Cholic acid, a primary bile acid, is synthesized in the liver through the action of C27 dehydroxylase. It can be converted into two secondary bile acids, chenodeoxycholic acid and deoxycholic acid. The conjugation of bile acids occurs by combining cholic acid with either glycine or taurine. The structures of the major primary and secondary bile acids are shown in Figure 32.5. Primary bile acids are produced in the liver, while secondary bile acids are formed when intestinal bacteria act on primary bile acids. Conjugation of cholic acid with glycine or taurine is depicted at the bottom of the figure. 

In the liver, most bile acids are reabsorbed and recycled, with only a minor fraction (approximately 10% per day, or 200-400 mg) being lost in stool, as illustrated in Figure 32.7. However, lithocholic acid differs from other bile acids as it is preferentially sulfated in hepatocytes rather than conjugated with glycine or taurine. Most of the sulfate conjugates of lithocholic acid are eliminated from the body after each meal, as they are not substrates for the apical sodium-dependent bile acid transporter (ASBT). This prevents the accumulation of a potentially toxic molecule.

Bile acids also play a role in regulating whole-body cholesterol homeostasis. The cholesterol pool in the body reflects its daily synthesis as well as the small fraction obtained from dietary uptake, which is balanced against the loss of cholesterol from the body through bile, as depicted in Figure 32.8. Cholesterol can be excreted in its native form or after being converted into bile acids. Despite enterohepatic recycling, up to one-third of the cholesterol excreted per day is in the form of bile acids. Interrupting the enterohepatic circulation of bile acids is a strategy used to treat hypercholesterolemia, as it promotes increased conversion of cholesterol to bile acids, which are then eliminated from the body in feces.

Additionally, bile contains cholesterol and phosphatidylcholine. Cholesterol transport across the canalicular membrane involves the active transporters ABC G5 and ABC G8. These transporters, previously discussed in relation to the efflux of cholesterol from small intestinal epithelial cells, play a role in mediating cholesterol transport. Phosphatidylcholine, on the other hand, originates from the inner leaflet of the canalicular membrane and is transferred across the membrane by the multidrug resistance protein 3 (MDR3), which belongs to the ABC family of transporters.
Cholesterol Major bile acids Cholic acid HO Primary Secondary OH OH COOH C27 dehydroxylase 7˜-Hydroxylase (12˜-hydroxylase) HO HO OH COOH Chenodeoxycholic acid Deoxycholic acid Conjugation of bile acids HO OH COOH HO OH 3 7 12 OH C O O OH C O–H CH2N H Glycine, pKa˜3.7 Taurine, pKa˜1.5 or SO2O–HN CH2CH2 H HO OH COOH Ursodeoxycholic acid HO COOH Lithocholic acid Liver Colon (bacteria) •Fig. 32.5 Structuresofthemajorprimaryandsecondarybileacidsofbile.Primarybileacidsaresynthesizedintheliver.Secondarybileacidsareproducedwhenintestinalbacteriaactonprimarybileacids.Atthebottomofthefiguretheconjugationofcholicacidwithglycineortaurineisshown.
bile acids is produced, and daily synthesis is then equal only to the minor fraction (≈10%/day, or 200–400 mg) that escapes uptake and is lost in stool (
Fig. 32.7 ). The only exception to this rule is lithocholic acid, which is preferentially sulfated in the hepatocyte rather than being conjugated with glycine or taurine. The majority of the sulfate conjugates are lost from the body after each meal because they are not substrates for asbt, thereby avoiding accumulation of a potentially toxic molecule.
Some comment should also be made with respect to the role of bile acids in whole-body cholesterol homeostasis. The pool of cholesterol in the body reflects its daily synthesis as well as the relatively minor component derived from inefficient dietary uptake, balanced against loss from the body, which can only occur in health via bile (
Fig. 32.8 ). Cholesterol can be excreted in two forms, either as the native molecule or after its conversion to bile acids. The latter account for up to a third of the cholesterol excreted per day despite enterohepatic recycling. Thus one strategy for treating hypercholesterolemia is to interrupt the enterohepatic circulation of bile acids, which drives increased conversion of cholesterol to bile acids; the bile acids are then lost from the body in feces.
As noted earlier, bile also contains cholesterol and phosphatidylcholine. Cholesterol transport across the canalicular membrane is mediated at least in part by a heterodimer of the active transporters we discussed in as participating in the efflux of cholesterol from the small intestinal epithelial cells, namely, ABC G5 and ABC G8 (see 32.1 ). Phosphatidylcholine derives from the inner leaflet of the canalicular membrane and is specifically “flipped” across the membrane by another ABC family transporter called multidrug resistance protein 3 (MDR3). Furthermore, 5.0