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1988 Fiscal Year Final Research Report Summary

Correlation of Heme-environment Structure of Protein Moiety with Kinetic Properties and Physiological Functions in Various Peroxidases

Research Project

Project/Area Number 62580107
Research Category

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

Allocation TypeSingle-year Grants
Research Field 物質生物化学
Research InstitutionFaculty of Pharmaceutical Sciences, Chiba University

Principal Investigator

HOSOYA Toichiro  Professor,Faculty of Pharmaceutical Sciences, Chiba University, 薬学部, 教授 (10019648)

Co-Investigator(Kenkyū-buntansha) TAKAHASHI Seizo  Associate Professor,Faculty of Domestic Science, Japan Women's University, 家政学部, 助教授 (00011693)
SUZUKI Noriaki  Research Assistant Faculty of Pharmaceutical Sciences, ChibaUniversity, 薬学部, 助手 (10171240)
Project Period (FY) 1987 – 1988
Keywordsperoxidase / horseradish peroxidase / thyroid peroxidase / lactoperoxidase / NMR / optical difference spectrum / HOMO energy / カップリング活性
Research Abstract

^1H-NMR and ^<127>I-NMR studies indicated that I^- binds to horseradish peroxidase (HRP) at most equal distance from the heme-perypheral 1- and 8-methyl groups at the distal side of the heme and the interaction becomes stronger in acidic medium with protonation of the ionizable group with the PK_a values of 4.0. While, ^1H-NMR and optical difference studies indicated that I^- binds to lacto-peroxidase (LPO) outside the heme crevice but at the position close enough to interact with the distal histidine residue which possibly mediates electron transfer in the iodide oxidation reaction.
These differences in the two enzymes may be intimately related to the change in the ability of iodide oxidation. On the other hand, correlation of the rate of electron transfer from the second substrates (phenol- and aniline-derivatives) to HRP compound II with electronic states of these substrates calculated by molecular orbital methods indicated that the transfer of electron may occur from HOMO energy level of the substrates, suggesting the importance of interaction.
As for thyroid peroxidase (TPO), an improved assay method for the activity of coupling of iodo-tyrosyl residues of thyroglobulin (Tg) has been established and applied to human thyroid tissues with various diseases. Comparison of these enzymes (TPO, LPO and HRP) with respect to coupling activity as well as peroxidase activity demonstrated that TPO is the most active enzyme, in accordance with physiological functions. In sera of patients with autoimmune thyroid diseases, we found also the presence of anti-TPO autoantibodies and that these autoantibodies recognize common epitopes of TPO and Tg, which may be related to the causes of autoimmune thyroiditis.

  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Junji Sakurada,;Seizo Takahashi,;Toichiro Hosoya.: Journal of Biological Chemistry. 262. 4007-4010 (1987)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] J.Sakurada,;S.Takahashi,;T.Shimizu,;M.Haatano,;T,Hosoya.: Biochemistry. 26. 6478-6483 (1987)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Kohno,;N.Naito,;K.Saito,;O.Tarutani,;H.Nakajima,;T.Hosoya.: Acta Paediatrica Japonica. 30(Suppl). 128-132 (1988)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] J.Takamatsu,;T.Hosoya,;N.Naito,;H.Yoshimura,;Y.Kohno,;O.Tarutani,;K.Kuma,;S.Saito,;K.Takeda,;T.Mozai.: Journal of Clinical Endocrinology and Metabolism. 66. 147-152 (1988)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 樽谷修、阿部展祐輝、石田常博、泉雄勝、高橋禮子、齋藤公幸、河野陽一、桧山義雄、吉村公一、細谷東一郎: 日本内分泌学会雑誌. 64. 390-401 (1988)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Yoshimura,;K,Ito,;O.Taratani.;T.Hosoya.: Acta Endocrinlolgia(Copenh). 118. 147-153 (1988)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] J.Sakurada,;M.Aida,;C.Nagata,;T.Hosoya.: Journal of Biological Physics. 16. 17-23 (1988)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Kohno,;N.Naito,;Y.Hiyama,;N.Shimojo,;N.Suzuki,;O.Tarutani,;H,Niimi,;H.Nakajima,;T.Hosoya.: Journal of Clinical Endocrinology and Metabolism. 67. 899-907 (1988)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 尾崎修武、鈴木章、八代亨、真鍋嘉尚、伊藤国彦、大森毅、細谷東一郎: 内分泌外科. 5. 237-241 (1988)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Hosoya,;J.Sakurada,;C.Kurokawa,;R.Toyoda,;S.Nakamura.: Biochemistry. 28. (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Ohmori,;O.Taratani,;T.Hosoya.: Biochemical Journal. (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Yoshimura,;O.Ozaki,;K.Ito,;T.Hosoya.: Endocrinologia Japonica. 36. (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 細谷東一郎: "活性酸素、生物での生成・消去・作用の分子機構(蛋白質核酸酵素 臨時増刊 Vol.33 No.16)のうち「ペルオキシダーゼ」" 共立出版株式会社, 3042-3047 (1988)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Junji Sakurada; Seizo Takahashi; Toichiro Hosoya: "Proton nuclear magnetic resonance studies on the iodine binding by horseradish peroxidase" Journal of Biological Chemistry. 262. 4007-4010 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Junji Sakurada; Seizo Takahashi; Toru Shimizu; Masahiro Hatano; Toichiro Hosoya: "Proton and iodine-127 nuclear magnetic resonance studies on the binding of iodine by lactoperoxidase" Biochemistry. 26. 6478-6483 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoichi Kohno; Naokazu Naito; Kimiyuki Saito; Osamu Tarutani; Hironori Nakajima; Toichiro Hosoya: "Anti-thyroglobulin antibodies in patients with chronic thyroiditis and in healthy subjects" Acta Paediatrica Japonica. 128-132 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Junta Takamstsu; Toichiro Hosoya; Naokazu Naito; Hirokatsu Yoshimura; Yoichi Khono; Osamus Tarutani; Kanji Kuma; Sadaki Sasane; Kyoto Takesa; Toshiji Mozai: "Enhanced thyroid iodine metabolism in patients with triiodothyronine-predominant graves' Disease" Journal of Clinical Endocrinology and Metabolism. 66. 147-152 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Osamu Tarutani; Nobuyuki Abe; Tsunehiro Ishisa; Masaru Izuo; Noriko Takahashi; Kimiyuki Saio; Yoichi Kohno; Yoshio Hiyama; Hirokatsu Yoshimura; Toichiro Hosoya: "Characterication of thyroglobulin and thyroid peroxidase activity in patients with functioning thyroid benign Tumors" Folia Endocrinologia. 64. 390-401 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hirokatsu Yoshimura; Kunihiko Ito; Osamu Tarutani; Toichiro Hosoya: "Peroxidase activity and thyroglobulin iodination activity of thyroid peroxidase in non-functioning thyroid tumours" Acta Endocrinologia (Copenh). 118. 147-153 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Junji Sakurada; Misako Aida; Chikayoshi Nagata; Toichiro Hosoya: "Molecular orbital studies of the action of thyroid hormone analogs: Effects on oxygen comsumption of mitochondria and horseradish peroxidasecatalyzed NADH oxidation" Journal of Biological Physics. 16. 17-23 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoichi Kohno; Naokazu Naito; Yoshio Hiyama; Naoki Shimojo; Noriaki Suzuki; Osamu Tarutani; Hiroo Niimi; Hironori Nakajima; Toichiro Hosoya: "Thyroglobulin and thyroid peroxidase share common epitopes recognized by autoantibodies in patients with chronic autoimmune thyroiditis" Journal of Clinical Endocrinology and Metabolism. 67. 899-907 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Osamu Ozaki; Akira Suzuki; Toru Yashiro; Yoshiaki MAnabe; Kunihiko Ito; Takeshi Ohmori; Toichiro Hosoya: "Significant difference in the response to anti-thyroid drug between the two lobes of Graves' thyroid" Endocrine Surgery. 5. 237-241 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Toichiro Hosoya; Junji Sakurada; Chisato Kurokawa; Rie Toyoda; Shingo Nakamura: "Interaction of aromatic donor molecules with lactoperoxidase probed by optical difference spectra" Biochemistry. 28. (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takeshi Ohmori; Osamu Tarutani; Toichiro Hosoya: "Improved assay method for activity of thyroid peroxidase-catalyzed coupling of iodotyrosyl residues of thyroglobulin utilizing high performance liquid chromatogarphy for analysis of iodothyronines" Biochemical Journal. (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hirokatsu Yoshimura; Osamu Ozaki; Kunihiko Ito; Toichiro Hosoya: "Peroxidase activities in autonomusly functioning nodules and the adjacent normal portion of thyroids" Endocrinologia Japonica. 36. (1089)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1990-03-20  

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