squalene monooxygenase

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.

Inhibitors of squalene epoxidase have found application mainly as antifungal drugs:{{cite journal | vauthors = Favre B, Ryder NS | title = Characterization of squalene epoxidase activity from the dermatophyte Trichophyton rubrum and its inhibition by terbinafine and other antimycotic agents | journal = Antimicrobial Agents and Chemotherapy | volume = 40 | issue = 2 | pages = 443–7 | date = Feb 1996 | pmid = 8834895 | pmc = 163131 | doi = 10.1128/AAC.40.2.443}}

• butenafine
• naftifine
• terbinafine{{cite journal | vauthors = Ryder NS | title = Terbinafine: mode of action and properties of the squalene epoxidase inhibition | journal = The British Journal of Dermatology | volume = 126 | pages = 2–7 | date = Feb 1992 | issue = Suppl 39 | pmid = 1543672 | doi = 10.1111/j.1365-2133.1992.tb00001.x | s2cid = 19780957 }}

Since squalene epoxidase is on the biosynthetic pathway leading to production of cholesterol, inhibitors of this enzyme may also find application in treatment of hypercholesterolemia.{{cite journal | vauthors = Chugh A, Ray A, Gupta JB | title = Squalene epoxidase as hypocholesterolemic drug target revisited | journal = Progress in Lipid Research | volume = 42 | issue = 1 | pages = 37–50 | date = Jan 2003 | pmid = 12467639 | doi = 10.1016/S0163-7827(02)00029-2 }}

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.

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

• Antifungal drug#Allylamines

{{Clear}}

{{Reflist|33em}}

{{refbegin|33em}}

• {{cite journal | vauthors = Ma J, Dempsey AA, Stamatiou D, Marshall KW, Liew CC | title = Identifying leukocyte gene expression patterns associated with plasma lipid levels in human subjects | journal = Atherosclerosis | volume = 191 | issue = 1 | pages = 63–72 | date = Mar 2007 | pmid = 16806233 | doi = 10.1016/j.atherosclerosis.2006.05.032 }}
• {{cite journal | vauthors = Laden BP, Tang Y, Porter TD | title = Cloning, heterologous expression, and enzymological characterization of human squalene monooxygenase | journal = Archives of Biochemistry and Biophysics | volume = 374 | issue = 2 | pages = 381–8 | date = Feb 2000 | pmid = 10666321 | doi = 10.1006/abbi.1999.1629 }}
• {{cite journal | vauthors = Helms MW, Kemming D, Pospisil H, Vogt U, Buerger H, Korsching E, Liedtke C, Schlotter CM, Wang A, Chan SY, Brandt BH | title = Squalene epoxidase, located on chromosome 8q24.1, is upregulated in 8q+ breast cancer and indicates poor clinical outcome in stage I and II disease | journal = British Journal of Cancer | volume = 99 | issue = 5 | pages = 774–80 | date = Sep 2008 | pmid = 18728668 | pmc = 2528137 | doi = 10.1038/sj.bjc.6604556 }}
• {{cite journal | vauthors = Nagai M, Sakakibara J, Nakamura Y, Gejyo F, Ono T | title = SREBP-2 and NF-Y are involved in the transcriptional regulation of squalene epoxidase | journal = Biochemical and Biophysical Research Communications | volume = 295 | issue = 1 | pages = 74–80 | date = Jul 2002 | pmid = 12083769 | doi = 10.1016/S0006-291X(02)00623-X }}
• {{cite journal | vauthors = Liu Y, Sun W, Zhang K, Zheng H, Ma Y, Lin D, Zhang X, Feng L, Lei W, Zhang Z, Guo S, Han N, Tong W, Feng X, Gao Y, Cheng S | title = Identification of genes differentially expressed in human primary lung squamous cell carcinoma | journal = Lung Cancer | volume = 56 | issue = 3 | pages = 307–17 | date = Jun 2007 | pmid = 17316888 | doi = 10.1016/j.lungcan.2007.01.016 }}
• {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1–2 | pages = 149–56 | date = Oct 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}
• {{cite journal | vauthors = Lu Y, Dollé ME, Imholz S, van 't Slot R, Verschuren WM, Wijmenga C, Feskens EJ, Boer JM | title = Multiple genetic variants along candidate pathways influence plasma high-density lipoprotein cholesterol concentrations | journal = Journal of Lipid Research | volume = 49 | issue = 12 | pages = 2582–9 | date = Dec 2008 | pmid = 18660489 | doi = 10.1194/jlr.M800232-JLR200 | doi-access = free }}
• {{cite journal | vauthors = Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, Bechtel S, Simpson J, Hofmann O, Hide W, Glatting KH, Huber W, Pepperkok R, Poustka A, Wiemann S | title = The LIFEdb database in 2006 | journal = Nucleic Acids Research | volume = 34 | issue = Database issue | pages = D415-8 | date = Jan 2006 | pmid = 16381901 | pmc = 1347501 | doi = 10.1093/nar/gkj139 }}
• {{cite journal | vauthors = Hartley JL, Temple GF, Brasch MA | title = DNA cloning using in vitro site-specific recombination | journal = Genome Research | volume = 10 | issue = 11 | pages = 1788–95 | date = Nov 2000 | pmid = 11076863 | pmc = 310948 | doi = 10.1101/gr.143000 }}
• {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1–2 | pages = 171–4 | date = Jan 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
• {{cite journal | vauthors = Nakamura Y, Sakakibara J, Izumi T, Shibata A, Ono T | title = Transcriptional regulation of squalene epoxidase by sterols and inhibitors in HeLa cells | journal = The Journal of Biological Chemistry | volume = 271 | issue = 14 | pages = 8053–6 | date = Apr 1996 | pmid = 8626488 | doi = 10.1074/jbc.271.14.8053 | doi-access = free }}
• {{cite journal | vauthors = Nagai M, Sakakibara J, Wakui K, Fukushima Y, Igarashi S, Tsuji S, Arakawa M, Ono T | title = Localization of the squalene epoxidase gene (SQLE) to human chromosome region 8q24.1 | journal = Genomics | volume = 44 | issue = 1 | pages = 141–3 | date = Aug 1997 | pmid = 9286711 | doi = 10.1006/geno.1997.4825 }}
• {{cite journal | vauthors = Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A | title = From ORFeome to biology: a functional genomics pipeline | journal = Genome Research | volume = 14 | issue = 10B | pages = 2136–44 | date = Oct 2004 | pmid = 15489336 | pmc = 528930 | doi = 10.1101/gr.2576704 }}

{{refend}}

• {{MeshName|Squalene+monooxygenase}}

{{Ketone and cholesterol metabolism enzymes}}

{{Dioxygenases}}

{{Enzymes}}

{{Portal bar|Biology|border=no}}

{{NLM content}}

Category:EC 1.14.13