エタノールによるチトクロームＰ‐４５０依存性薬物水酸化反応抑制メカニズムに関する検討

DOI Web Site Web Site

書誌事項

タイトル別名
  • Study on inhibition of cytochrome P-450-dependent mixed function oxidation by ethanol
  • エタノール ニヨル チトクローム P 450 イゾンセイ ヤクブツ スイサンカ

この論文をさがす

抄録

The cytochrome P-450 in liver microsome catalyzes the drug oxidation by using oxygen and NADPH. We have investigated the mechanism on the inhibition of cytochrome P-450-dependent mixed function oxidation by ethanol.<BR>NADPH oxidation decreased with increasing ethanol concentration in liver microsomes. Ethanol induced a reverse type I binding spectrum, and competitively inhibited the binding of hexobarbital to liver microsome due to the displacement of the endogeneous substrate.<BR>The NADPH-dependent reduction of liver microsomal cytochrome P-450 was biphasic and composed of two concurrent first-order reactions. The addition of hexobarbital increased the both rate constant for the fast and slow phase. The rate constant for the fast phase was decreased by the addition of ethanol, but the rate constant for the slow phase remained unchanged. Therefore, the inhibition of mixed function oxidation by ethanol may be due partly to the decrease of NADPH-cytochrome P-450 reductase activity resulting from the decrease of substrates bound to cytochrome P-450 by ethanol.

収録刊行物

  • 肝臓

    肝臓 23 (2), 109-115, 1982

    一般社団法人　日本肝臓学会

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ