Abstract
Bile acids entering into enterohepatic circulating are primary acids synthesized from cholesterol in hepatocyte. They are secreted actively across canalicular membrane and carried in bile to gallbladder, where they are concentrated during digestion. About 95 % BAs are actively taken up from the lumen of terminal ileum efficiently, leaving only approximately 5 % (or approximately 0.5 g/d) in colon, and a fraction of bile acids are passively reabsorbed after a series of modifications in the human large intestine including deconjugation and oxidation of hydroxy groups. Bile salts hydrolysis and hydroxy group dehydrogenation reactions are performed by a broad spectrum of intestinal anaerobic bacteria. Next, hepatocyte reabsorbs bile acids from sinusoidal blood, which are carried to liver through portal vein via a series of transporters. Bile acids (BAs) transporters are critical for maintenance of the enterohepatic BAs circulation, where BAs exert their multiple physiological functions including stimulation of bile flow, intestinal absorption of lipophilic nutrients, solubilization, and excretion of cholesterol. Tight regulation of BA transporters via nuclear receptors (NRs) is necessary to maintain proper BA homeostasis. In conclusion, disturbances of enterohepatic circulation may account for pathogenesis of gallstones diseases, including BAs transporters and their regulatory NRs and the metabolism of intestinal bacterias, etc.
Highlights
Gallstone disease is a frequent and economically relevant health problem worldwide
Bile acids are synthesized from cholesterol by either a classical pathway or an alternative pathway resulting in formation of CA or chenodeoxycholic acid (CDCA)
In addition to cytochrome P450 7A1 (Cyp7a1) and Cyp8b1, Farnesoid X receptor (FXR) regulates genes involved in bile acid (e.g., BSEP, MRP2) and phospholipid secretion across the bile canalicular membrane, bile acid transport (ASBT, NTCP, IBABP, OSTa–OSTb), and bile acid conjugation and detoxification (e.g., SULT2A1, UGT2B4, BACS, BAT) (Lee et al 2006).These findings suggest that FXR is the primary bile acid sensor that coordinately regulates bile acid metabolism
Summary
Small heterodimer partner Tumor necrosis factor alpha Hepatic nuclear factor 1a Ileal lipid binding protein Sulfotransferases2A1 Uridine dipho-sphate glucuronosyltransferase 2 family, polypeptide B4 Bile acid-CoA synthetase Bile acid-CoA amino acid N-acetyltransferase Cholecystokinin Fibroblast growth factor Niemann-Pick C1-like L1
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