squaleneepoxidase

Squalene epoxidase, also known as squalene monooxygenase, is an enzyme that initiates the oxygenation steps of sterol biosynthesis. With the enzyme commission number EC 1.14.99.7, it catalyzes the conversion of squalene to 2,3-oxidosqualene. The reaction is a flavin-dependent monooxygenation that uses molecular oxygen and electrons donated by NADPH, with a flavin adenine dinucleotide (FAD) cofactor facilitating the activation of oxygen.

The enzyme is typically a membrane-associated protein located in the endoplasmic reticulum of eukaryotic cells. It contains transmembrane regions that anchor it to the membrane, placing its active site on the cytosolic side where substrates and cofactors are accessible. The epoxidation of squalene is the first oxygenation step in sterol synthesis and is considered a rate-limiting step in many organisms.

Biological role and pathway context: The product, 2,3-oxidosqualene, is subsequently cyclized by oxidosqualene cyclase to form lanosterol, a key precursor that is converted into cholesterol in animals and ergosterol in fungi. In plants and other organisms, the pathway converges on similar sterol end products. Because SE sits upstream of essential sterol production, its activity influences membrane composition and cellular homeostasis.

Regulation and clinical relevance: Expression of the SQLE gene is regulated by sterol-dependent transcription factors and cellular cholesterol demands. Pharmacological inhibition of fungal squalene epoxidase—most notably by terbinafine—disrupts ergosterol synthesis and causes accumulation of squalene, forming the basis of a common antifungal therapy. Altered SE expression has also been observed in various diseases and is being explored as a therapeutic target in metabolic disorders and cancer.