Cytochrome P450 11A1 (CYP11A1)

Cytochrome P450 11A1 (CYP11A1), also known as cholesterol side-chain cleavage enzyme (P450scc), is a mitochondrial monooxygenase that catalyzes the first and rate-limiting step in the biosynthesis of all steroid hormones [1, 2]. It is responsible for the conversion of cholesterol into pregnenolone through three sequential oxidation reactions: hydroxylation at C22, hydroxylation at C20, and cleavage of the C20-C22 bond [2, 8]. This enzyme is primarily expressed in the adrenal cortex, gonads, and placenta, but it is also found in the brain, skin, and immune cells [13, 18]. Mutations in the CYP11A1 gene can lead to lipoid congenital adrenal hyperplasia, a severe condition characterized by the inability to produce any steroid hormones [2, 16]. In the context of therapeutics, CYP11A1 is a target for treating hormone-dependent diseases such as castration-resistant prostate cancer (CRPC) and Cushing's syndrome [3, 9]. Inhibitors like ODM-208 (MK-5684) are designed to block the production of all downstream steroids, including androgens that fuel tumor growth [7, 9]. However, because CYP11A1 is essential for life-sustaining steroids like cortisol and aldosterone, pharmacological inhibition requires concomitant hormone replacement therapy to prevent adrenal insufficiency and electrolyte imbalances [9, 16]. Recent research also suggests its involvement in immune disorders like peanut allergy, where it regulates T-cell cytokine production [13, 17].

Other names

Cholesterol side-chain cleavage enzyme (P450scc)Cholesterol desmolaseCytochrome P450 family 11 subfamily A member 1CYP11ACYPXIA1Steroid 20-22-lyaseCholesterol monooxygenase (side-chain cleaving)

Inhibition of the enzymatic conversion of cholesterol to pregnenolone by binding to the active site or heme iron of the CYP11A1 enzyme, thereby blocking the rate-limiting step of steroidogenesis [3, 4, 7].