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Primary Bile Acids / Primary Bile Salts (PBAs) are synthesized in hepatocytes by two pathways: the classic pathway initiated by Cholesterol 7 alpha-hydroxylase (CYP7A1) and the alternative, neutral pathway initiated by 24-hydroxycholesterol-7 alfa hydroxylase (CYP27A1/CYP7B1)
Cholic Acid (CA) and Chenodeoxycholic Acid (CDCA) are the most prevalent Primary Bile Acids / Primary Bile Salts (PBAs) in humans. In humans Primary Bile Acids / Primary Bile Salts (PBAs) undergo both glycine and taurine conjugation, with a preference for glycine conjugation. After conjugation, Primary Bile Acids / Primary Bile Salts (PBAs) are transported out of the liver via Bile Salts/Bile acids Export Pump (BSEP) to the gallbladder and then to the small intestine. Epimerization and the Cyp2c70 way take place in mice
Although, in the classic pathway, the enzymes Cholesterol 7 alpha-hydroxylase (CYP7A1) and CYP7B1 are both involved, for the neutral pathway only CYP7B1 is relevant.
Fuchs & Trauner 2022 Nat Rev Gastroenterol Hepatol doi: 10.1038/s41575-021-00566-7
The liver could effectively synthesize Primary bile acids (PBAs) 7 days after birth, and fecal primary bile acids tend to be stable after the neonate stage.
FGF-15 is produced in enterocytes in response to bile acids' interaction with the FXR and is secreted into the portal vein. In the liver, FGF15 activates the FGFR4 /beta-Klotho receptor on hepatocytes. The resulting activation of ERK/JNK leads to the inhibition of CYP7A1 /CYP8B1 and the inhibition of the classic biosynthesis of bile acids from cholesterol . The alternative synthesis route with the enzymes CYP27A1/CYP7B1 , which initially leads to oxysterols , is not affected. The inhibition of bile acids' classic biosynthesis can also be achieved after activating the TLR /MyD88 complex by inhibiting ERK/JNK. The N-acylphosphatidylethanolamine-selective phospholipase D (NAPE-PLD) is activated by bile acids, which induces the formation of anti-inflammatory and antibacterial N-acetylethanolamines (NAEs) , reciprocally regulates bile acid synthesis
Fecal losses of bile acids are balanced by de novo synthesis in the liver, thus ensuring a stable pool size
see also:
Conjugated bile acids