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Journal of Lipid Research, Vol. 48, 2682-2692, December 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

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

Genta Kakiyama^*, Hideyuki Tamegai^*, Takashi Iida^1,*, Kuniko Mitamura, Shigeo Ikegawa, Takaaki Goto, Nariyasu Mano, Junichi Goto, Peter Holz^**, Lee R. Hagey and Alan F. Hofmann^1,

^* Department of Chemistry, College of Humanities and Sciences, Nihon University, Sakurajosui, Setagaya, Tokyo 156-8550, Japan
Faculty of Pharmaceutical Sciences, Kinki University, Kowakae, Higashi-Osaka 577-8502, Japan
Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama, Sendai 980-8578, Japan
^** Healesville Sanctuary, Healesville, Victoria 3777, Australia
Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0063

Published, JLR Papers in Press, September 4, 2007.

¹ To whom correspondence should be addressed. e-mail: takaiida{at}chs.nihon-u.ac.jp (T.I.); ahofmann{at}ucsd.edu (A.F.H.)

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 15-hydroxylithocholic acid (3,15-dihydroxy-5ß-cholan-24-oic acid). Taurine-conjugated CDCA constituted 78% of biliary bile acids, and (taurine-conjugated) 15-hydroxylithocholic acid constituted 11%. Proof of structure of the latter compound was obtained by its synthesis from CDCA via a ¹⁴ intermediate. The synthesis of its C-15 epimer, 15ß-hydroxylithocholic acid (3,15ß-dihydroxy-5ß-cholan-24-oic acid), is also reported. The taurine conjugate of 15-hydroxylithocholic acid was synthesized and shown to have chromatographic and spectroscopic properties identical to those of the compound isolated from bile. It is likely that 15-hydroxylithocholic acid is synthesized in the wombat hepatocyte by 15-hydroxylation of lithocholic acid that was formed by bacterial 7-dehydroxylation of CDCA in the distal intestine. Thus, the wombat appears to use 15-hydroxylation as a novel detoxification mechanism for lithocholic acid.

Supplementary key words bile acid synthesis • detoxification of bile acids • bile acid metabolism in marsupials • 15-hydroxylation • lithocholic acid

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