Ethanol metabolism

Ethanol metabolism centres around its conversion to acetyl coenzyme A within the liver. As all the enzymes involved in this transition are in approximate equilibrium, the flux-generating step is the rate of supply of ethanol to the liver in portal blood.

There are 3 key enzyme systems converting ethanol to ethanal:

• alcohol dehydrogenase
• microsomal ethanol oxidizing system
• catalase

Ethanal is then converted to acetate by aldehyde dehydrogenase.

Aldehyde residues are then converted to acetyl-CoA by acetyl-CoA synthetase. Acetyl-CoA is then made available for:

• tricarboxylic acid cycle oxidation
• fatty acid synthesis
• triglyceride synthesis

Clinically, there are several points of relevance:

• metabolism of excessive amounts of alcohol requires excessive reduction of cellular NAD; this limits the reactions in gluconeogenesis dependent on NAD. Hypoglycaemia can result.
• testosterone synthesis is dependent on a favourable NAD/NADH ratio. Hence, reduced NAD may contribute to the changes of hypogonadism and gynaecomastia associated with high ethanol intake.
• acetaldehyde intermediates are toxic. Their accumulation with excessive ethanol intake can lead to hepatocyte necrosis.