Hepatocytes, glucuronide formation

Ki etz-Rommel, A. Boelsterli, U.A. "Diclofenac Covalent Protein Binding is Dependent on Acyl Glucuronide Formation and is Inversely Related to P450-mediated Acute Cell Injury in Cultured Rat Hepatocytes," Toxicol. Appl. Pharmacol. 120(1), 155-161 (1993). 

Koster, A. S., Frankhuijzen-Sierevogel, A. C., and Mentrup, A. (1986). Stereoselective Formation of FenoteroI-para-GIucuronide and Fenoterol-raeta-Glucuronide in Rat Hepatocytes and Enterocytes, Biochem. Pharmacol., 35 1981-1985. 

Formation of bilirubin diglucuronide. Glucuronidation occurs in two steps via formation of monoglucuronide. Mono-and diglucuronides are more water-soluble and less lipophilic than bilirubin. Conversion of bilirubin to water-soluble products is obligatory for excretion of bilirubin from hepatocytes. M, Methyl V, vinyl UPD-GA, UDP-glucuronic acid. 

The glucuronide metabolite of AZT was isolated from rat and human liver microsomal incubations (177), and the formation of a toxic metabolite of AZT was demonstrated in rat hepatocytes and liver microsomes (177). The metabolism of tamoxifen was examined in human liver homogenate and human Hep G2 cell line preparations by LC/API/MS (178). Several metabolites were detected in the human liver homogenate extracts, namely, N-didesmethyltamoxifen, a-hydroxy-tamoxifen, 4-hydroxytamoxifen, N-desmethyltamoxifen, and tamoxifen N-oxide. All of these metabolites, except the N-didesmethyltamoxifen, were observed in the samples after incubating tamoxifen with the human Hep G2 cell line. In-vitro studies have also used MS to examine potential drug-drug interactions. For example, (179) demonstrated that the a2-agonist, dexmedetomidine, inhibited metabolism of the anesthetic alfentanil, whereas clonidine had no effect. 

Froehlich AK, Girreser D, Clement B. Metabolism of A-hydroxyguanidines (A-hydroxydebrisoquine) in human and porcine hepatocytes reduction and formation of glucuronides. Drug Metabo Dispos 2005 33 1532-1537. 

Koster, A.S. Frankhuijzen-Sierevogel, A.C. Mentrup, A. Stereoselective formation of fenoterol-para-glucuronide and fenoterol-meta-glucuronide in rat hepatocytes and enterocytes. Biochem. Pharmacol. 1986, 35, 1981-1985. 

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