Bioconversion of 3β-hydroxy-5-cholenoic acid into chenodeoxycholic acid by rat brain enzyme systems

Nariyasu Mano, Yoshiaki Sato, Masanori Nagata, Takaaki Goto, Junichi Goto

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

We have previously demonstrated that the rat brain contains three unconjugated bile acids, and chenodeoxycholic acid (CDCA) is the most abundantly present in a tight protein binding form. The ratio of CDCA to the other acids in rat brain tissue was significantly higher than the ratio in the peripheral blood, indicating a contribution from either a specific uptake mechanism or a biosynthetic pathway for CDCA in rat brain. In this study, we have demonstrated the existence of an enzymatic activity that converts 3β-hydroxy-5-cholenoic acid into CDCA in rat brain tissue. To distinguish marked compounds from endogenous related compounds, 18O-labeled 3β-hydroxy-5-cholenoic acid, 3β,7α-dihydroxy-5-cholenoic acid, and 7α-hydroxy-3-oxo- 4-cholenoic acid were synthesized as substrates for in vitro incubation studies. The results clearly suggest that 3β-hydroxy-5-cholenoic acid was converted to 3β,7α-dihydroxy-5-cholenoic acid by microsomal enzymes. The 7α-hydroxy-3-oxo-4-cholenoic acid was produced from 3β,7α- dihydroxy-5-cholenoic acid by the action of microsomal enzymes, and δ4-3-oxo acid was converted to CDCA by cytosolic enzymes. These findings indicate the presence of an enzymatic activity that converts 3β-hydroxy-5-cholenoic acid into CDCA in rat brain tissue. Furthermore, this synthetic pathway for CDCA may relate to the function of 24S-hydroxycholesterol, which plays an important role in cholesterol homeostasis in the body.

Original languageEnglish
Pages (from-to)1741-1748
Number of pages8
JournalJournal of lipid research
Volume45
Issue number9
DOIs
Publication statusPublished - 2004 Sep

Keywords

  • Biosynthesis
  • Brain bile acid
  • Cholesterol homeostasis
  • Stable isotope dilution

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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