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Analyzes of Structure and Function of Novel Carbonyl Metabolic Enzymes : MALDO and MALCO

Research Project

Project/Area Number 06672208
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionHokuriku University

Principal Investigator

YAMAMOTO Ikuo  Hokuriku University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (50069746)

Co-Investigator(Kenkyū-buntansha) USAMI Noriyuki  Hokuriku University, Faculty of Pharmaceutical Sciences, Research Assistant, 薬学部, 助手 (60257483)
MATSUNAGA Tamihide  Hokuriku University, Faculty of Pharmaceutical Sciences, Assistant Professor, 薬学部, 講師 (40209581)
WATANABE Kazuhito  Hokuriku University, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (30113038)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1994: ¥1,600,000 (Direct Cost: ¥1,600,000)
KeywordsAldehyde / Alcohol / Oxygenase / Cannabinoid / Cloning / MALDO / MALCO / P450 / アルコーナ
Research Abstract

Three P450 isozymes, named P450MDX-A,P450GPF-A and P450JM-C,which are major isozymes responsible for 9-anthraldehyde microsomal aldehyde oxygenase (MALDO) activity were purified from hepatic microsomes of mice, guinea pigs and Japanese monkeys. The N-terminal amino acid sequences of these isozymes suggest that the isozymes are member of CYP2B subfamily. Piperonal, alpha-n-amylcinnamaldehyde, vanillin and tolaldehyde were also oxidized to the corresponding carboxylic acids by MALDO of mouse liver.
Three P450 isozymes, named P450MDX-B,P450GPF-B and P450JM-E,which are major isozymes responsible for 7-OH-DELTA^8-tetrahydrocannabinol microsomal alcohol oxygenase (MALCO) activity were purified from hepatic microsomes of mice, guinea pigs and female Japanese monkeys. The N-terminal amino acid sequences of these isozymes suggest that the isozymes are member of CYP3A subfamily.
A cDNA encoding a P450 isozyme was isolated from a cDNA library constructed from male 129 mouse liver. The cDNA,designated Cyp2c-29 (129), may correspond to a polymorphic variant of Cyp2c-29 (isolated from C57BL/6 mouse liver cDNA library). One out of the six nucleotide changes is nonconservative, resulting in the replacement of 106 Ile of Cyp2c-29 (C57BL/6) by 104 Met. The comparison with Cyp2c-29 sequence shows 4 differences concentrated within a 174-nucleotide sequence located 228-405. mRNAs corresponding to this region (188-445) in C57BL/6, ddN,ddY,C3H,DBA/2 and ICR mouse livers were amplified by the methods of RT-PCR.The amplified nucleotide sequences were the identical with those of Cyp2c-29 (129) except for C57BL/6. A cDNA clone encoding P450MDX-B was isolated from a mouse liver cDNA library. The nucleotide sequence of the cDNA is identical to that of Cyp3a-11.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] T.Matsunaga: "cDNA Cloning and Sequence of CYP2C29 Encoding P-450 MUT-2,a Microsomal Aldehyde Oxygenase" Biochim.Biophys.Acta. 1184. 299-301 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K.Watanabe: "Oxidation of Tolualdehyde to Toluic Acid Catalyzed by Cytochrome P450-Dependent Aldehyde Oxygenase in the Mouse Liver" Drug Metab.Dispos.23. 261-265 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K.Watanabe: "3,4,5-Trimethoxyphenylacetaldehyde,an Intermediate Metabolite of Mescaline,is a Substrate of Microsomal Aldehyde Oxygenase in the Mouse Liver" Biol.Pharm.Bull.18. 696-699 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K.Watanabe: "Involvement of CYP2C in the Metabolism of Cannabinoids by Human Hepatic Micromes from an Old Waman" Biol.Pharm,Bull.18. 1138-1141 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Matsunaga: "Metabolism of Δ^9-Tetrahydrocannabinol by cytochrome P450 Isozymes Purified from Hepatic Microsomes of Monkeys" Life Sci.56. 2089-2095 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Matsunaga: "Microsomal Aldehyde Oxygenase (MALDO): Purification and Characterization of a Cytochrome P450 Isozyme responsible for Oxidation of 9-AA to 9-ACA in Monkey Liver" J.Biochem.119. 617-625 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tamihide Matsunaga, Kazuhito Watanabe, Ikuo Yamamoto, Masahiko Negishi, Frank J.Gonzalez and Hidetoshi Yoshimura: "cDNA cloning and sequence of CYP2C29 encoding P-450MUT-2, a microsomal aldehyde oxygenase" Biochim.Biophys.Acta. 1184. 299-301 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kazuhito Watanabe, Junko Kimura, Yasuyuki Iwawaki, Tamihide Matsunaga, Ikuo Yamamoto and Hidetoshi Yoshimura: "Metabolic reaction of tolualdehyde by microsomal aldehyde oxygenase (MALDO) in lung" Jpn.J.Toxicol.Environ.Health. 40. P-10 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kazuhito Watanabe, Tamihide Matsunaga, Ikuo Yamamoto and Hidetoshi Yoshimura: "Oxidation of tolualdehyde to toluic acid catalyzed by cytochrome P450-dependent aldehyde oxygenase in the mouse liver" Drug Metab.Dispos.23. 261-265 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Noriyuki Usami, Yuji Tateoka, Kazuhito Watanabe, Ikuo Yamamoto and Hidetoshi Yoshimura: "Formation of carbon monoxide during mouse hepatic microsomal oxidative metabolism of cannabidiol ; identification and determination" Biol.Pharm.Bull.18. 529-535 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kazuhito Watanabe, Yuichiro Kayano, Tamihide Matsunaga, Ikuo Yamamoto and Hidetoshi Yoshimura: "3,4,5-Trimethoxyphenylacetaldehyde, and intermediate metabolite of mescaline, is a substrate of microsomal aldehyde oxygenase in the mouse liver" Biol.Pharm.Bull.18. 696-699 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tamihide Matsunaga, Yasuyuki Iwawaki, Kazuhito Watanabe, Ikuo Yamamoto, Takashi Kageyama and Hidetoshi Yoshimura: "Metabolism of DELTA^9-tetrahydrocannabinol by cytochrome P450 isozymes purified from hepatic microsomes of monkeys" Life Sci.56. 2089-2095 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kazuhito Watanabe, Tamihide Matsunaga, Ikuo Yamamoto, Yoshihiko Funae and Hidetoshi Yoshimura: "Involvement of CYP2C in the metabolism of cannabinoids by human hepatic microsomes from an old woman" Biol.Pharm.Bull.18. 1138-1141 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kazuhito Watanabe, Tamihide Matsunaga, Ikuo Yamamoto and Hidetoshi Yoshimura: "Involvement of microsomal aldehyde oxygenase (MALDO) in the metabolism of aliphatic aldehydes in the mouse liver" Jpn.J.Environ.Health. 41. P-29 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Ikuo Yamamoto, Katsunori Nagai, Kazuhito Watanabe and Hidetoshi Yoshimura: "A novel metabolite, an oxepin Formed from cannabidiol with guinea-pig hepatic microsomes" J.Pharm.Pharmacol.47. 683-686 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Ikuo Yamamoto, Kazuhito Watanabe, Shizuo Narimatsu and Hidetoshi Yoshimura: " Recent advances in the metabolism of cannabinoids" Int.J.Biochem.Cell Biol.27. 741-746 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hisatoshi Yoshida, Noriyuki Usami, Yasumasa Onishi, Kazuhito Watanabe, Ikuo Yamamoto and Hidetoshi Yoshimura: "Synthesis and pharmacological effects in mice of halogenated cannabinol derivatives" Chem.Pharm.Bull.43. 335-337 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tamihide Matsunaga, Yasuyuki Iwawaki, Kazuhito Watanabe, Ikuo Yamamoto, Takashi Kageyama and Hidetoshi Yoshimura: "Microsomal aldehyde oxygenase (MALDO) : purification and characterization of a cytochrome P450 isozyme responsible for oxidation of 9-anthraldehyde to 9-anthracene carboxylic acid in monkey liver" J.Biochem.119. 617-625 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] I. Yamamoto: "Recent Advances in the Metabolism of Cannabinoids" Int. J. Biochem. Cell Biol. (Mini Review). 27. 741-746 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] I. Yamamoto: "A Nobel Metabolite, an Oxepin Formed from Cannabidiol with Guinea-pig Hepatic Microsomes" J. Pharm. Pharmacol.47. 683-686 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] K. Watanabe: "3,4,5-Trimetoxyphenylacetaldehyde, an Intermediate Metabolite of Mescaline, Is a Substrate for MALDO in the Mouse Liver" Biol. Pharm. Bull.18. 696-699 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] K. Watanabe: "Involvement of CYP2C in the Metabolism of Cannabinoids by Human Hepatic Microsomes" Biol. Pharm. Bull.18. 1138-1141 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] T.Matsunaga: "cDNA Cloning and Sequence of CYP2C29 Encoding p-240 MUT-2,a Microsomal Aldehyde Oxygenase" Biochim.Biophys.Acta. 1184. 299-301 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] K.Watanabe: "Metabolic Reaction of Tolualdehydes by Microsomal Aldehyde Oxygenase (MALDO)in Lung" Jpn.J.Toxicol.Environ.Health. 40. 10 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] K.Watanabe: "Oxidation of Tolualdehydes to Toluic Acide Catalyzed Cytochrome P450-Dependent Aldehyde Oxygenase in Mouse Liver" Drug Metab.Dispos.23. 261-265 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] I.Yamamoto: "A Novel Metabolite,an Oxepin Formed from Cannabidiol with Guinea-Pig Hepatic Microsomes" J.Pharm.Pharmacol.47(in prsee). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] N.Usami: "Formation of Carbon Monoxide During Mouse Hepatic Microsomal Oxidative Metabolism of Cannabidiol,Identification and Determination" Biol.Pharm.Bull.18(in prsee). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] T.Matsunaga: "Metabolism of △^9-Tetrahydrocannabinol by Cytochrome P450 Isozymes Purified from Hepatic Microsomes of Monkeys" Life Sci.(in prsee). (1995)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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