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The long-term goal of this project is to develop a reliable and validated method for the determination of glucuronidation activity. The objectives of this project are to characterize UDP glucuronosyltransferases and identify more specific substrates and inhibitors of UDP glucuronosyltransferase activity. The specific aims include: 1) to develop a novel method to quantify UDP glucuronosyltransferase activity and determine the kinetic parameters of UDP glucuronosyltransferase towards phenolic drugs. A rapid and sensitive method will be developed for the quantification of UDP glucuronosyltransferase and the kinetic parameters will be determined. 2) to characterize the UDP glucuronosyltransferases toward various chemicals/drugs and metabolites and determine the reaction specificity towards these substrates. 3) to use the result of specific aim 2 as a guide to determine the inhibitor specificity towards UDP glucuronosyltransferases, to identify more specific substrates towards UDP glucuronosyltransferases and to use these chemical structures for the development of high-throughput screening assays for UDP glucuronosyltransferases. In this project, in vitro and cell-based UDP glucuronosyltransferase assays will be used for the high throughput screening of UDP glucuronosyltransferase substrates in different phases of this research. The result of this project will be novel chemicals and compounds that are substrates for UDP glucuronosyltransferases that can be used for the development of potential drugs. In addition, it will facilitate the study of the mechanism of UDP glucuronosyltransferases and the development of new inhibitors against UDP glucuronosyltransferases. PUBLIC HEALTH RELEVANCE: Relevance to Public Health Glucuronidation is a metabolic pathway for the elimination of many endogenous and exogenous compounds. Glucuronidation is an important mechanism for the disposition of drugs and other therapeutics. This project will evaluate cell-free systems for the quantification of UDP glucuronosyltransferases.Q: What System Requirements: Installation instructions: Features: Support for arbitrary mixtures of omc voices and graphs, support for various model layouts, support for native Java interfaces and Java FX, support for arbitrary bounding volume hierarchies, support for multiple containers, support for variable rotation, support for custom algorithms,
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