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

# ALA synthase

ALA synthase opens and controls heme synthesis: it joins glycine and succinyl-CoA in the mitochondrion.

Updated 2026-11-01

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## Key facts

- Glycine + succinyl-CoA → δ-aminolevulinic acid (ALA) + CoA + CO₂; the rate-limiting step of the pathway.
- It needs pyridoxal phosphate (vitamin B6) bound to an active-site lysine.
- ALAS1 (chromosome 3) is in every cell and is repressed by heme; ALAS2 (X chromosome) is erythroid and is controlled by iron.
- It is made in the cytosol and imported into the mitochondrial matrix; heme blocks that import.

**Also called**
δ-aminolevulinate synthase, ALAS1 (liver), ALAS2 (erythroid)

**EC number**
[2.3.1.37](https://www.enzyme-database.org/query.php?ec=2.3.1.37)

**Genes**
ALAS1, ALAS2

**Structure (PDB)**
[6HRH](https://www.rcsb.org/structure/6HRH)

## Regulation

- ALAS1: heme represses its gene, speeds up decay of its mRNA and blocks its mitochondrial import.
- ALAS1 rises with P450-inducing drugs, fasting (via PGC-1α), alcohol and steroid hormones.
- ALAS2: its mRNA has a 5' IRE; without iron, IRP binds it and stops translation.

## Inhibitors and toxins

- Heme and hemin (ALAS1 repression)
- Givosiran: an interfering RNA that silences liver ALAS1
- Isoniazid, indirectly, by depleting vitamin B6

## Clinical notes

- Acute porphyria attacks are triggered when something induces ALAS1 (drugs, fasting, progesterone); treatment aims to switch it off (hemin, glucose, givosiran).
- Loss-of-function ALAS2 mutations cause X-linked sideroblastic anemia, which sometimes improves with vitamin B6.
- Gain-of-function ALAS2 mutations make excess protoporphyrin: X-linked protoporphyria, similar to the erythropoietic form.

## Pathways

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

## Related conditions

- [Acute intermittent porphyria](https://durgical.com/en/conditions/acute-intermittent-porphyria/)
- [Erythropoietic protoporphyria](https://durgical.com/en/conditions/erythropoietic-protoporphyria/)

## Related

- [δ-Aminolevulinic acid (ALA)](https://durgical.com/en/biochemistry/molecules/aminolevulinic-acid/)
- [ALA dehydratase](https://durgical.com/en/biochemistry/enzymes/ala-dehydratase/)
- [Heme](https://durgical.com/en/biochemistry/molecules/heme/)
- [Iron metabolism](https://durgical.com/en/biochemistry/topics/iron-metabolism/)
- [Krebs cycle (citric acid cycle)](https://durgical.com/en/biochemistry/pathways/krebs-cycle/)

## Test yourself

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

## Which vitamin is the cofactor of ALA synthase?

B6, as pyridoxal phosphate; its deficiency can cause sideroblastic anemia.

## Which ALA synthase isoform is regulated by iron, and which by heme?

Iron regulates ALAS2 (erythroid) through an IRE in its mRNA; heme represses ALAS1 (liver).

## Why can fasting trigger an acute porphyria attack?

Fasting activates PGC-1α, which induces ALAS1 and raises production of ALA and porphobilinogen.

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

Sources: [ALAS2: 5-aminolevulinate synthase, erythroid-specific, mitochondrial (human)](https://www.uniprot.org/uniprotkb/P22557/entry) (UniProt, 2026); [ALAS1: 5-aminolevulinate synthase, non-specific, mitochondrial (human)](https://www.uniprot.org/uniprotkb/P13196/entry) (UniProt, 2026); [ALAS2 gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/alas2/) (MedlinePlus, US National Library of Medicine, 2026); [6HRH: Structure of human erythroid-specific 5'-aminolevulinate synthase, ALAS2](https://www.rcsb.org/structure/6HRH) (RCSB Protein Data Bank, 2026).

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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/ala-synthase/