Cytochrome P450 family 8 subfamily B member 1 (CYP8B1)

Cytochrome P450 family 8 subfamily B member 1 (CYP8B1) is a membrane-bound monooxygenase enzyme of the cytochrome P450 superfamily. It catalyzes the 12α-hydroxylation of 7α-hydroxy-4-cholesten-3-one—an essential step in the biosynthesis of cholic acid, one of two primary human bile acids. The ratio of cholic acid to chenodeoxycholic acid synthesized helps regulate cholesterol and lipid absorption in the intestine. CYP8B1 has a unique intronless human gene. Its modulation is implicated in several metabolic disorders—and therapeutic targeting is being explored for conditions such as nonalcoholic fatty liver disease, obesity, type 2 diabetes, and cardiovascular disease. Currently, nonselective azole antifungals can inhibit CYP8B1, though selective inhibitors are still needed for clinical use.

Other names

Sterol 12-alpha-hydroxylaseCytochrome P450 8B1CYP12CYPVIII B17-alpha-hydroxy-4-cholesten-3-one 12-alpha-hydroxylaseCP8BCYPVIIIB1Cytochrome P450, family 8, subfamily B, polypeptide 1

Inhibition of CYP8B1 blocks 12α-hydroxylation of 7α-hydroxy-4-cholesten-3-one, reducing cholic acid synthesis. This alters bile acid composition, affects cholesterol and lipid absorption, and can decrease hepatic fat accumulation. Binding to the heme iron of the CYP8B1 active site (by azole inhibitors). No highly selective inhibitors are currently described.