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Mechanism of molecular multiplicity and genetic deficiency of carbonyl reductase functioning as a drug-metabolizing enzyme

Research Project

Project/Area Number 08672515
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionKumamoto University

Principal Investigator

IMAMURA Yorishige  Kumamoto University, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (30040314)

Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1996: ¥1,600,000 (Direct Cost: ¥1,600,000)
Keywordsdrug-metabolizing enzyme / molecular multiplicity / genetic deficiency / carbonyl reductase / rat liver microsomes / acetohexamide / 20βーヒドロキシステロイド デヒドロゲナーゼ / 遺伝子様式
Research Abstract

The mechanism of molecular multiplicity and genetic deficiency of carbonly reductase functioning as a drug-metabolizing enzyme has been examined. The obtained results are as follows :
1.An enzyme was partially purified from liver microsomes of male rats by using metyrapone as a substrate. The partially purified metyrapone reductase had no ability to reduce acetohexamide. These results indicate that the ketone-reduction of metyrapone and acetohexamide can be catalyzed by different carbonyl reductases.
2.1)A marked strain- and sex-related differences were observed in acetohexamide reductase activity in liver microsomes of rats. However, there was no strain- or sex-related difference of acetohexamide reductase activity in liver cytosol of rats. 2)Treatment with cadmium indirectly decreased acetohexamide reductase activity, which is regulated by androgens, in kidney microsomes of male rats. On the other hand, Cd treatment had no significant effect on acetohexamide reductase activity in kidney cytosol of male rats. The results described in 1)and 2)suggest multiplicity of carbonyl reductase present in rat liver and kidney.
3.A simple Mendelian genetic analysis for the frequency distribution of acetohexamide reductase activity in liver microsomes of male rats provides evidence that the phenotype is genetically regulated by an autosomal co-dominant fashion. Female rats, unlike male rats, did not exhibit microsomal enzyme activity in parental, first filial and second filial generations. Based on these results, it is concluded that the inheritance of the microsomal enzyme activity is sex-limited.
Further studies are in progress to elucidate the mechanism of genetic deficiency of acetohexamide reductase activity in liver microsomes of male rats.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Y.Imamura: "Inheritance of acetohexamide reductase activities in liver microsomes and cytosol of rats" Life Sci.59. 2201-2208 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.lmamura: "Acetohexamide reductase activities in liver microsomes and cytosol of cisplatintreated male rats : Cisplatin indirectly modulates the microsomal enzyme activity" Res.Commun.Mol.Pathol.Pharmacol.94. 203-210 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.lmamura: "Metyrapone reductase purified partially from liver microsomes of male rats : The enzyme differs from acetohexamide reductase" Res.Commun.Mol.Pathol.Pharmacol.95. 219-226 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.lmamura: "Individual variation of acetohexamide reductase activities in liver microsomes and cytosol of rats" Biol.Pharm.Bull.20. 924-926 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.lmamura: "Alteration of acetohexamide reductase activities in kidney microsomes and cytosol of cadmium-treated rats" Toxicol.Lett.(in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Imamura: "Inheritance of acetohexamide reductase activities in liver microsomes and cytosol of rats" Life Sci.59. 2201-2208 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Imamura: "Acetohexamide reductase activities in liver microsomes and cytosol of cisplatin-treated male rats : Cisplatin indirectly modulates the microsomal enzyme activity" Res.Commun.Mol.Pathol.Pharmacol.94. 203-210 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Imamura: "Metyrapone reductase purified partially from liver microsomes of male rats : The enzyme differs from acetohexamide reductase" Res.Commun.Mol.Pathol.Pharmacol.96. 219-226 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Imamura: "Individual variation of acetohexamide reductase activities in liver microsomes and cytosol of rats" Biol.Pharm.Bull.20. 924-926 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Imamura: "Alteration of acetohexamide reductase activities in kidney microsomes and cytosol of cadmium-treated rats" Toxicol.Lett.(in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Imamura: "Metyrapone reductase purified partially from liver microsomes of male rats:The enzyme differs from acetohexamide reductase" Res.Commun.Mol.Pathol.Pharmacol.95・2. 219-226 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Y.Imamura: "Individual variation of acetohexamide reductase activities in liver microsomes and cytosol of rats" Biol.Pharm.Bull.20・8. 924-926 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Y.Imamura: "Carbonyl reductase purified from rabbit liver is not the product of a carbonyl reductase gene (RCBR5 or RCBR6) cloned from the rabbit liver cDNA library" Biol.Pharm.Bull.21・1. 76-78 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Y.Imamura: "Inheritance of acetohexamide reductase activities in liver microsomes and cytosol of rats" Life Sci.59・25. 2201-2208 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Y.Imamura: "Acetohexamide reductase activities in liver microsomes and cytosol of cisplatin-treated male rats" Res.Commun.Mol.Pathol.Pharmacol.94・2. 203-210 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Y.Imamura: "Characterization of acetohexamide reductase purified from rabbit liver,kidney,and heart : Structural requirements for substrates and inhibitors" J.Biochem.121・4. (1997)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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