Sterol 12-alpha-hydroxylase (CYP8B1)

Sterol 12-alpha-hydroxylase (CYP8B1) is a key cytochrome P450 enzyme in the liver that determines the composition of the primary bile acid pool by catalyzing the 12α-hydroxylation of 7α-hydroxy-4-cholesten-3-one to produce cholic acid [1, 3, 10]. By regulating the ratio of cholic acid to chenodeoxycholic acid, the enzyme significantly influences the hydrophobicity of bile and the efficiency of intestinal absorption of dietary lipids and cholesterol [1, 5, 20]. CYP8B1 expression is often elevated in states of obesity and type 2 diabetes, and its product, cholic acid, has been linked to impaired insulin signaling and increased hepatic lipogenesis [1, 11, 14]. Inhibition of CYP8B1 is a recognized therapeutic strategy for treating nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome, as it shifts the bile acid pool toward chenodeoxycholic acid derivatives that activate the farnesoid X receptor (FXR) and improve metabolic homeostasis [6, 7, 19]. Although selective clinical candidates are still in development, several non-selective imidazole antifungals, such as miconazole and tioconazole, have been identified as potent inhibitors of the enzyme [1, 9].

Other names

Cytochrome P450 8B17-alpha-hydroxycholest-4-en-3-one 12-alpha-hydroxylase7-alpha-hydroxy-4-cholesten-3-one 12-alpha-hydroxylaseCYP12CP8BSteroid 12-alpha-hydroxylase

Inhibition of 12-alpha-hydroxylase activity to decrease cholic acid synthesis and increase chenodeoxycholic acid levels, leading to enhanced FXR/TGR5 signaling and reduced dietary fat absorption.