Cytochrome P4502D isozymes catalyze the 4-hydroxylation of methamphetamine enantiomers.
Cytochrome P4502D isozymes catalyze the 4-hydroxylation of methamphetamine enantiomers.
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发表时间：
1995-06
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通讯作者：
L. Lin;Y. Kumagai;A. Hiratsuka;S. Narimatsu;T. Suzuki;Y. Funae;E. Distefano;A. Cho
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作者：
L. Lin;Y. Kumagai;A. Hiratsuka;S. Narimatsu;T. Suzuki;Y. Funae;E. Distefano;A. Cho
在Sprague-Dawley和Dark Agglutinus品系大鼠肝微粒体中检测了S（+）-和R（-）-甲基苯丙胺的4-羟基化，以确定细胞色素P4502 D（CYP 2D）亚家族同工酶在催化反应中的作用。在该研究中，发现抗P450-BTL IgG、丁呋洛尔和奎宁（分别为CYP 2D同工酶的底物和抑制剂）可阻断Sprague-Dawley大鼠微粒体催化的约90%的反应。从大鼠肝微粒体中纯化的CYP 2D同工酶的重建系统也介导了该反应。这些观察结果和在黑Agglutinin大鼠微粒体中发现的最小活性支持了甲基苯丙胺与其他苯基异丙胺化合物一样在芳环的4位被CYP 2D同工酶氧化的观点。
The 4-hydroxylation of S(+)- and R(-)-methamphetamine by rat liver microsomes was examined in Sprague-Dawley and Dark Agouti strains to determine the role of cytochrome P4502D (CYP2D) subfamily isozymes in catalyzing the reaction. In the study, anti-P450-BTL IgG, bufuralol, and quinine, a substrate and inhibitors of CYP2D isozymes, respectively, were found to block approximately 90% of the reaction as catalyzed by microsomes from Sprague-Dawley rats. Reconstituted systems of CYP2D isozymes purified from rat liver microsomes also mediated the reaction. These observations and the minimal activity found in microsomes from Dark Agouti rats support the notion that methamphetamine, like other phenylisopropylamine compounds, is oxidized on the 4-position of the aromatic ring by CYP2D isozymes.