| Project/Area Number |
10672068
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Hokuriku University |
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Principal Investigator |
MATSUNAGA Tamihide Hokuriku University, Faculty of Pharmaceutical Sciences, Lecturer, 薬学部, 講師 (40209581)
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| Co-Investigator(Kenkyū-buntansha) |
USAMI Noriuki Gifu Pharmaceutical University, 薬学部, 助手 (60257483)
WATANABE Kazuhito Hokuriku University, Faculy of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (30113038)
YAMAMOTO Ikuo Hokuriku University, Faculy of Pharmaceutical Sciences, Professor, 薬学部, 教授 (50069746)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1999: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1998: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | 3-OH-β-ionone / 3-oxo-β-ionone / alcohol / ketone / microsomes / dehydrogenase / oxidation / NAD(P) / 脱水素酸化 / NAD / NADP / サル |
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| Research Abstract |
1. 3-OH-β-ionone was oxidized to 3-oxo-β-ionone by hepatic microsomes of mouse and monkey. In both animals, NAD was most effective as cofactor, followed by NADP, NADPH and NADH.
2. The NADPH-dependent 3-oxo-β-ionone forming activity (MALCO activity) in mouse was almost completely inhibited by antibody against Cyp3all.
3-OH-β-ionone MALCO activity in monkey was inhibited by antisera against CYP2A and Cyp3all.
4. The NAD- and NADP-dependent formation of 3-oxa-β-ionone in mouse was inhibited by disulfiram.
5. In the case of monkey, the NADP-dependent activity was inhibited by babital, quercetin and quercitrin as well as disulfiram and HgClィイD22ィエD2, while the NAD-dependent activity was inhibited by disulfiram and HgClィイD22ィエD2.
6. In the hepatic microsomes of monkey, the Km/Vmax value for NAD-dependent 3-oxo-β-ionone forming activity was about 10-fold higher than that for the NADPH-dependent activity.
7. Microsomal 3-OH-β-ionone dehydrogenate (MALDH) was purified from male Japanese monkey livers. Specific activity of the enzyme was about 5 times higher than that of microsomes, and the molecular mass is about 23.5 kDa.
These results indicated that not only P450(MALCO) but also microsomal alcohol dehydrogenase(s) (MALDH) required NAD and/or NADP as cofactor catalyzed the formation of 3-oxo-β-ionone from 3-OH-β-ionone in hepatic microsomes of mouse and monkey.
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