Bile Acid Signaling in Liver Metabolism and Diseases
Enterohepatic circulation of the bile. Bile acids are synthesized from cholesterol in the hepatocytes. CYP7A1 regulates the rate-limiting step in the classic bile acid biosynthetic pathway. Bile acids are secreted into the gallbladder via BSEP. Phospholipids are transported via MDR2, and cholesterol is transported by the ABCG5/G8 transporters into the bile. In the gallbladder, bile acids, phospholipids, and cholesterol form mixed micelles to solubilize cholesterol and to reduce bile acid toxicity. After meal intake, gallbladder releases bile into the small intestine where bile acids facilitate the absorption of dietary lipids and vitamins. At the terminal ileum, most of the bile acids are reabsorbed by ASBT into the enterocytes, and secreted into the portal circulation via basolateral bile acid transporters Ostα/Ostβ. At the basolateral membrane of the hepatocytes, bile acids are taken up by the NTCP transporter for resecretion into the gallbladder.
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