Kinetics of substrate reaction in the course of hydroperoxide-mediated inactivation of cytochrome P450 1A1.
Kinetics of substrate reaction in the course of hydroperoxide-mediated inactivation of cytochrome P450 1A1.
复制标题
氢过氧化物介导的细胞色素 P450 1A1 失活过程中底物反应的动力学。
DOI：
10.1021/bi952396a
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Strobel,HW
中科院分区：
文献类型：
--
作者：
Yu,XC;Liang,C;Strobel,HW
提出了氢过氧化物介导的底物反应和细胞色素 P450 失活的示意性动力学模型。根据该模型，预测了无限时间的产物浓度 (P∞)、P450 失活的表观速率常数 (A) 和底物浓度之间的关系，并对预测结果进行了实验检验。 P∞ 的倒数与 CuOOH 和 H2O2 支持的底物反应中底物浓度的倒数成正比。 P∞的倒数与氢过氧化异丙苯(CuOOH)浓度成正比，但P∞与H2O2浓度无关，表明CuOOH和H2O2对P450失活的影响不同。表观速率常数 (A) 与底物浓度的倒数成正比，表明 P450 的底物保护免受氢过氧化物失活。该模型还表明，第二个 CuOOH 分子可能与底物竞争与 P450 底物结合位点的结合。产物形成与时间的模拟动力学与实验动力学非常一致。
A schematic kinetic model is proposed for the hydroperoxide-mediated substrate reaction and cytochrome P450 inactivation. From the model, the relationships between the product concentration at infinite time (P∞), the apparent rate constant of P450 inactivation (A), and the substrate concentrations are predicted, and the predictions were experimentally examined. The reciprocal ofP∞is proportional to the reciprocal of the substrate concentration in both CuOOH- and H2O2-supported substrate reactions. The reciprocal ofP∞is proportional to cumene hydroperoxide (CuOOH) concentration, butP∞is independent of H2O2concentration, indicating different effects of CuOOH and H2O2in P450 inactivation. The apparent rate constant (A) is proportional to the reciprocal of the substrate concentrations, suggesting substrate protection of P450 from hydroperoxide inactivation. The model also suggests that a second CuOOH molecule may compete with substrate for binding to the P450 substrate binding site. Simulated kinetics of production formation vs time are quite consistent with the experimental kinetics.