کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1177120 | 961947 | 2009 | 7 صفحه PDF | دانلود رایگان |

Acyl-adenylates and acyl-CoA thioesters of bile acids (BAs) are reactive acyl-linked metabolites that have been shown to undergo transacylation-type reactions with the thiol group of glutathione (GSH), leading to the formation of thioester-linked GSH conjugates. In the current study, we examined the transformation of cholyl-adenylate (CA–AMP) and cholyl-coenzyme A thioester (CA–CoA) into a cholyl-S-acyl GSH (CA–GSH) conjugate by rat hepatic glutathione S-transferase (GST). The reaction product was analyzed by liquid chromatography (LC)/electrospray ionization (ESI)–linear ion trap mass spectrometry (MS). The GST-catalyzed formation of CA–GSH occurred with both CA–AMP and CA–CoA. Ursodeoxycholic acid, lithocholic acid, and 2,2,4,4-2H4-labeled lithocholic acid were administered orally to biliary fistula rats, and their corresponding GSH conjugates were identified in bile by LC/ESI–MS2. These in vitro and in vivo studies confirm a new mode of BA conjugation in which BAs are transformed into their GSH conjugates via their acyl-linked intermediary metabolites by the catalytic action of GST in the liver, and the GSH conjugates are then excreted into the bile.
Journal: Analytical Biochemistry - Volume 384, Issue 2, 15 January 2009, Pages 224–230