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[Biochemistry](https://durgical.com/en/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.

**Also called**
Mitochondrial aldehyde dehydrogenase

**EC number**
[1.2.1.3](https://www.enzyme-database.org/query.php?ec=1.2.1.3)

**Genes**
ALDH2

**Structure (PDB)**
[2VLE](https://www.rcsb.org/structure/2VLE)

## 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

- [Disulfiram](https://durgical.com/en/pharmacology/disulfiram/)

## Pathways

- [Ethanol metabolism](https://durgical.com/en/biochemistry/pathways/ethanol-metabolism/)

## Related conditions

- [Disulfiram–ethanol reaction](https://durgical.com/en/conditions/disulfiram-ethanol-reaction/)
- [Oesophageal cancer](https://durgical.com/en/conditions/oesophageal-cancer/)
- [Alcoholic liver disease (biochemistry)](https://durgical.com/en/conditions/alcoholic-liver-disease/)

## Related

- [Alcohol dehydrogenase (ADH)](https://durgical.com/en/biochemistry/enzymes/alcohol-dehydrogenase/)
- [Acetaldehyde](https://durgical.com/en/biochemistry/molecules/acetaldehyde/)
- [Ethanol](https://durgical.com/en/biochemistry/molecules/ethanol/)
- [NAD⁺ (nicotinamide adenine dinucleotide)](https://durgical.com/en/biochemistry/molecules/nad/)
- [Reactive oxygen species and antioxidants](https://durgical.com/en/biochemistry/topics/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.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: [ALDH2: Aldehyde dehydrogenase, mitochondrial (human), UniProt P05091](https://www.uniprot.org/uniprotkb/P05091/entry) (UniProt, 2026); [RCSB PDB - 2VLE: The structure of daidzin, a naturally occurring anti alcohol- addiction agent, in complex with human mitochondrial aldehyde dehydrogenase](https://www.rcsb.org/structure/2VLE) (RCSB Protein Data Bank, 2026); [Alcohol use disorder: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/alcohol-use-disorder/) (MedlinePlus, US National Library of Medicine, 2026); [Disulfiram: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a682602.html) (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.

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/biochemistry/enzymes/aldehyde-dehydrogenase-2/