| Project/Area Number |
60304092
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| Research Category |
Grant-in-Aid for Co-operative Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
物質生物化学
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| Research Institution | Hiroshima University |
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Principal Investigator |
OKUDA Kyuichiro Professor of Department of Biochemistry, School of Dentistry, 歯学部, 教授 (80034156)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEMORI Shigeki Professor of Department of Enviromental Science, Faculty of Integrated Arts and, 総合科学部, 教授 (60019461)
OKAMOTO Mitsuhiro Professor of Department of Biochemistry, School of Medicine Osaka University, 医学部, 教授 (90028613)
ICHIKAWA Yoshiyuki Professor of Department of Biochemistry, Kagawa Medical School, 教授 (60028355)
ISHIMURA Yuzuru Professor of Department of Biochemistry, School of Medicine Keio University, 医学部, 教授 (40025599)
ISHIBASHI Teruo Professor of Department of Biochemistry, School of Medicine Hokkaido University, 医学部, 教授 (60001872)
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| Project Period (FY) |
1985 – 1986
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| Project Status |
Completed (Fiscal Year 1986)
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| Budget Amount *help |
¥5,900,000 (Direct Cost: ¥5,900,000)
Fiscal Year 1986: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1985: ¥3,300,000 (Direct Cost: ¥3,300,000)
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| Keywords | Cytochrome P-450 / Aldosterone / Corticosterone / Vitamin <D_3> / Bile acid / Microsomes / Mitochondria / 水酸化 |
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| Research Abstract |
Cholesterol is synthesized from acetate in the liver and is metabolized to bile acids, corticoids, sexual hormones and vitamin <D_3> in liver, adrenal cortex, sexula glands and skin, respectively. Accordingly, cholesterol is important not only for cell structure and function but also as the source of these hormones and vitamin. However, excess amount of body cholesterol seems to be involved in developing atherosclerosis. The maintenance of a constant level of cholesterol in body is therefore required. Ono et al. and Ishibashi et al. purified squalene epoxidase and lathosterol desaturase, respectively, which are important enzymes for biosynthesis of cholesterol and clarified their properties. Okuda et al. purified cytochrome P-450 catalyzing 7 <alpha> -hydroxylation of cholesterol, which is a rate limiting step of cholesterol catabolism to bile acids.
Steroid hormones such as corticoids and sexual hormones are inter-converted into active or inactive forms in target organs or in liver and
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their cellular levels are strictly controlled. It is important to maintain the balance in production of these steroid hormones for homeostasis of organisms. Imbalance of these hormone production leads to severe diseases. Okamoto et al. found that corticosterone is converted to aldosterone by P- <450_(11beta)> and Ishimura et al. located P- <450_(11beta)> and P- <450_(scc)> in adrenal mitochondria by a histochemical technique using HRP and studied the mechanism of functional zonation. Horie et al. and Ichikawa et al. observed the multiplicty of cytochromes P-450 in adrenal mitochondria. Takemori et al. studied the mechanism of interaction between P-450 and steroid substrates using liposomes. Shimizu et al. partially purified the enzyme which is involved in biosynthesis of <DELTA^(19)> - <C_(21)> steroid from swine testes and Nakajin et al. found that cytochrome <b_5> is required in this reaction. Yoshida et al. studied the reaction mechanism of 14-demethylation of lanosterol using the purified <P-450_(14DM)> . Tamaoki et al. established the involvement of lysine in the reaction of NADPH-cytochrome P-450 reductase wih NADPH using an affinity labeling technique. Less
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