Figure 2. Bile acid transport in the enterohepatic circulation.

In the enterohepatic circulation, bile acids are secreted from the canalicular side of hepatocytes into the bile and stored in the gallbladder. Meal intake stimulates gallbladder bile release into the small intestine, where ~95% of bile acids can be re-absorbed in the ileum and secreted into the portal circulation. Approximately 5% of the total bile acids are lost in feces. Bile acids are taken up by the hepatocytes from the basolateral side and re-secreted into the bile. Bile acid uptake and secretion are mediated by transporters. Bile salt export pump (BSEP) is the primary canalicular bile acid efflux transporter in hepatocytes. Cholesterol is secreted into the bile by the ATP binding cassette (ABC)G5/ABCG8 heterodimer, and phospholipids are secreted by ABCB4 into the bile. Cholesterol, bile acids and phospholipids are the major constituents in the bile. They form mixed micelles for cholesterol solubilization and to prevent bile acid damage to the biliary system. In the small intestine, bile acids are taken up into the enterocytes by apical sodium-dependent bile salt transporter (ASBT) and are secreted into the portal circulation by the organic solute transporter (OST)α/OSTβ heterodimer. Sodium–dependent taurocholate transporter(NTCP) is the major basolateral conjugated bile acid uptake transporter on hepatocytes, while OATP isoforms can also mediate uptake of primarily unconjugated bile acids.