Differential glucuronidation of bile acids, androgens and estrogens by human UGT1A3 and 2B7

Walter E. Gall, Gregory Zawada, Behnaz Mojarrabi, Thomas R. Tephly, Mitchell D. Green, Birgit L. Coffman, Peter I. Mackenzie, Anna Radominska-Pandya

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    135 Citations (Scopus)

    Abstract

    In this work, UDP-glucuronosyltransferases (UGTs), UGT1A3, 2B7(H268) and 2B7(Y268), stably expressed in human embryonic kidney cells (HK293) were used to assess glucuronidation activities with a variety of steroid hormone and bile acid substrates. The rate of synthesis of carboxyl- and hydroxyl-linked glucuronides was determined under optimal reaction conditions. Expressed UGT1A3 catalyzed bile acid glucuronidation at high rates exclusively at the carboxyl moiety for all compounds tested. In contrast, UGT1A4 catalyzed bile acid glucuronidation at very low rates exclusively at the 3α-hydroxyl function. Both UGT2B7 allelic variants glucuronidated the bile acid substrates at both carboxyl and hydroxyl moieties, however, the 3α-hydroxyl position was preferentially conjugated compared to the carboxyl function. Similarly, androsterone, a 3α-hydroxylated androgenic steroid, was glucuronidated at very high rates by expressed UGT2B7. Of the estrogenic compounds tested, UGT2B7 catalyzed the glucuronidation of estriol at rates comparable to those determined for androsterone. Other structural discrimination was found with UGT2B7 which had activity toward estriol and estradiol exclusively at the 17β-OH position, yielding the cholestatic steroid D-ring glucuronides. Copyright (C) 1999 Elsevier Science Ltd.

    Original languageEnglish
    Pages (from-to)101-108
    Number of pages8
    JournalJournal of Steroid Biochemistry and Molecular Biology
    Volume70
    Issue number1-3
    DOIs
    Publication statusPublished - Jul 1999

    Keywords

    • Androgens and estrogens
    • Bile acids
    • Glucuronidation
    • UDP-glucuronosyltransferase

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  • Cite this

    Gall, W. E., Zawada, G., Mojarrabi, B., Tephly, T. R., Green, M. D., Coffman, B. L., Mackenzie, P. I., & Radominska-Pandya, A. (1999). Differential glucuronidation of bile acids, androgens and estrogens by human UGT1A3 and 2B7. Journal of Steroid Biochemistry and Molecular Biology, 70(1-3), 101-108. https://doi.org/10.1016/S0960-0760(99)00088-6