Regulation of Bile Acid and Cholesterol Metabolism by PPARs

Figure 1

Bile acid synthesis. Bile acids are synthesized from cholesterol in the liver through two pathways: the classic pathway and the alternative pathway. In human liver, bile acid synthesis mainly produces two primary bile acids, cholic acid (CA), and chenodeoxycholic acid (CDCA). Key regulatory enzymes in both pathways are indicated. CYP7A1 catalyzes the first the rate-limiting step in the classic pathway to convert cholesterol into 7𝛼-hydroxycholesterol, while CYP27A1 initiates the alternative pathway by converting cholesterol into 27-hydroxycholesterol, which is then 7𝛼-hydroxylated by oxysterol 7𝛼-hydroxylase (CYP7B1). CYP8B1 regulates the cholic acid synthesis in the classic pathway. In the intestine, primary bile acid CA and CDCA are dehydroxylated at the 7𝛼-position by the bacterial enzymes to produce the secondary bile acids, deoxycholic acid (DCA), and lithocholic acid (LCA), respectively.