By Dr. Maddie Swannack

Next Lesson - Oxidative Stress

Metabolism

Contents

  1. Alcohol
  2. Liver Damage
  3. Disulfiram
  4. Quiz

Abstract

  • Alcohol (ethanol) is a molecule with a high energy content (about 7 calories per gram) that is metabolised mainly by enzymes in the liver.
  • The rate-limiting step (the slowest step, which sets the speed of the whole pathway) in alcohol metabolism is usually alcohol dehydrogenase, the enzyme that converts alcohol to acetaldehyde (a toxic intermediate).
  • Drinking excess alcohol exposes the body to acetaldehyde. This is thought to be one of several contributors to a hangover in the short term (inflammation is another) and to liver damage in the long term.
  • Acetaldehyde build-up can be exploited when treating alcohol dependence. The drug disulfiram inhibits aldehyde dehydrogenase (the enzyme that breaks acetaldehyde down), so drinking alcohol while taking it causes an unpleasant reaction that can be severe. 

Core

Alcohol

Alcohol has more energy than carbohydrate (about 7 calories per gram, compared with 4). The liver burns alcohol in preference to fat, so less fat is used for energy and more is stored. Drinking excess alcohol can therefore lead to excess fat in the body, including fat in the liver.

Alcohol is measured in units instead of grams, and 1 unit in the UK contains 8 g (10 ml) of pure alcohol. Men and women are advised not to drink more than 14 units a week on a regular basis. Anyone who regularly drinks as much as 14 units a week should spread this over 3 or more days.

Over 90% of alcohol consumed is oxidised in the liver by the pathway in the diagram below:

 

Alcohol Metabolism Diagram SimpleMed

Diagram - The process of alcohol metabolism

SimpleMed original by Dr. Maddie Swannack

 

Alcohol dehydrogenase is usually the rate-limiting step in ethanol metabolism. When alcohol intake is high, acetaldehyde can accumulate because its conversion to acetate cannot keep pace.

Liver damage can also occur if there is inadequate NAD+, as when acetate builds up it can cause lactic acidosis, gout, hypoglycaemia and cirrhosis. This relates to glutathione and oxidative stress.

Disulfiram is an inhibitor of aldehyde dehydrogenase and is used to treat alcoholism. Drinking alcohol when taking disulfiram causes a build-up of acetaldehyde. This produces the disulfiram-alcohol reaction: flushing, nausea, palpitations (awareness of the heartbeat) and low blood pressure. The reaction can be severe and life-threatening, with arrhythmias (abnormal heart rhythms), respiratory depression (slow, shallow breathing) and coma. Even small amounts of alcohol, such as in perfume, aerosol sprays or low-alcohol drinks, can trigger it. The expectation of this reaction discourages the person from drinking, so disulfiram can help them stay abstinent. This is often described as classical conditioning (learning to link alcohol with feeling ill), but a review suggests the effect comes from the person's expectation of a reaction rather than from the reaction itself.

 

Edited by: Dr. Ben Appleby

Reviewed by: Dr. Thomas Burnell and Dr. Marcus Judge

Quiz

Preview the Alcohol Metabolism quiz

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