Cholesterol 7-alpha-monooxygenase (Cytochrome P450 7A1) (CYP7A1)

Cholesterol 7-alpha-monooxygenase (CYP7A1) is a hepatic cytochrome P450 heme enzyme located in the endoplasmic reticulum that catalyzes the 7α-hydroxylation of cholesterol, producing 7α‑hydroxycholesterol, the first and rate-limiting step in the classic pathway of bile acid synthesis, thereby playing a central role in cholesterol catabolism and bile acid homeostasis. It is encoded by the human CYP7A1 gene on chromosome 8 and is regulated transcriptionally by bile acid–activated farnesoid X receptor (FXR) via SHP and LRH‑1, as well as by inflammatory cytokines; kinetic studies indicate high catalytic efficiency with the first electron transfer step becoming rate-limiting in the overall reaction cycle.

Other names

Cholesterol 7 alpha-hydroxylaseCholesterol 7α-hydroxylaseCytochrome P450 7A124-hydroxycholesterol 7-alpha-hydroxylaseCYP7A1

Enzyme inhibition of CYP7A1 would reduce bile acid biosynthesis by blocking conversion of cholesterol to 7α-hydroxycholesterol (the rate-limiting step). Enzyme activation/induction of CYP7A1 would increase bile acid synthesis and cholesterol catabolism. FXR agonists repress CYP7A1 transcription via SHP induction and LRH-1 interference (indirect downregulation).