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：（根据调查员的摘要改编） UDP-葡萄糖基转移酶（UGT）是参与该酶的家族 许多药物和异种生物化合物的代谢以及内源性 化合物，例如胆红素，类固醇激素，胆汁酸和甲状腺 激素。 一类重要的生理化合物的信息， 类视网膜类葡萄糖醛酸苷和参与葡萄糖醛酸糖苷的酶 视黄酸和相关的类视黄素受到限制。 具体而言，身份 尚未鉴定出对类视视类动物具有特异性的UGT。 该提案的主要目标之一是阐明 类维生素性葡萄糖醛酸苷的形成和化学结构。 具体而言，这项工作将批判性检验假设，以预测 肝微粒体中类维生素性UGT酶的存在。 它是假定的 它们要么是完全新颖的同工型，要么是现有的UGT 类维生素类似的底物特异性。 为了调查 提出了这一假设，提出了以下特定目标：1）表征 大鼠肝微粒体中的视网膜类似葡萄糖醛酸苷活性； 2）识别和 从大鼠肝微粒体级分中分离出类阳性类ugt蛋白； 3） 确定类维生素类似的可用或新颖的重组UGT同工酶 葡萄糖醛酸化活动。