Comparison of substrate metabolism by cytochromes P4502B1, 2B4, and 2B6:: relationship of heme spin state, catalysis, and the effects of cytochrome b5

Comparison of substrate metabolism by cytochromes P4502B1, 2B4, and 2B6:: relationship of heme spin state, catalysis, and the effects of cytochrome b5
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DOI:
10.1016/s0162-0134(02)00597-4
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发表时间:
2003-01-15
影响因子:
3.9
通讯作者:
Hollenberg, PF
Hollenberg, PF
中科院分区:
生物学2区
文献类型:
--
作者:
Reed, JR;Hollenberg, PF

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比较了细胞色素P450(P450)2B1、2B4和2B6对选定底物的代谢,并评价了细胞色素b(5)(b(5))对这些反应的影响。当比较不同P450酶对特定底物的新陈代谢时,b(5)的影响似乎没有任何趋势。还测定了P450酶与底物和细胞色素b(5)相互作用所引起的自旋状态的变化。只有P450 2B4证实了自旋态、反应耦合和b(5)效应之间的关系。这三种酶对苯丙胺和7-乙氧基-4-三氟甲基香豆素的代谢速率可能与高自旋血红素的比例有关。同样,所选底物代谢过程中的反应偶联比例近似等于高自旋P450的比例。数据被解释为表明P450构象。平衡协调调节催化和自旋态的变化。(C)2002 Elsevier Science Inc.保留所有权利。
The metabolism of selected substrates by cytochromes P450 (P450) 2B1, 2B4, and 2B6 was compared, and the effects of cytochrome b(5) (b(5)) on these reactions were assessed. There did not appear to be any trends regarding the effects of b(5) when the metabolism of a given substrate-by the different P450 enzymes was compared. The changes in spin states of the P450 enzymes as a result of interactions with substrates and cytochrome b(5) were also determined. Only P450 2B4 demonstrated a relationship between spin state, reaction coupling and b(5) effects. The rates of benzphetamine and 7-ethoxy-4-trifluoromethylcoumarin metabolism by the three enzymes could be correlated with the proportions of high spin heme. Similarly, the proportion of reaction coupling during the metabolism of selected substrates was approximately equal to the proportion of high spin P450. The data are interpreted to indicate that a P450 conformational. equilibrium coordinately regulates catalysis and spin state changes. (C) 2002 Elsevier Science Inc. All rights reserved.