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 7α-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 7α-hydroxycholesterol were both found to be efficiently converted to cholic acid as well as chenodeoxycholic acid. Analysis of acidic intermediates after addition of 7α-hydroxycholesterol to the cultures revealed a significant increase of side-chain oxygenated C 24- and C 27-steroids with a 3-oxo-7α-hydroxy-Δ4-ring structure. These data indicate that (i) the ‘neutral’ pathway is connected to the ‘acidic’ pathway by side-chain oxidation of C 27-steroids with a 3-oxo-7α-hydroxy-Δ4-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 either position 7 or position 27 of the cholesterol molecule.

Full Text
Paper version not known

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call