Deuterium and Tritium Isotope Effects on the Oxidative Demethylation Rate of Methoxychior in Rat Liver Microsomes

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  • ラット肝ミクロゾームにおけるメトキシクロールの酸化的脱メチル化速度に及ぼす重水素およびトリチウム同位体効果
  • ラット肝ミクロゾームにおけるメトキシクロールの酸化的脱メチル化速度に及ぼす重水素およびトリチウム同位体効果〔英文〕
  • ラット カン ミクロゾーム ニ オケル メトキシクロール ノ サンカテキ ダツ

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Apparent deuterium and tritium kinetic isotope effects were measured on the O-demethylation of methoxychlor in uninduced and β-naphthoflavone-induced rat liver microsomes. From the apparent values, the magnitudes of the intrinsic deuterium isotope effect values were calculated by Northrop's method as 15.2 for uninduced and 19.2 for naphthoflavone-induced rat liver microsomes. The large values for the intrinsic isotope effect suggest that the C-H bond cleavage reaction in the O-demethylation catalyzed by microsomal cytochromes P-450 has a linear transition state in which there is no bonding between the carbon and hydrogen atoms. A comparison of the intrinsic isotope effect values with the apparent isotope effect values showed the presence of several partially rate-limiting steps in the O-demethylation of methoxychlor catalyzed by cytochromes P-450.

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