Increased content of cytochrome P-450 and 4-methylpyrazole binding spectrum after 4-methylpyrazole treatment.
Increased content of cytochrome P-450 and 4-methylpyrazole binding spectrum after 4-methylpyrazole treatment.
复制标题
4-甲基吡唑处理后细胞色素 P-450 和 4-甲基吡唑结合谱的含量增加。
DOI：
10.1016/0006-291x(85)90295-5
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发表时间：
1985
影响因子：
3.1
通讯作者：
Cederbaum,AI
中科院分区：
文献类型：
--
作者：
Feierman,DE;Cederbaum,AI
4-甲基吡唑是乙醇脱氢酶和乙醇代谢的有效抑制剂。在体外，4-甲基吡唑显示出抑制药物和醇的微粒体氧化。以0 - 300 mg/kg体重/天剂量范围内的4-甲基吡唑给药大鼠3天，导致肝微粒体细胞色素P-450含量呈剂量依赖性增加。NADPH-细胞色素P-450还原酶活性无变化。4-甲基吡唑与对照微粒体相互作用产生II型结合光谱，峰位于429 nm，谷位于392 nm。4-甲基吡唑处理后，该光谱变化的幅度增加。动力学实验表明，4-甲基吡唑处理降低了4-甲基吡唑的解离常数（Ks）。最大结合（Vs）增加时，每毫克微粒体蛋白，但不是每nmol细胞色素P-450。因此，4-甲基吡唑处理可以通过多种方式影响微粒体混合功能氧化酶系统，包括与P-450结合以及诱导P-450。
4-Methylpyrazole is a potent inhibitor of alcohol dehydrogenase and of ethanol metabolism. In vitro, 4-methylpyrazole was shown to inhibit microsomal oxidation of drugs and alcohols. Treatment of rats with 4-methylpyrazole at doses ranging from 0 to 300 mg per kg body wt per day for three days resulted in a dose-dependent increase in the content of liver microsomal cytochrome P-450. There was no change in the activity of NADPH-cytochrome P-450 reductase. 4-Methylpyrazole interacted with control microsomes to produce a type II binding spectrum, with a peak at 429 nm, and a trough at 392 nm. The magnitude of this spectral change was increased after 4-methylpyrazole treatment. Kinetic experiments indicated that the 4-methylpyrazole treatment lowered the dissociation constant (Ks) for 4-methylpyrazole. The maximal binding (Vs) was increased when expressed per mg microsomal protein, but not per nmol cytochrome P-450. Therefore, 4-methylpyrazole treatment can affect the microsomal mixed-function oxidase system in several ways, including binding to P-450 as well as inducing P-450.