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

# Squalene epoxidase

Squalene epoxidase activates squalene with oxygen so it can close into rings; it is the second control point of cholesterol synthesis.

Updated 2026-11-01

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## Key facts

- Squalene + O₂ + NADPH → 2,3-oxidosqualene + H₂O; it uses FAD and gets electrons from cytochrome P450 reductase.
- It sits in the endoplasmic reticulum membrane.
- It is the second control point after HMG-CoA reductase: cholesterol speeds its degradation.
- Terbinafine inhibits the enzyme of fungi, which make ergosterol, and barely affects the human one.

**Also called**
Squalene monooxygenase (SQLE)

**EC number**
[1.14.14.17](https://www.enzyme-database.org/query.php?ec=1.14.14.17)

**Genes**
SQLE

**Structure (PDB)**
[6C6P](https://www.rcsb.org/structure/6C6P)

## Structure

- A 574-residue flavoprotein with an FAD-binding and a substrate-binding domain, attached to the membrane.
- Structure 6C6P shows the human catalytic domain with FAD and the inhibitor NB-598 in the substrate pocket.

## Regulation

- Cholesterol promotes its ubiquitination by MARCHF6 and its degradation.
- SREBP-2 raises its transcription.

## Inhibitors and toxins

- Allylamines: terbinafine, naftifine (antifungals)
- NB-598 (experimental)

## Clinical notes

- Terbinafine treats onychomycosis and tinea: the fungus builds up toxic squalene and runs out of ergosterol.
- SQLE is increased in some tumours and is studied as a cancer target.

## Pathways

- [Cholesterol synthesis (mevalonate pathway)](https://durgical.com/en/biochemistry/pathways/cholesterol-synthesis/)

## Related

- [Squalene](https://durgical.com/en/biochemistry/molecules/squalene/)
- [Lanosterol](https://durgical.com/en/biochemistry/molecules/lanosterol/)
- [HMG-CoA reductase](https://durgical.com/en/biochemistry/enzymes/hmg-coa-reductase/)
- [Cholesterol](https://durgical.com/en/biochemistry/molecules/cholesterol/)

## Test yourself

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

## What reaction does squalene epoxidase catalyse?

It turns squalene into 2,3-oxidosqualene using O₂, NADPH and FAD.

## Why does terbinafine kill the fungus without much harm to the person?

It is far more potent on the fungal squalene epoxidase; the fungus accumulates squalene and lacks ergosterol.

## What makes it a second control point of the pathway?

Cholesterol speeds its degradation and SREBP-2 controls its transcription.

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

Sources: [SQLE: Squalene monooxygenase (human)](https://rest.uniprot.org/uniprotkb/Q14534.txt) (UniProt, 2026); [6C6P: Human squalene epoxidase (SQLE, squalene monooxygenase) structure with FAD and NB-598](https://www.rcsb.org/structure/6C6P) (RCSB Protein Data Bank, 2026); [Cholesterol biosynthesis (R-HSA-191273)](https://reactome.org/PathwayBrowser/#/R-HSA-191273) (Reactome, 2026).

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Representative model, for educational purposes only.

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