Glucuronidation of 3'-azido-3'-deoxythymidine by rat and human liver microsomes.
The glucuronidation of 3'-azido-3'-deoxythymidine (AZT) by rat and human liver microsomes has been studied in vitro. The AZT-glucuronide was preliminarily identified through specific hydrolysis by beta-glucuronidase and rigorous product identification was performed by high-field proton nuclear magnetic resonance and fast-atom-bombardment mass spectrometry. A beta-linked 5'-O-glucuronide was the exclusive product formed in liver microsomes. Rat and human liver microsomal uridine 5'-diphosphoglucuronyltransferase activities toward AZT were investigated. These studies revealed that AZT had a lower Km and a 5-6-fold higher relative catalytic efficiency for uridine 5'-diphosphoglucuronyltransferase in human as compared to rat liver microsomes which may play a role in the quantitative differences observed in the degree of AZT glucuronidation between rat and human.
Cretton
E M
EM
Department of Pharmacology, University of Alabama, Birmingham 35294.
Waterhous
D V
DV
Bevan
R
R
Sommadossi
J P
JP
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005965:Glucuronates / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D015215:Zidovudine / Q000378:metabolism*
D005965:Glucuronates; D015215:Zidovudine; D014453:Glucuronosyltransferase