Bile acid biosynthetic pathway

The bile acid biosynthetic pathway is the primary metabolic route for the conversion of cholesterol into bile acids, occurring predominantly in hepatocytes (Chiang, J. Y. L., 2009, Journal of Lipid Research). This pathway is critical for maintaining cholesterol homeostasis and facilitating the intestinal absorption of dietary lipids and fat-soluble vitamins (StatPearls, "Physiology, Bile", 2023). The "classic" pathway is initiated by the rate-limiting enzyme cholesterol 7 alpha-hydroxylase (CYP7A1), while an "alternative" pathway begins with sterol 27-hydroxylase (CYP27A1) (PubMed, PMID: 19047577). Regulation is achieved through a complex feedback loop where bile acids activate the farnesoid X receptor (FXR), leading to the induction of FGF19 (in humans) which subsequently suppresses CYP7A1 expression (Cell Metabolism, 2005). Dysregulation of these pathways contributes to cholestatic liver diseases, gallstone formation, and metabolic disorders like NASH (Physiological Reviews, 2003). Therapeutic strategies include FXR agonists like obeticholic acid to reduce bile acid synthesis and IBAT inhibitors like odevixibat to interrupt the enterohepatic circulation (Nature Reviews Gastroenterology & Hepatology, 2020).

Other names

Bile acid synthesisPrimary bile acid biosynthesisCholesterol 7-alpha-hydroxylase pathway

Drugs modulate this pathway by activating nuclear receptors (e.g., FXR) to suppress synthesis, inhibiting bile acid transporters (e.g., IBAT/ASBT) to prevent reabsorption, or sequestering bile acids in the gut to promote excretion.