RETINOID UDP-GLUCURONOSYLTRANSFERASES

描述：(改编自调查员摘要) UDP-葡萄糖醛酸基转移酶(UGT)是一类参与细胞周期调控的酶。 许多药物和外来化合物的代谢，以及内源性的 胆红素、类固醇激素、胆汁酸和甲状腺等化合物 荷尔蒙。关于一类重要的生理化合物的信息， 维甲酸葡萄糖醛酸苷，以及参与葡萄糖醛酸化反应的酶 维甲酸和相关的维甲酸是有限的。具体地说，身份 其中对维甲酸具有特异性的UGT尚未被鉴定。 这项提议的主要目标之一是阐明 维甲酸葡萄糖醛酸类化合物的形成和化学结构。 具体地说，这项工作将对预测 肝微粒体中存在类维甲酸UGT酶。这是假定的 它们要么是全新的异构体，要么是现有的UGT 维甲酸的底物专一性不明。为了调查 这一假设，提出了以下具体目的：1)表征 大鼠肝微粒体维甲酸葡萄糖醛酸化活性；2)鉴定和 从大鼠肝微粒体中分离维甲酸UGT蛋白(S)；3) 鉴定现有的或新的重组维甲酸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.