Bile acid transport in the enterohepatic circulation. (IMAGE)
Caption
In hepatocytes, bile acids are secreted into bile canaliculi by bile salt export pump (BSEP), cholesterol is secreted by ATP binding cassette subfamily G member 5 (ABCG5) and ABCG8 heterodimer and phospholipids are secreted by multidrug resistance-3 (human MDR3, mouse MDR2). In bile, cholesterol, bile acids and phospholipids form mixed micelles. Bile acids are secreted into small intestine lumen, where bile acids facilitate dietary lipid absorption. Bile acids are absorbed in the terminal ileum by apical sodium-dependent bile acid transporter (ASBT). In enterocytes, bile acids bind intestinal bile acid binding protein (I-BABP). At the basolateral side of enterocytes, bile acid efflux is mediated by organic solute transporter α (OSTα) and OSTβ heterodimers. Bile acids are transported in portal blood to the liver where bile acids are taken up by hepatocytes via the Na+-dependent taurocholate co-transporting polypeptide (NTCP) and organic anion transporting polypeptide (OATP) isoforms. A small amount of bile acids that are not taken up by hepatocytes enter the systemic circulation. Hepatocytes also efflux bile acids across the basolateral membrane via multidrug resistance-associated protein 3 (MRP3) and MRP4. This process is often increased during cholestasis as an adaptive protection against hepatic bile acid accumulation, resulting in significantly increased bile acid concentration in systemic circulation.
Credit
By Tiangang Li, Mohammad Nazmul Hasan, Lijie Gu.
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License
CC BY-NC