PMID: 8608157Mar 29, 1996Paper

Formation of cholic acid and chenodeoxycholic acid from 7 alpha-hydroxycholesterol and 27-hydroxycholesterol by primary cultures of human hepatocytes

Biochimica Et Biophysica Acta
G SauterG Paumgartner

Abstract

It has been suggested that chenodeoxycholic acid is preferentially formed by the alternative or 'acidic' pathway of bile acid biosynthesis starting with 27-hydroxylation of cholesterol, while cholic acid is derived from 7 alpha-hydroxycholesterol which initiates the 'neutral' pathway. We have studied bile acid formation from each of these precursors using human hepatocytes cultured in a novel sandwich collagen configuration. Culture supernatants were analyzed using capillary gas chromatography and gas chromatography-mass spectrometry. 27-Hydroxycholesterol and 7 alpha-hydroxycholesterol were both found to be efficiently converted to cholic acid as well as chenodeoxycholic acid. Analysis of acidic intermediates after addition of 7 alpha-hydroxycholesterol to the cultures revealed a significant increase of side-chain oxygenated C24- and C27-steroids with a 3-oxo-7 alpha-hydroxy-delta 4-ring structure. These data indicate that (i) the 'neutral' pathway is connected to the 'acidic' pathway by side-chain oxidation of C27-steroids with a 3-oxo-7 alpha-hydroxy-delta 4-ring structure and that (ii) the relative formation of cholic acid and chenodeoxycholic acid is regulated by metabolic events distal to the initial hydroxylation at eith...Continue Reading

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Citations

Apr 1, 1999·Toxicology in Vitro : an International Journal Published in Association with BIBRA·H HildebrandA Bader
Dec 9, 2000·Biochimica Et Biophysica Acta·N B Javitt
Feb 22, 2012·Toxicology and Applied Pharmacology·Tracy L MarionKim L R Brouwer
May 29, 2000·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·M AxelsonC Einarsson
Sep 1, 2018·European Journal of Drug Metabolism and Pharmacokinetics·Olivier FardelYannick Parmentier
Jan 5, 2000·Physiological Reviews·G J Schroepfer

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