Synthesis of Bile acids

Bile acids are synthesized in the liver by a multistep, multiorganelle pathway in which hydroxyl groups are inserted at specific positions on the steroid structure; the double bond of the cholesterol B ring is reduced; and the hydrocarbon chain is shortened by three carbons, introducing a carboxyl group at the end of the chain.

The most common resulting compounds, cholic acid (a triol) and chenodeoxycholic acid (a diol), as shown in Figure 1, are called primary bile acids. [Note: The rate-limiting step in bile acid synthesis is the introduction of a hydroxyl group at carbon 7 of the steroid nucleus by 7-α-hydroxylase, a SER-associated cytochrome P450 monooxygenase found only in liver. Expression of the enzyme is downregulated by bile acids (Fig. 2)].

Figure 1: Bile acids. [Note: The ionized forms are bile salts.]

Figure 2 : Synthesis of the bile acids cholic acid and chenodeoxycholic acid from cholesterol.