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discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
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MetaCyc Enzyme: squalene monooxygenase

Gene: SQLE Accession Number: HS02595 (MetaCyc)

Synonyms: squalene epoxidase, squalene-2,3-epoxidase

Species: Homo sapiens

Summary:
A human liver cDNA was isolated that contained an open reading frame of 574 amino acids, corresponding to a protein with a molecular mass of 63,927 Da. It was 84% identical to rat and mouse enzymes. It was identified as a flavoprotein monooxygenase [Laden00].

Comment from LocusLink [Pruitt01]: Squalene epoxidase; enzyme of the sterol biosynthetic pathway. Summary: Squalene epoxidase catalyzes the first oxygenation step in sterol biosynthesis and is thought to be one of the rate-limiting enzymes in this pathway.
Locuslink ID: (6713). Locus confirmed. Locus status: REVIEWED. Locus evidence: supported by alignment with mRNA.

Citations: [Nagai02, Nagai97, Nakamura96a]

Locations: endoplasmic reticulum

Map Position: [126,015,909 -> 126,039,003]

Unification Links: ArrayExpress:Q14534 , Entrez-gene:6713 , PhosphoSite:Q14534 , Pride:Q14534 , Protein Model Portal:Q14534 , SMR:Q14534 , String:9606.ENSP00000265896 , UniProt:Q14534

Relationship Links: InterPro:IN-FAMILY:IPR001327 , InterPro:IN-FAMILY:IPR003042 , InterPro:IN-FAMILY:IPR013698 , Pfam:IN-FAMILY:PF00070 , Pfam:IN-FAMILY:PF08491 , Prints:IN-FAMILY:PR00420

Gene-Reaction Schematic: ?

GO Terms:

Biological Process: GO:0022900 - electron transport chain
Cellular Component: GO:0005783 - endoplasmic reticulum [Reinhart87]


Enzymatic reaction of: squalene,NADPH:oxygen oxidoreductase (2,3-epoxidizing) (squalene monooxygenase)

EC Number: 1.14.13.132

squalene + NADPH + oxygen + H+ <=> (3S)-2,3-epoxy-2,3-dihydrosqualene + NADP+ + H2O

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is physiologically favored in the direction shown.

In Pathways: superpathway of cholesterol biosynthesis , cholesterol biosynthesis I , cholesterol biosynthesis II (via 24,25-dihydrolanosterol) , cholesterol biosynthesis III (via desmosterol) , epoxysqualene biosynthesis

Summary:
A truncated form of this enzyme lacking the first 110 amino acids was expressed in E. coli, purified and characterized. The Kcat for squalene was 1.1 pmol/min/pmol. The Km for FAD was 0.3 μM. IC50s for tellurite and selenite were 17 μM and 37 μM, respectively. The enzyme was dependent upon coupling with NADPH-cytochrome P450 reductase for reducing equivalents [Laden00].

Cofactors or Prosthetic Groups: FAD [Laden00]

Inhibitors (Noncompetitive): selenite [Laden00] , tellurite [Laden00]

Kinetic Parameters:

Substrate
Km (μM)
Citations
squalene
7.7
[Laden00]

Exons/Introns:


References

Laden00: Laden BP, Tang Y, Porter TD (2000). "Cloning, heterologous expression, and enzymological characterization of human squalene monooxygenase." Arch Biochem Biophys 374(2);381-8. PMID: 10666321

Nagai02: Nagai M, Sakakibara J, Nakamura Y, Gejyo F, Ono T (2002). "SREBP-2 and NF-Y are involved in the transcriptional regulation of squalene epoxidase." Biochem Biophys Res Commun 295(1);74-80. PMID: 12083769

Nagai97: Nagai M, Sakakibara J, Wakui K, Fukushima Y, Igarashi S, Tsuji S, Arakawa M, Ono T (1997). "Localization of the squalene epoxidase gene (SQLE) to human chromosome region 8q24.1." Genomics 44(1);141-3. PMID: 9286711

Nakamura96a: Nakamura Y, Sakakibara J, Izumi T, Shibata A, Ono T (1996). "Transcriptional regulation of squalene epoxidase by sterols and inhibitors in HeLa cells." J Biol Chem 271(14);8053-6. PMID: 8626488

Pruitt01: Pruitt KD, Maglott DR (2001). "RefSeq and LocusLink: NCBI gene-centered resources." Nucleic Acids Res 29(1);137-40. PMID: 11125071

Reinhart87: Reinhart MP, Billheimer JT, Faust JR, Gaylor JL (1987). "Subcellular localization of the enzymes of cholesterol biosynthesis and metabolism in rat liver." J Biol Chem 262(20);9649-55. PMID: 3597431


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Thu Dec 18, 2014, BIOCYC13A.