| Project/Area Number |
60870012
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| Research Category |
Grant-in-Aid for Developmental Scientific Research
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| Allocation Type | Single-year Grants |
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| Research Field |
General medical chemistry
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| Research Institution | Kyoto University |
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Principal Investigator |
ORII Yutaka (1987) Faculty of Medicine, Kyoto University, 医学部, 助教授 (60028149)
佐野 晴洋 (1985-1986) 京大, 医学部, 教授 (60025533)
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| Co-Investigator(Kenkyū-buntansha) |
SANO Seiyo Shiga University of Medical Science, 学長 (60025533)
KAWANISHI Shosuke Faculty of Medicine, Kyoto University, 医学部, 講師 (10025637)
折井 豊 京都大学, 医学部, 助教授 (60028149)
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| Project Period (FY) |
1985 – 1987
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| Project Status |
Completed (Fiscal Year 1987)
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| Budget Amount *help |
¥12,000,000 (Direct Cost: ¥12,000,000)
Fiscal Year 1987: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1986: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1985: ¥8,000,000 (Direct Cost: ¥8,000,000)
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| Keywords | P-450 / <alpha>-oxyprotoheme / Fe(II)-oxyprotoporphyrin <pi>-neutral radical / Fe(I)-protoporphyrin protoheme-n-butylmercaptide / 高速酸素混合装置 / P-450 / プロトヘムーn-ブチルメルカプチド / オキセン / オキシゲナーゼ / ビリルビン / ビリベルジン / ミオグロビン / プロトヘム-1,2-ジメチルイミダゾール錯体 / α-オキシヘムπ-中性ラジカル / 鉄1価化合物 / 【P_(450)】モデル |
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| Research Abstract |
Heme catabolism in an important biological process, which is caralyzed by the enzyme heme oxygenase. P-450 is involved in the hydroxylation of steroids, alkanes and in the metabolism of various drugs. <alpha>-Oxprotoheme, in early intermediate in heme catabolism, was synthesized and its autoxidation to biliverdin IX<alpha> was studied using rapid mixing sampling apparatus. The apparatus was prepared for mixing two different samples anaerobically or aerobically below -10゜C, followed by recording electronic spectra and ESR spectra. The experiment demonstrate severel lives of evidence for a unique electronic structure of <alpha>-oxyprotoheme, which is a resonance hybrid between Fe(II)-oxyprotoporphyrin <pi>-neutral radical and Fe(III)-oxyprotorphyrin anion. The data for Fe(III)-oxyprotoporphyrin in basic solvent are consistent with the fromulation of Fe(II)-oxyprotorphyrin <pi>-neutral radical, in which the hydroxy proton is deprotonated to afford theenolate from, therby electron transfer occurring from the enolate anion to the ferric iron to form the Fe(II)-oxyprotoporphyrin <pi>-neutral radical. Such resonance structures depends on the ligand basicity. It is interesting to note that the ESR spectrum of Fe(II)-oxyprotoporphyrin <pi>-neutral radical in basic solvent such as 4-acetylpyridine is quite similar to that for Fe(I)-protoporphyrin which lead us to propose in our prevoius report that cooling to 77K causes one more electron transfer from the porphyrin to Fe(II) to form at Fe(I) compound. In P-450 model system (protoheme-n-butylmercaptide), however, ESR spectrum was silent and showed no Fe(i) spectra which demonstrated one electron transfer from S^- to Fe(II). Instead high oxidation state of Fe(IV) was demonstrated.
Using a rapid mixing sampling apparatus, the novel 893 nm intermediate was detected with halflife time of 300 ms during the conversion of <alpha>-oxyprotoheme to <alpha>-versohemochrome.
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