Squalene monooxygenase

From Wikipedia, the free encyclopedia
Jump to navigation Jump to search
Squalene epoxidase
Squalene epoxide biosynthesis.png
Chemical reaction catalyzed by squalene epoxidase.
EC no.
CAS no.9029-62-3
IntEnzIntEnz view
ExPASyNiceZyme view
MetaCycmetabolic pathway
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
AliasesSQLE, entrez:6713, squalene epoxidase
External IDsOMIM: 602019 MGI: 109296 HomoloGene: 2355 GeneCards: SQLE
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr 8: 125 – 125.02 MbChr 15: 59.19 – 59.2 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse

Squalene monooxygenase (also called squalene epoxidase) is a eukaryotic enzyme that uses NADPH and diatomic oxygen to oxidize squalene to 2,3-oxidosqualene (squalene epoxide). Squalene epoxidase catalyzes the first oxygenation step in sterol biosynthesis and is thought to be one of the rate-limiting enzymes in this pathway.[5] In humans, squalene epoxidase is encoded by the SQLE gene.[6] Several eukaryote genomes lack a squalene monooxygenase encoding gene, but instead encode an alternative squalene epoxidase that preforms the same task.[7]


The canonical squalene monooxygenase is a flavoprotein monooxygenase. Flavoprotein monooxygenase form flavin hydroperoxides at the enzyme active site, which then transfer the terminal oxygen atom of the hydroperoxide to the substrate. Squalene monooxygenase differs from other flavin monooxygenases in that the oxygen is inserted into the substrate as an epoxide rather than as a hydroxyl group. This enzyme contains a loosely bound FAD flavin and obtains electrons from NADPH-cytochrome P450 reductase, rather than binding NADPH directly. The alternative squalene epoxidase belongs to the fatty acid hydroxylase superfamily and obtains electrons from cytochrome b5.[7]


Inhibitors of squalene epoxidase have found application mainly as antifungal drugs:[8]

Since squalene epoxidase is on the biosynthetic pathway leading to cholesterol, inhibitors of this enzyme may also find application in treatment of hypercholesterolemia.[10]


In baker's yeast (Saccharomyces cerevisiae), squalene epoxidase is localized to both the endoplasmic reticulum and lipid droplets. Only the ER localized protein is active.

Additional products[edit]

Squalene epoxidase also catalyzes the formation of diepoxysqualene (DOS). DOS is converted to 24(S),25-epoxylanosterol by lanosterol synthase.

Model organisms[edit]

Model organisms have been used in the study of SQLE function. A conditional knockout mouse line called Sqletm1a(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute.[11] Male and female animals underwent a standardized phenotypic screen[12] to determine the effects of deletion.[13][14][15][16] Additional screens performed: - In-depth immunological phenotyping[17]

See also[edit]


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000104549 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000022351 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "Entrez Gene: SQLE squalene epoxidase".
  6. ^ Nagai M, Sakakibara J, Wakui K, Fukushima Y, Igarashi S, Tsuji S, Arakawa M, Ono T (Aug 1997). "Localization of the squalene epoxidase gene (SQLE) to human chromosome region 8q24.1". Genomics. 44 (1): 141–3. doi:10.1006/geno.1997.4825. PMID 9286711.
  7. ^ a b Pollier J, Vancaester E, Kuzhiumparambil U, Vickers CE, Vandepoele K, Goossens A, Fabris M (2019). "A widespread alternative squalene epoxidase participates in eukaryote steroid biosynthesis". Nature Microbiology. 4 (2): 226–233. doi:10.1038/s41564-018-0305-5. hdl:1854/LU-8587985. PMID 30478288. S2CID 53726187.
  8. ^ Favre B, Ryder NS (Feb 1996). "Characterization of squalene epoxidase activity from the dermatophyte Trichophyton rubrum and its inhibition by terbinafine and other antimycotic agents". Antimicrobial Agents and Chemotherapy. 40 (2): 443–7. doi:10.1128/AAC.40.2.443. PMC 163131. PMID 8834895.
  9. ^ Ryder NS (Feb 1992). "Terbinafine: mode of action and properties of the squalene epoxidase inhibition". The British Journal of Dermatology. 126 Suppl 39: 2–7. doi:10.1111/j.1365-2133.1992.tb00001.x. PMID 1543672. S2CID 19780957.
  10. ^ Chugh A, Ray A, Gupta JB (Jan 2003). "Squalene epoxidase as hypocholesterolemic drug target revisited". Progress in Lipid Research. 42 (1): 37–50. doi:10.1016/S0163-7827(02)00029-2. PMID 12467639.
  11. ^ Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. S2CID 85911512.
  12. ^ a b "International Mouse Phenotyping Consortium".
  13. ^ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  14. ^ Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  15. ^ Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. S2CID 18872015.
  16. ^ White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP (Jul 2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell. 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.
  17. ^ a b "Infection and Immunity Immunophenotyping (3i) Consortium".

Further reading[edit]

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.