CholesterolDesmolase

Cholesterol desmolase, also known as cholesterol 20,22‑desmolase or CYP11A1, is a mitochondrial cytochrome P450 enzyme that catalyzes the first and rate‑limiting step in the biosynthesis of steroid hormones. The enzyme converts cholesterol to pregnenolone through a three‑step oxidative cleavage of the side‑chain between carbon atoms 20 and 22, producing isocaproic aldehyde and isocaproic acid as by‑products. This reaction requires electrons supplied by NADPH via adrenodoxin reductase and adrenodoxin, and it depends on the presence of heme as a prosthetic group.

In mammals, cholesterol desmolase is expressed primarily in the adrenal cortex, gonads, and placenta, where it initiates the production of glucocorticoids, mineralocorticoids, and sex steroids. Its activity is regulated by trophic hormones such as ACTH, LH, and hCG, which increase transcription of the CYP11A1 gene and promote mitochondrial import of the enzyme. Genetic defects in the CYP11A1 gene can lead to congenital adrenal hyperplasia, characterized by reduced steroid output and accumulation of cholesterol precursors.

The enzyme is a target for pharmacological modulation in disorders of steroid excess, and inhibitors have been investigated for treatment of Cushing’s syndrome and hormone‑dependent cancers. Conversely, enhancing cholesterol desmolase activity has been explored as a strategy to boost steroidogenesis in certain infertility treatments. Research continues to delineate the enzyme’s structure‑function relationships, its interaction with mitochondrial membrane proteins, and its role in cholesterol homeostasis beyond steroid synthesis.