Role of Quinone-Metabolizing Enzymes on the Toxicities of Quinone Derivatives.
| Project/Area Number |
03671044
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | Chiba University |
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Principal Investigator |
UNEMOTO Tsutomu Chiba University, Faculty of Pharmaceutical Sciences Professor, 薬学部, 教授 (30089601)
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| Co-Investigator(Kenkyū-buntansha) |
HAYASHI Maki Chiba University, Faculty of Pharmaceutical Sciences Associate Professor, 薬学部, 助教授 (50092086)
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| Project Period (FY) |
1991 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1992: ¥300,000 (Direct Cost: ¥300,000)
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| Keywords | NADH-quinone reductase / NADPH-quinone reductase / DT-diaphorase / Quinone metabolism / Induction / 2-Methylene-4-butyrolactone / Quinone toxicity / Escherichia coli / NADHーguinone reductase / メナジオン / 誘導基質 / キノン化合物 |
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| Research Abstract |
An FMN-dependent NADH-quinone reductase is induced in Escherichia coli by growing the cells in the presence of menadione. Since the properties of induced enzyme are very similar to those of DT-diaphorase from animal cells, structural requirements of quinone derivatives as an inducer of NADH-quinone reductase in E. coli were examined. It was found that 2-alkyl-1,4-quinone structure with C-3 unsubstituted or substituted with Br is critical asa common inductive signal. Michael reaction acceptors, known as strong inducers of DT-diaphorase in mouse hepatoma cells, were not always effective inducers in E. coli. However 2-methylene-4-butyrolactone, methylacrylate and methyl vinyl ketone were found to induce NADPH-quinone reductases in addition to NADH- quinone reductases. These induced quinone reductases reduced several quinone derivatives by the two-electron reduction pathway without generating semiquinone radicals. Therefore, the induction of these enzymes were considered to minimize the generation of free radicals during the metabolism quinone derivatives. Since the small amounts of induced enzymes present in the non-induced cells, it is necessary to make clear the physiological functions of these enzymes in E. coli.
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Report
(3 results)
Research Products
(4 results)
