Submitted on July 27, 2007
Revised on September 4, 2007
Accepted on September 4, 2007
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, Kuniko Mitamura, Shigeo Ikegawa, Takaaki Goto, Nariyasu Mano, Junichi Goto, Peter Holz, Lee R. Hagey, and Alan F. Hofmann
Department of Medicine (Gastroenterology), University of California, San Diego, La Jolla, CA 92093-0063
Corresponding Author: ahofmann{at}ucsd.edu
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-acyl amidate of chenodeoxycholic acid and 15a-hydroxylithocholic acid (3a,15a-dihydroxy-5ß-cholan-24-oic acid). Taurine conjugated chenodeoxycholic acid constituted 78% of biliary bile acids, and 15a-hydroxylithocholic acid, 11%. Proof of structure of the latter compound was obtained by its synthesis from chenodeoxycholic acid via a 14¬¬¬ intermediate. The synthesis of its C-15 epimer, 15ß-hydroxylithocholic acid (3a,15ß-dihydroxy-5ß-cholan-24-oic acid) is also reported. The taurine conjugate of 15a-hydroxylithocholic acid was synthesized and shown to have chromatographic and spectroscopic properties identical to the compound isolated from bile. It is likely that 15a-hydroxylithocholic acid is synthesized in the wombat hepatocyte by 15a-hydroxylation of lithocholic acid that was formed by bacterial 7a-dehydroxylation of chenodeoxycholic acid in the distal intestine. Thus, the wombat appears to use 15a-hydroxylation as a novel detoxification mechanism for lithocholic acid.
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