Squalene monooxygenase

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Squalene epoxidase
Cholesterol-Synthesis-Reaction11.png
Chemical reaction catalyzed by squalene epoxidase.
Identifiers
EC number 1.14.13.132
CAS number 9029-62-3
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO
Squalene epoxidase
Identifiers
Symbols SQLE ; FLJ30795
External IDs OMIM602019 MGI109296 HomoloGene2355 IUPHAR: 2433 ChEMBL: 3592 GeneCards: SQLE Gene
EC number 1.14.13.132
Orthologs
Species Human Mouse
Entrez 6713 20775
Ensembl ENSG00000104549 ENSMUSG00000022351
UniProt Q14534 P52019
RefSeq (mRNA) NM_003129 NM_009270
RefSeq (protein) NP_003120 NP_033296
Location (UCSC) Chr 8:
126.01 – 126.03 Mb
Chr 15:
59.32 – 59.33 Mb
PubMed search [1] [2]

Squalene monooxygenase is an enzyme that uses NADPH and molecular 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.[1] In humans, squalene epoxidase is encoded by the SQLE gene.[2] Squalene monooxygenase (SqMO) was formerly referred to as squalene epoxidase (SqE) in the literature. [3]

Mechanism[edit]

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 as an epoxide rather than as a hydroxyl group. Squalene monooxygenase contains a loosely bound FAD flavin and obtains electrons from NADPH-cytochrome P450 reductase, rather than binding the nicotinamide cofactor NADPH directly.

Inhibitors[edit]

Inhibitors of squalene epoxidase have found application mainly as antifungal drugs:[4]

Since squalene epoxidase is on the biosynthetic pathway leading to cholesterol, inhibitors of this enzyme may also find application in treatment of hypercholesterolemia.[6]

Localization[edit]

In 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.

See also[edit]


References[edit]

  1. ^ "Entrez Gene: SQLE squalene epoxidase". 
  2. ^ Nagai M, Sakakibara J, Wakui K, Fukushima Y, Igarashi S, Tsuji S et al. (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. 
  3. ^ Sharpe LJ, Brown AJ (Jun 2013). "Controlling cholesterol synthesis beyond 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR)". The Journal of Biological Chemistry 288 (26). doi:10.1074/jbc.R113.479808. PMID 23696639. 
  4. ^ 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. PMC 163131. PMID 8834895. 
  5. ^ 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. 
  6. ^ 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. 

Further reading[edit]

External links[edit]

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