| Project/Area Number |
62580107
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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 |
物質生物化学
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| Research Institution | Faculty of Pharmaceutical Sciences, Chiba University |
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Principal Investigator |
HOSOYA Toichiro Professor,Faculty of Pharmaceutical Sciences, Chiba University, 薬学部, 教授 (10019648)
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| 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)
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| Project Period (FY) |
1987 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1988: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1987: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | peroxidase / horseradish peroxidase / thyroid peroxidase / lactoperoxidase / NMR / optical difference spectrum / HOMO energy / カップリング活性 / 甲状腺ホルモン合成 / 橋本病 / バセドウ病 / HOMO / エネルギーレベル / 化学修飾 / 差スペクトル / 自己抗体 |
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| 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.
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