cholesterol desmolase
Summary
Cholesterol desmolase (side-chain cleavage enzyme, P450scc, encoded by CYP11A1) converts cholesterol to pregnenolone on the inner mitochondrial membrane. It catalyses the rate-limiting and committed step of all steroid hormone synthesis and is stimulated by ACTH and by angiotensin II.
Detail
Cholesterol reaches the enzyme via StAR protein, which transports it across the mitochondrial membrane and is itself the true rate-limiting step of acute steroidogenesis. Cholesterol desmolase then cleaves the side chain to yield pregnenolone, the precursor of mineralocorticoids, glucocorticoids, and sex steroids alike. Because it sits above every branch of the pathway, complete deficiency (congenital lipoid adrenal hyperplasia) abolishes all adrenal and gonadal steroid output: patients present with salt wasting, hyperkalaemia, hypotension, and 46,XY genetic males are phenotypically female externally. Cholesterol accumulates in the adrenal cortex, producing the lipoid appearance that gives the disorder its name. Ketoconazole inhibits desmolase along with other P450 steroidogenic enzymes, which is why it can be used to lower cortisol in Cushing syndrome.
Sources
- First Aid for the USMLE Step 1
- Lippincott Illustrated Reviews: Biochemistry
Reviewed by AnkiBoss editorial — medical student review. Information here is for study reference only and is not medical advice. Spotted an error? Let us know.