?

Answer 1

acetyl CoA from acetate + CoA can be used in fatty acid synthesis (TCA cycle) causing fatty liver

fatty liver (can’t get rid of fat properly) –> hepatitis (inflame) –> cirrhosis (scarring)

Question 2

What happens if aldehyde dehydrogenase is absent?

Answer 2

causes acetaldehyde to accumulate within the body which is toxic

Question 3

At what rate is ethanol excreted from the body?

Answer 3

0 order for kinetics

linear rate: alcohol elimination from body

Question 4

How is ethanol metabolised?

Answer 4

alcohol –> acetaldehyde (alcohol dehydrogenase) NAD+ –> NADH

acetaldehyde –> acetate (aldehyde dehydrogenase) NAD+ –> NADH

acetate + CoA –> acetyl CoA

Question 5

How does body keep acetaldehyde levels low?

Answer 5

through aldehyde dehydrogenase which has a low Km (Vmax quickly reached)

Question 6

What does prolonged and excessive alcohol consumption cause?

Answer 6

accumulation of acetaldehyde

Question 7

What does accumulation of acetaldehyde lead to?

Answer 7

liver damage - fatty liver –> alcohol hepatitis (inflammation) –> alcohol cirrhosis (scarring)

Question 8

How does metabolism of excess alcohol cause damage to liver?

Answer 8

excess NADH & acetyl CoA produced (NAD+ required for step 6 of glycolysis) leading to changes in liver metabolism –> fatty liver - doesn’t get rid of fat properly - swollen with fat –> inflammation of liver (alcohol hepatitis) –> scarring of liver (alcohol cirrhosis)

Question 9

Explain the mechanism of action of disulfiram in the treatment of alcohol dependence

Answer 9

disulfiram inhibits aldehyde dehydrogenase
so when patient drinks alcohol, the acetaldehyde accumulates leading to a feeling of sick and hangover very quickly as the acetaldehyde is not broken down