Synthesis of the 3-sulfates of S-acyl glutathione conjugated bile acids and their biotransformation by a rat liver cytosolic fraction

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• 作者：Kuniko Mitamura^a ; Naohiro Hori^a ; Shiori Mino^a ; Takashi Iida^b ; Alan F. Hofmann^c ; Shigeo Ikegawa^a ; ^{ikegawa@phar.kindai.ac.jp}
• 关键词：BAs ; bile acids ; CoA ; coenzyme A ; GSH ; glutathione ; NAC ; N-acetylcysteine ; LC ; liquid chromatography ; ESI ; electrospray ionization ; MS ; mass spectrometry ; CA-GSH ; S-(cholyl)glutathione ; CDCA-GSH ; S-(chenodeoxycholyl) glutathione ; DCA-GSH ; S-(deoxycholyl)
• 刊名：Chemistry and Physics of Lipids
• 出版年：2012
• 期刊代码：44_00093084
• 类别：bio
• 出版时间：April, 2012
• 卷：165
• 期：3
• 页码：261-269
• 文件大小：600 K

摘要

The 3-sulfates of the S-acyl glutathione (GSH) conjugates of five natural bile acids (cholic, chenodeoxycholic, deoxycholic, ursodeoxycholic, and lithocholic) were synthesized as reference standards in order to investigate their possible formation by a rat liver cytosolic fraction. Their structures were confirmed by proton nuclear magnetic resonance, as well as by means of electrospray ionization-linear ion-trap mass spectrometry with negative-ion detection. Upon collision-induced dissociation, structurally informative product ions were observed. Using a triple-stage quadrupole instrument, selected reaction monitoring analyses by monitoring characteristic transition ions allowed the achievement of a highly sensitive and specific assay. This method was used to determine whether the 3-sulfates of the bile acid-GSH conjugates (BA-GSH) were formed when BA-GSH were incubated with a rat liver cytosolic fraction to which 3鈥?phosphoadenosine 5鈥?phosphosulfate had been added. The S-acyl linkage was rapidly hydrolyzed to form the unconjugated bile acid. A little sulfation of the GSH conjugates occurred, but greater sulfation at C-3 of the liberated bile acid occurred. Sulfation was proportional to the hydrophobicity of the unconjugated bile acid. Thus GSH conjugates of bile acids as well as their C-3 sulfates if formed in vivo are rapidly hydrolyzed by cytosolic enzymes.