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.
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