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

# Medium-chain acyl-CoA dehydrogenase (MCAD)

MCAD carries out the first β-oxidation step for fatty acids of 6 to 12 carbons; its lack is the most common defect in the group.

Updated 2026-11-01

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## Key facts

- Tetrameric flavoprotein of the mitochondrial matrix; uses FAD and hands electrons to ETF.
- Acts on medium-chain acyl-CoA (C6–C12), most active on octanoyl-CoA (C8).
- Family: VLCAD (very long chain, membrane-bound), LCAD, MCAD and SCAD (short).
- Most frequent variant in people of European ancestry: c.985A>G (p.Lys329Glu).

**Also called**
ACADM

**EC number**
[1.3.8.7](https://www.enzyme-database.org/query.php?ec=1.3.8.7)

**Genes**
ACADM

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

## Regulation

- Its expression rises during fasting via PPARα.
- No major allosteric control; it follows substrate flow.

## Inhibitors and toxins

- MCPA-CoA, a metabolite of ackee hypoglycin A

## Clinical notes

- MCAD deficiency: hypoketotic hypoglycaemia, vomiting and lethargy with fasting or infection; high octanoylcarnitine (C8) on screening.
- Ackee poisoning inhibits MCAD and SCAD and mimics the picture.

## Pathways

- [Fatty acid β-oxidation](https://durgical.com/en/biochemistry/pathways/fatty-acid-oxidation/)

## Related conditions

- [Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency](https://durgical.com/en/conditions/medium-chain-acyl-coa-dehydrogenase-deficiency/)
- [Jamaican vomiting sickness (ackee poisoning)](https://durgical.com/en/conditions/jamaican-vomiting-sickness/)

## Related

- [Carnitine palmitoyltransferase I (CPT-I)](https://durgical.com/en/biochemistry/enzymes/carnitine-palmitoyltransferase-i/)
- [Carnitine (L-carnitine)](https://durgical.com/en/biochemistry/molecules/carnitine/)
- [Acetyl-CoA](https://durgical.com/en/biochemistry/molecules/acetyl-coa/)
- [β-Hydroxybutyrate](https://durgical.com/en/biochemistry/molecules/hydroxybutyrate/)

## Test yourself

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

## Which acylcarnitine is raised in MCAD deficiency?

Octanoylcarnitine (C8), together with C6 and C10:1.

## Which coenzyme does MCAD use and where do its electrons go?

FAD; it passes them to electron transfer flavoprotein (ETF) and then to ubiquinone.

## Which natural toxin inhibits MCAD?

MCPA-CoA, derived from hypoglycin A in unripe ackee fruit.

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

Sources: [ACADM: Medium-chain specific acyl-CoA dehydrogenase, mitochondrial (human)](https://www.uniprot.org/uniprotkb/P11310/entry) (UniProt, 2026); [ACADM gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/acadm/) (MedlinePlus, US National Library of Medicine, 2026); [1EGC: Structure of T255E, E376G mutant of human medium chain acyl-CoA dehydrogenase complexed with octanoyl-CoA](https://www.rcsb.org/structure/1EGC) (RCSB Protein Data Bank, 2026).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/biochemistry/enzymes/medium-chain-acyl-coa-dehydrogenase/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/biochemistry/enzymes/medium-chain-acyl-coa-dehydrogenase/