Isolation and chemical synthesis of a major, novel biliary bile acid in the common wombat (Vombatus ursinus): 15α-hydroxylithocholic acid

Genta Kakiyama, Hideyuki Tamegai, Takashi Iida, Kuniko Mitamura, Shigeo Ikegawa, Takaaki Goto, Nariyasu Mano, Junichi Goto, Peter Holz, Lee R. Hagey, Alan F. Hofmann

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

The major bile acids present in the gallbladder bile of the common Australian wombat (Vombatus ursinus) were isolated by preparative HPLC and identified by NMR as the taurine N-acylamidates of chenodeoxycholic acid (CDCA) and 15α-hydroxylithocholic acid (3α,15α-dihydroxy-5β- cholan-24-oic acid). Taurine-conjugated CDCA constituted 78% of biliary bile acids, and (taurine-conjugated) 15α-hydroxylithocholic acid constituted 11%. Proof of structure of the latter compound was obtained by its synthesis from CDCA via a Δ14 intermediate. The synthesis of its C-15 epimer, 15β-hydroxylithocholic acid (3α,15β-dihydroxy-5β- cholan-24-oic acid), is also reported. The taurine conjugate of 15α-hydroxylithocholic acid was synthesized and shown to have chromatographic and spectroscopic properties identical to those of the compound isolated frombile. It is likely that 15α-hydroxylithocholic acid is synthesized in the wombat hepatocyte by 15α-hydroxylation of lithocholic acid that was formed by bacterial 7α-dehydroxylation of CDCA in the distal intestine.jlr Thus, the wombat appears to use 15α- hydroxylation as a novel detoxification mechanism for lithocholic acid.

Original languageEnglish
Pages (from-to)2682-2692
Number of pages11
JournalJournal of lipid research
Volume48
Issue number12
DOIs
Publication statusPublished - 2007 Dec

Keywords

  • 15-hydroxylation
  • Bile acid metabolism in marsupials
  • Bile acid synthesis
  • Detoxification of bile acids
  • Lithocholic acid

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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