| 摘要 | 第3-7页 |
| abstract | 第7-9页 |
| Chapter1 Introduction | 第13-25页 |
| 1.1 Uridine diphosphate-glucuronosyltransferases(UGTs) and their functions | 第13-14页 |
| 1.2 Nomenclature and distribution of UGTs superfamily | 第14-17页 |
| 1.2.1 Nomenclature of22 human UGTs | 第14-15页 |
| 1.2.2 Differences in substrates of four UGT families | 第15-16页 |
| 1.2.3 N-glucuronidation by UGTs | 第16页 |
| 1.2.4 Tissue localization | 第16-17页 |
| 1.3 Diseases and drug-drug interaction related to UGTs | 第17-20页 |
| 1.3.1 Drug-drug interaction | 第17-19页 |
| 1.3.2 UGTs mutation related diseases | 第19-20页 |
| 1.4 Different methods to study UGTs function | 第20-21页 |
| 1.4.1 Human liver microsomes and whole cell biotransformation | 第20-21页 |
| 1.4.2 Enzyme bags | 第21页 |
| 1.5 Homology modeling and molecular docking | 第21-22页 |
| 1.6 UGT mediated doping compounds glucuronidation | 第22-25页 |
| 1.6.1 Doping compounds prohibited by World Anti-doping Agency | 第23-24页 |
| 1.6.2 Analysis of propranolol and its glucuronide | 第24-25页 |
| Chapter2 Materials and Methods | 第25-39页 |
| 2.1 Materials | 第25-28页 |
| 2.2 Instruments and consumables | 第28-30页 |
| 2.3 Methods | 第30-39页 |
| 2.3.1 Fission yeast strains and media | 第30-32页 |
| 2.3.2 Enzyme bags method | 第32-33页 |
| 2.3.3 Comparison between human liver microsomes and enzyme bags when treated with Triton X-100 | 第33-34页 |
| 2.3.4 Direct comparison of UGT1A9 activity in whole-cell biotransformation and enzyme bag-catalyzed bioconversion | 第34页 |
| 2.3.5 Glucuronides of propranolol and 4-hydroxypropranolol analysis by enzyme bags method | 第34-35页 |
| 2.3.6 LC/MS analysis | 第35页 |
| 2.3.7 Bioluminescence detection | 第35-36页 |
| 2.3.8 Statistical analysis | 第36-37页 |
| 2.3.9 Homology modeling and molecular docking | 第37-39页 |
| Chapter3 Results | 第39-57页 |
| 3.1 Effect of Triton X-100 on UGT activity in human liver microsomes and enzyme bags | 第39-40页 |
| 3.2 Direct comparison of UGT1A9 activity in whole-cell biotransformation and enzyme bag-catalyzed bioconversion | 第40-41页 |
| 3.3 Long time storage of enzyme bags | 第41-42页 |
| 3.4 Identification of new UGT probe reactions | 第42-43页 |
| 3.5 Enzyme bag-based inhibition assay | 第43-44页 |
| 3.6 UGT-dependent production of glucosides | 第44-45页 |
| 3.7 Bioinformatic analysis of UGT1A5 missense variants and activity comparison of different UGT1A5 haplotypes | 第45-48页 |
| 3.8 Homology modeling and molecular docking for UGT1A | 第48-54页 |
| 3.8.1 Homology modeling | 第48-50页 |
| 3.8.2 Comparative molecular dynamics simulations of UGT1A5*1 and UGT1A5*8 | 第50-53页 |
| 3.8.3 Substrate docking experiments for UGT1A | 第53-54页 |
| 3.9 Glucuronides of propranolol and 4-hydroxypropranolol analysis by enzyme bags method | 第54-57页 |
| Chapter4 Discussion | 第57-65页 |
| 4.1 Effect of Triton X-100 on UGT activity in human liver microsomes and enzyme bags | 第57-58页 |
| 4.2 Direct comparison of UGT1A9 activity in whole-cell biotransformation and enzyme bag-catalyzed bioconversion | 第58-59页 |
| 4.3 Long time storage of enzyme bags | 第59页 |
| 4.4 Identification of new UGT probe reactions | 第59-60页 |
| 4.5 Enzyme bag-based inhibition assay | 第60-61页 |
| 4.6 UGT-dependent production of glucosides | 第61-62页 |
| 4.7 Homology modeling and molecular docking for UGT1A5 variants | 第62页 |
| 4.8 Glucuronides of propranolol and 4-hydroxypropranolol analysis by enzyme bags method | 第62-65页 |
| Chapter5 Conclusions and Perspectives | 第65-67页 |
| Chapter6 References | 第67-87页 |
| Chapter7 Appendices | 第87-91页 |
| Chapter8 Notes on publications and participation in scientific research | 第91-93页 |
| Chapter9 Acknowledgements | 第93页 |
