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 performs the same task.[7]
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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 production of 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.
Squalene epoxidase also catalyzes the formation of diepoxysqualene (DOS). DOS is converted to 24(S),25-epoxylanosterol by lanosterol synthase.
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This article incorporates text from the United States National Library of Medicine, which is in the public domain.
