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标题：Isolation and chemical synthesis of a major, novel biliary bile acid in the common wombat (Vombatus ursinus): 15{alpha}-hydroxylithocholic acid
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作者：Kakiyama, Genta ; Tamegai, Hideyuki ; Iida, Takashi 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2007
卷号：48
期号：12
页码：2682-2692
DOI：10.1194/jlr.M700340-JLR200
出版社：American Society for Biochemistry and Molecular Biology
摘要：The major bile acids present in the gallbladder bile of thecommon Australian wombat (Vombatus ursinus) were isolated bypreparative HPLC and identified by NMR as the taurine N-acylamidatesof chenodeoxycholic acid (CDCA) and 15 ${alpha}$ -hydroxylithocholic acid(3 ${alpha}$ ,15 ${alpha}$ -dihydroxy-5ß-cholan-24-oic acid). Taurine-conjugatedCDCA constituted 78% of biliary bile acids, and (taurine-conjugated)15 ${alpha}$ -hydroxylithocholic acid constituted 11%. Proof of structureof the latter compound was obtained by its synthesis from CDCAvia a ${Delta}$ ¹⁴ intermediate. The synthesis of its C-15 epimer, 15ß-hydroxylithocholicacid (3 ${alpha}$ ,15ß-dihydroxy-5ß-cholan-24-oic acid),is also reported. The taurine conjugate of 15 ${alpha}$ -hydroxylithocholicacid was synthesized and shown to have chromatographic and spectroscopicproperties identical to those of the compound isolated frombile. It is likely that 15 ${alpha}$ -hydroxylithocholic acid is synthesizedin the wombat hepatocyte by 15 ${alpha}$ -hydroxylation of lithocholicacid that was formed by bacterial 7 ${alpha}$ -dehydroxylation of CDCAin the distal intestine. Thus, the wombat appears to use 15 ${alpha}$ -hydroxylationas 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