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Glucuronidation of Retinoids by Rat Recombinant UDP: Glucuronosyltransferase 1.1 (Bilirubin UGT)

Abstract Rat liver recombinant BR 1 UGT1.1 was found to have significant activity toward retinoid substrates. UGT1.1 glucuronidation activity was 91 ± 18 pmol/mg × min for atRA and 113 ± 19 pmol/mg × min for 5,6-epoxy-atRA. The apparent K M and V max of atRA acid glucuronidation by UGT1.1 were 59.1 ± 5.4 μM and 158 ± 43 pmol/mg × min, respectively. SDS-PAGE and Western blot analysis of UGT1.1-transfected HK293 membrane proteins photolabeled with 11,12- 3 HatRA revealed a protein of ∼56 kDa that was labeled by 3 HatRA, detected by anti-pNP UGT antibody and not present in membranes from nontransfected HK293 cells. Liver microsomes from Gunn rats, which lack UGT1.1, had significant activity toward atRA (111 ± 28 pmol/mg × min). http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Drug Metabolism and Disposition Am. Soc for Pharma & Experimental Therapeutics

Glucuronidation of Retinoids by Rat Recombinant UDP: Glucuronosyltransferase 1.1 (Bilirubin UGT)

Abstract

Abstract Rat liver recombinant BR 1 UGT1.1 was found to have significant activity toward retinoid substrates. UGT1.1 glucuronidation activity was 91 ± 18 pmol/mg × min for atRA and 113 ± 19 pmol/mg × min for 5,6-epoxy-atRA. The apparent K M and V max of atRA acid glucuronidation by UGT1.1 were 59.1 ± 5.4 μM and 158 ± 43 pmol/mg × min, respectively. SDS-PAGE and Western blot analysis of UGT1.1-transfected HK293 membrane proteins photolabeled with 11,12- 3 HatRA revealed a protein of ∼56 kDa that was labeled by 3 HatRA, detected by anti-pNP UGT antibody and not present in membranes from nontransfected HK293 cells. Liver microsomes from Gunn rats, which lack UGT1.1, had significant activity toward atRA (111 ± 28 pmol/mg × min).
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