RETINOID UDP-GLUCURONOSYLTRANSFERASES

描述：（改编自研究者摘要） UDP-葡糖醛酸基转移酶（UGT）是参与葡萄糖醛酸转移酶的酶家族。 许多药物和异生物质化合物的代谢，以及内源性 化合物，如胆红素、类固醇激素、胆汁酸和甲状腺 荷尔蒙 关于一类重要的生理化合物的信息， 类维生素A葡萄糖醛酸苷和参与葡萄糖醛酸化的酶 视黄酸和相关的类视黄酸是有限的。 具体来说，身份 对类维生素A具有特异性的UGT尚未被鉴定。 该提案的主要目标之一是阐明 类维生素A葡萄糖醛酸苷的形成和化学结构。 具体来说，这项工作将严格测试的假设预测 肝微粒体中存在类维生素A UGT酶。 据推测 它们要么是全新的亚型，要么是现有的UGT中的一种， 未鉴定的类维生素A底物特异性。 为了研究 这一假设，提出了以下具体目标：1）表征 大鼠肝微粒体中的类维生素A葡萄糖醛酸化活性; 2）鉴定和 从大鼠肝微粒体部分分离类维生素A UGT蛋白;和3） 鉴定类维生素A可用或新的重组UGT同工酶 葡萄糖醛酸化活性。

DESCRIPTION: (Adapted from investigator's abstract) The UDP-glucuronosyltransferases (UGTs) are a family of enzymes involved in the metabolism of many drugs and xenobiotic compounds, as well as endogenous compounds, such as bilirubin, steroid hormones, bile acids, and thyroid hormones. Information on one important class of physiological compounds, retinoid glucuronides, and the enzymes involved in the glucuronidation of retinoic acid and related retinoids is limited. Specifically, the identity of the UGTs that have specificity toward retinoids have not been identified. One of the principal goals of this proposal is to elucidate mechanisms of formation and the chemical structures of the retinoid glucuronides. Specifically, this work will critically test the hypothesis predicting the presence of retinoid UGT enzymes in hepatic microsomes. It is postulated that they are either entirely novel isoforms or among the existing UGTs with unidentified substrate specificity for retinoids. In order to investigate this hypothesis, the following specific aims are proposed: 1) characterize retinoid glucuronidating activity in rat liver microsomes; 2) identify and isolate retinoid UGT protein(s) from rat liver microsomal fractions; and 3) identify available or novel recombinant UGT isoenzymes for retinoid glucuronidation activities.