Alcohol dehydrogenase and Aldehyde dehydrogenase (ADH/ALDH)

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are the principal enzymes involved in the metabolic clearance of ethanol and other aliphatic alcohols (NIAAA, 2023). ADH catalyzes the oxidation of ethanol to acetaldehyde, a reactive and toxic electrophile, while ALDH subsequently oxidizes acetaldehyde to acetate, which can be utilized in the citric acid cycle (StatPearls, 2023). These enzymes are significant therapeutic targets in toxicology and psychiatry; for instance, ADH is inhibited by fomepizole to treat methanol or ethylene glycol poisoning by halting the production of toxic metabolites like formic acid or oxalic acid (StatPearls, 2023). Conversely, ALDH is targeted by disulfiram to treat alcohol use disorder, where enzyme inhibition leads to a rapid accumulation of acetaldehyde upon alcohol ingestion, causing a highly unpleasant physiological response known as the disulfiram-ethanol reaction (PubChem, 2024). Genetic polymorphisms in these enzymes, such as the ALDH2*2 variant, play a major role in individual alcohol sensitivity and the risk of developing alcohol-related malignancies, including esophageal cancer (Nature Reviews Disease Primers, 2017).

Other names

Alcohol:NAD+ oxidoreductaseAldehyde:NAD+ oxidoreductaseEthanol metabolism enzymesADHALDH

Alcohol dehydrogenase inhibitors prevent the conversion of alcohols into toxic aldehydes or acids, while aldehyde dehydrogenase inhibitors prevent the breakdown of acetaldehyde, leading to its accumulation and subsequent physiological distress.