RETINOID UDP-GLUCURONOSYLTRANSFERASES

视黄醇UDP-葡萄糖醛酸基转移酶

• 批准号: 2905938
• 负责人: Anna Radominska-Pandya
• 金额: $ 22.43万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-01 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2905938
• 关键词: enzyme activity; enzyme substrate complex; glucuronides; glucuronosyltransferase; high performance liquid chromatography; laboratory rabbit; laboratory rat; liver cells; microsomes; molecular cloning; protein isoforms; recombinant proteins; retinoids; site directed mutagenesis; uridine diphosphate; uridine diphosphate glucose

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.

描述：（改编自研究者的摘要） UDP-葡萄糖醛酸基转移酶 (UGT) 是参与以下过程的酶家族： 许多药物和外源化合物的代谢，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，以及参与葡萄糖醛酸化的酶 视黄酸和相关的类维生素A是有限的。 具体来说，身份 尚未确定对类视黄醇具有特异性的 UGT。 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，这项工作将严格检验预测的假设 肝微粒体中存在类维生素A UGT 酶。 假设 它们要么是全新的异构体，要么是现有的 UGT 未确定的类维生素A底物特异性。 为了调查 根据这一假设，提出以下具体目标：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) 识别和 从大鼠肝微粒体组分中分离类维生素A UGT 蛋白；和 3) 鉴定可用的或新型的类维生素A重组UGT同工酶 葡萄糖醛酸化活动。