Influence of uridine diphosphoglucuronic acid on bilirubin glucuronidation in liver microsomes from normal and spironolactone-treated rats.
The formation of bilirubin glucuronides was studied using liver microsomes from normal and spironolactone (SP)-treated rats. Increasing amounts of uridine diphosphoglucuronic acid (UDPGA) were added to the incubation mixture to investigate the influence of this nucleotide on bilirubin glucuronidation. The results demonstrated that microsomal preparations from SP-treated rats had a greater capability for bilirubin glucuronidation than normal microsomes which was mostly produced at the expense of bilirubin diglucuronide (BDG) formation. On the other hand, the increase in UDPGA concentration in the incubation mixture also produced an increase of BDG formation which was more important than that of monoglucuronide. These results support the hypothesis of different subunits in the glucuronyl-transferase moiety with different substrate specificities. In addition, the inducer effect of SP on bilirubin glucuronidation is in agreement to the results obtained in living rats which were described previously.
Mottino
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AD
Instituto de Fisiología Experimental, CONICET - Universidad Nacional de Rosario, Argentina.
Rodríguez Garay
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EA
D000818:Animals; D001663:Bilirubin / Q000031:analogs & derivatives* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D014453:Glucuronosyltransferase / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains; D013148:Spironolactone / Q000494:pharmacology*; D014535:Uridine Diphosphate Glucuronic Acid / Q000378:metabolism*; D014539:Uridine Diphosphate Sugars / Q000378:metabolism*
D014539:Uridine Diphosphate Sugars; D014535:Uridine Diphosphate Glucuronic Acid; C016266:bilirubin glucuronate; D013148:Spironolactone; D014453:Glucuronosyltransferase; D001663:Bilirubin