Study on the mechanism of biosynthesis of 19-nor-stenroids and its application for analysis of pathgeneeis
| Project/Area Number |
60571109
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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 |
Laboratory medicine
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| Research Institution | Kobe Women's College of Pharmacy |
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Principal Investigator |
WATANABE Fukuko Kobe Women's College of Pharmacy, Faculty of Pharmacy, Professor, 薬学部, 教授 (10068322)
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| Co-Investigator(Kenkyū-buntansha) |
NINOMIYA Ichiya Kobe Women's College of Pharmacy, Faculty of Pharmacy, Professor, 薬学部, 教授 (00068321)
山永 弘乃 神戸女子薬科大学, 薬学部, 助手
NISHIGUCHI Yoshino Kobe Women's College of Pharmacy, Faculty of Pharmacy, Assistant, 薬学部, 助手
KOBAYASHI Yoshiharu Kobe Women's College of Pharmacy, Faculty of Pharmacy, Looturer, 薬学部, 講師 (20133647)
YAMANAGA Hirono Kobe Women's College of Pharmacy, Faculty of Pharmacy, Assistant
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| Project Period (FY) |
1985 – 1987
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| Project Status |
Completed (Fiscal Year 1987)
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| Budget Amount *help |
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1987: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1986: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1985: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | 11-Deoxycorticosterone(DOC) / Adrenal cortex mitochondri fraction / 19-Position oxidation reaction / Cytochrome P_<450> / 19-OH-DOC / 19-oxo-DOC / 19oic-DOC / 19-ノル型ステロイド / デオキシコルチコステロン / ウシ副腎皮質ミトコンドリア / シトクロム【P_(450)】 |
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| Research Abstract |
We have demonstrated the presence of an alternative metabolic pathway of 11-deoxycorticosterone(DOC) in bovine adrenal cortex in vitro: DOC---19-OH-DOC---19-oxo-DOC---19-oic-DOC.
Comparative studies of 11<beta>-, 18-, and 19-hydroxylation activities of reveled that an appreciable level of hydroxylation rate was observed in 19-hydroxylation of DOC, as well as in 11<beta>-, and 18-hydroxylations. In addition,the rates of the oxidation reactions of 19-OH-DOC and 19-oxo-DOC at the 19-position were about 5 times higher than those of the 19-hydroxylation of DOC. These resultus suggest the presence of the pathway of the C-19 oxidation of DOC, although the affinities of 19-OH-DOC and 19oxo-DOC for the enzyme(s) were lower than that of DOC.
It was also established that reduced pyridine nucleotibe(NADPH) and molecular oxygen were required for these oxidation reactions. In addition, these three oxidation reactions were uniformly inhibited by the presence of carbon monoxide or metyrapone(0.01-1.0<micrn>M), which is known to bind Specifically with cytochrome P-450, while potassium cyanide(0.01-0.1mM) did not affect them. These results suggest the possibility of the inbolbe-ment of cytochrome P-450 in the C-19 oxidation reactions of DOC,19-OH-DOC and 19-oic-DOC. We have also shown that 19-oic-DOC is the final product of the metabolism of DOC in the adrenal gland and that it may further be converted to 19-nor-DOC extraadrenally.
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Report
(2 results)
Research Products
(6 results)
