Bile is a watery mixture of organic and inorganic compounds. The most important organic components of bile are phosphatidylcholine (PC) or lecithin and conjugated bile salts. Bile can be released directly from the liver, where it is made, into the duodenum through the common bile duct, or it can be stored in the gallbladder until it is needed for digestion.

A. Structure
Bile acids have 24 carbons and contain two or three hydroxyl groups. They also have a side chain that ends in a carboxyl group. The carboxyl group has a pKa of approximately 6. In the duodenum, which has a pH of around 6, half of the bile acid molecules will be protonated and the other half will be deprotonated, forming bile salts. Although the terms bile acid and bile salt are often used interchangeably, both forms have α-oriented hydroxyl groups (below the plane of the rings) and β-oriented methyl groups (above the plane of the rings). This molecular structure gives bile acids and bile salts both a polar and nonpolar surface, allowing them to act as emulsifying agents in the intestine. They help prepare dietary fat (triacylglycerol [TAG]) and other complex lipids for degradation by pancreatic digestive enzymes.

B. Synthesis
Bile acids are synthesized in the liver through a multistep, multiorganelle pathway. This process involves inserting hydroxyl groups at specific positions on the steroid structure, reducing the double bond of the cholesterol B ring, and shortening the hydrocarbon chain by three carbons while introducing a carboxyl group at the end of the chain. The resulting compounds, cholic acid (a triol) and chenodeoxycholic acid (a diol), are known as primary bile acids. 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 cytochrome P450 monooxygenase associated with the endoplasmic reticulum. This enzyme is only found in the liver and its expression is downregulated by bile acids.

C. Conjugation
Before leaving the liver, bile acids are conjugated to either glycine or taurine (a byproduct of cysteine metabolism). This conjugation occurs through an amide bond between the carboxyl group of the bile acid and the amino group of the added compound. The resulting structures include glycocholic and glycochenodeoxycholic acids, as well as taurocholic and taurochenodeoxycholic acids. The ratio of glycine to taurine forms in bile is approximately 3 to 1. The addition of glycine or taurine leads to the presence of a carboxyl group with a lower pKa (due to glycine) or a sulfonate group (from taurine), both of which are fully ionized (negatively charged) in the alkaline pH of bile. The conjugated, ionized bile salts are more effective detergents than the unconjugated ones because of their enhanced amphipathic nature. As a result, only the conjugated forms are present in bile. Individuals with genetic deficiencies in the conversion of cholesterol to bile acids are treated with externally supplied chenodeoxycholic acid.

Bile salts are the primary means of cholesterol excretion, both as a metabolic product of cholesterol and as a solubilizer of cholesterol in bile.

D. Bacterial action on bile salts
Bile consists of a watery mixture of organic and inorganic compounds. Phosphatidylcholine (PC), or lecithin (see p. 202), and conjugated bile salts are quantitatively the most important organic components of bile. Bile can either pass directly from the liver, where it is synthesized, into the duodenum through the common bile duct, or be stored in the gallbladder when not immediately needed for digestion.
A. Structure
The bile acids contain 24 carbons, with two or three hydroxyl groups and a side chain that terminates in a carboxyl group. The carboxyl group has a pKa (see p. 6) of ~6. In the duodenum (pH ~6), this group will be protonated in half of the molecules (the bile acids) and deprotonated in the rest (the bile salts). The terms bile acid and bile salt are frequently used interchangeably, however. Both forms have hydroxyl groups that are α in orientation (they lie below the plane of the rings) and methyl groups that are β (they lie above the plane of the rings). Therefore, the molecules have both a polar and a nonpolar surface and can act as emulsifying agents in the intestine, helping prepare dietary fat (triacylglycerol [TAG]) and other complex lipids for degradation by pancreatic digestive enzymes.
B. Synthesis
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 18.8, 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. 18.9)].
C. Conjugation
Before the bile acids leave the liver, they are conjugated to a molecule of either glycine or taurine (an end product of cysteine metabolism) by an amide bond between the carboxyl group of the bile acid and the amino group of the added compound. These new structures include glycocholic and glycochenodeoxycholic acids and taurocholic and taurochenodeoxycholic acids (Fig. 18.10). The ratio of glycine to taurine forms in the bile is ~3/1. Addition of glycine or taurine results in the presence of a carboxyl group with a lower pKa (from glycine) or a sulfonate group (from taurine), both of which are fully ionized (negatively charged) at the alkaline pH of bile. The conjugated, ionized bile salts are more effective detergents than the unconjugated ones because of their enhanced amphipathic nature. Therefore, only the conjugated forms are found in the bile. Individuals with genetic deficiencies in the conversion of cholesterol to bile acids are treated with exogenously supplied chenodeoxycholic acid.
Bile salts provide the only significant mechanism for cholesterol excretion, both as a metabolic product of cholesterol and as a solubilizer of cholesterol in bile.
D. Bacterial action on bile salts