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[Biochemistry](https://durgical.com/en/biochemistry/) · Enzyme

# ALA dehydratase

ALA dehydratase joins two ALA into the first pyrrole ring; it is the enzyme most sensitive to lead.

Updated 2026-11-01

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## Key facts

- 2 ALA → porphobilinogen + 2 H₂O, in the cytosol.
- It is an octamer with zinc in the active site; lead displaces the zinc and inactivates it.
- There is far more activity than needed: much can be lost without symptoms, except with lead or severe inherited deficiency.
- Its inhibition builds up ALA (not porphobilinogen) in blood and urine.

**Also called**
Porphobilinogen synthase

**EC number**
[4.2.1.24](https://www.enzyme-database.org/query.php?ec=4.2.1.24)

**Genes**
ALAD

**Structure (PDB)**
[1E51](https://www.rcsb.org/structure/1E51)

## Regulation

- It is not a control point of the pathway; its activity depends on available zinc.

## Inhibitors and toxins

- Lead (Pb²⁺)
- Succinylacetone, which builds up in tyrosinemia type I

## Clinical notes

- Lead poisoning: high urine ALA with normal porphobilinogen, plus high zinc protoporphyrin.
- ALA dehydratase deficiency porphyria (Doss) is autosomal recessive and very rare; it causes acute attacks like acute intermittent porphyria.
- In tyrosinemia type I, succinylacetone inhibits this enzyme and causes porphyria-like neurological crises.

## Pathways

- [Heme synthesis](https://durgical.com/en/biochemistry/pathways/heme-synthesis/)

## Related conditions

- [Lead poisoning](https://durgical.com/en/conditions/lead-poisoning/)
- [Acute intermittent porphyria](https://durgical.com/en/conditions/acute-intermittent-porphyria/)

## Related

- [δ-Aminolevulinic acid (ALA)](https://durgical.com/en/biochemistry/molecules/aminolevulinic-acid/)
- [Porphobilinogen](https://durgical.com/en/biochemistry/molecules/porphobilinogen/)
- [ALA synthase](https://durgical.com/en/biochemistry/enzymes/ala-synthase/)
- [Porphobilinogen deaminase](https://durgical.com/en/biochemistry/enzymes/porphobilinogen-deaminase/)

## Test yourself

Think of the answer, then tap the question to see it.

## Which metal does ALA dehydratase need, and which one inhibits it?

It needs zinc; lead displaces it and inhibits the enzyme.

## Which metabolite rises in urine when lead blocks ALA dehydratase?

δ-Aminolevulinic acid (ALA); porphobilinogen stays normal because it is made after the block.

## Which substance in tyrosinemia type I inhibits ALA dehydratase?

Succinylacetone; that is why these children can have porphyria-like neurological crises.

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

Sources: [ALAD: Delta-aminolevulinic acid dehydratase (human)](https://www.uniprot.org/uniprotkb/P13716/entry) (UniProt, 2026); [ALAD gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/alad/) (MedlinePlus, US National Library of Medicine, 2026); [1E51: Crystal structure of native human erythrocyte 5-aminolaevulinic acid dehydratase](https://www.rcsb.org/structure/1E51) (RCSB Protein Data Bank, 2026); [Lead poisoning: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/002473.htm) (MedlinePlus, US National Library of Medicine, 2026).

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Representative model, for educational purposes only.

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