Biochemistry · Enzyme
Aldehyde dehydrogenase 2 (ALDH2) !
A mitochondrial enzyme that clears the acetaldehyde made from alcohol; when it fails, drinking causes flushing, nausea and palpitations.
Updated 2026-11-01
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Key facts
- Acetaldehyde + NAD⁺ + H₂O → acetate + NADH + H⁺, in the mitochondrial matrix; it has a very low Km for acetaldehyde.
- It is a tetramer with a catalytic cysteine (Cys302) that attacks the aldehyde.
- The ALDH2*2 variant (Glu504Lys) is dominant negative; about a third of East Asian people carry it.
- Disulfiram blocks it irreversibly: the basis of aversive therapy for alcohol.
Structure
- Tetramer (dimer of dimers); each subunit has an NAD⁺-binding domain, a catalytic domain with Cys302 and an oligomerisation domain.
Regulation
- A single ALDH2*2 subunit in the tetramer is enough to cut activity sharply (dominant-negative effect).
- It also detoxifies aldehydes from lipid peroxidation (4-hydroxynonenal) and activates nitroglycerin.
Inhibitors and toxins
- Disulfiram (irreversible, through its metabolites)
- Daidzin (the one in the 3D structure)
- Cyanamide
- Some drugs cause disulfiram-like reactions (described with metronidazole and certain cephalosporins; the mechanism is debated)
Clinical notes
- ALDH2*2 carriers who drink have a higher risk of oesophageal cancer (acetaldehyde damages DNA).
- Nitroglycerin works less well in ALDH2*2 carriers, because ALDH2 converts it to nitric oxide.
- The 3D structure (2VLE) shows human ALDH2 with daidzin, an isoflavone that reduces alcohol intake in animals.
Drugs that act here
Pathways
Related conditions
Related
- Alcohol dehydrogenase (ADH)
- Acetaldehyde
- Ethanol
- NAD⁺ (nicotinamide adenine dinucleotide)
- Reactive oxygen species and antioxidants
Test yourself
Think of the answer, then tap the question to see it.
Which ALDH2 variant causes flushing with alcohol and why is it dominant?
ALDH2*2 (Glu504Lys): one faulty subunit is enough to inactivate almost the whole tetramer.
How does disulfiram work in alcohol dependence?
It inhibits ALDH2; on drinking, acetaldehyde builds up and causes very unpleasant symptoms.
Why do ALDH2*2 carriers who drink get more oesophageal cancer?
Because they accumulate acetaldehyde, which forms DNA adducts and is carcinogenic.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: ALDH2: Aldehyde dehydrogenase, mitochondrial (human), UniProt P05091 (UniProt, 2026); RCSB PDB - 2VLE: The structure of daidzin, a naturally occurring anti alcohol- addiction agent, in complex with human mitochondrial aldehyde dehydrogenase (RCSB Protein Data Bank, 2026); Alcohol use disorder: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Disulfiram: MedlinePlus Drug Information (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).
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Representative model, for educational purposes only.