Bile acids synthesis and enterohepatic circulation (WP4389)

Bile Acid Synthesis and Enterohepathic Circulation. In hepatocytes, cholesterol is acquired through de novo synthesis as well as receptor-mediated endocytosis of cholesterol-rich lipoproteins. Cholesterol is eliminated through bile acid synthesis and secretion. The first (and rate-limiting) step in cholesterol conversion to bile acids is catalyzed by CYP7A1. Bile acids are then secreted into the bile via ABCB11 and released into the small intestine. The majority of bile acids are re-absorbed into the enterocytes via ASBT and transported back to the liver via portal circulation via NTCP. In the hepatocyte, bile acids activate FXR, which inhibits CYP7A1. In the small intestine, bile acids also activate FXR to induce FGF15, which subsequently binds and activates FGFR4, leading to inhibition of CYP7A1, partially via ERK signaling. Based on figure 1 in [https://www.ncbi.nlm.nih.gov/pubmed/29653253 Wang et al].

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