P450 reductase and cytochrome b5 interactions with cytochrome P450: effects on house fly CYP6A1 catalysis.
P450 reductase and cytochrome b5 interactions with cytochrome P450: effects on house fly CYP6A1 catalysis.
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DOI：
10.1016/j.ibmb.2008.08.007
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发表时间：
2008-11
影响因子：
3.8
通讯作者：
Feyereisen, Rene
中科院分区：
文献类型：
--
作者：
Murataliev, Marat B.;Guzov, Victor M.;Walker, F. Ann;Feyereisen, Rene
关键词：
异生物质代谢细胞色素P450系统，CYP 6A 1，P450还原酶，细胞色素b5的蛋白质组分的相互作用，从家蝇（家蝇）的特点。CYP 6A 1活性由CYP 6A 1-P450还原酶复合物的浓度决定，无论哪种蛋白过量存在。holo和apo-b5刺激CYP 6A 1七氯环氧酶和类固醇羟化酶的活性，并影响睾酮羟化的区域选择性。加入apo-b5可降低CYP 6A 1向其P420形式的转化。细胞色素b5的作用可能涉及改变活性位点构象的P450酶的变构修饰。P450反应的总体化学计量是底物依赖性的。观察到CYP 6A 1的高解偶联与过氧化氢的产生，超过伴随的睾酮羟基化或七氯环氧化。包括细胞色素b5在重建系统中提高效率的氧消耗和电子利用NADPH，或耦合的P450反应。根据重组条件，耦合效率从8到25%不等的七氯环氧化，从11到70%的睾酮羟基化。由于CYP 6A 1是一种参与杀虫剂抗性的P450，这表明组成型过表达的P450的异生物质代谢可能与细胞中可能携带健身成本的显著氧化应激有关。
The interactions of protein components of the xenobiotic-metabolizing cytochrome P450 system, CYP6A1, P450 reductase, and cytochrome b5 from the house fly (Musca domestica) have been characterized. CYP6A1 activity is determined by the concentration of the CYP6A1-P450 reductase complex, regardless of which protein is present in excess. Both holo- and apo-b5 stimulated CYP6A1 heptachlor epoxidase and steroid hydroxylase activities and influenced the regioselectivity of testosterone hydroxylation. The conversion of CYP6A1 to its P420 form was decreased by the addition of apo-b5. The effects of cytochrome b5 may involve allosteric modification of the P450 enzyme that modify the conformation of the active site. The overall stoichiometry of the P450 reaction was substrate-dependent. High uncoupling of CYP6A1 was observed with generation of hydrogen peroxide, in excess over the concomitant testosterone hydroxylation or heptachlor epoxidation. Inclusion of cytochrome b5 in the reconstituted system improved efficiency of oxygen consumption and electron utilization from NADPH, or coupling of the P450 reaction. Depending on the reconstitution conditions, coupling efficiency varied from 8 to 25% for heptachlor epoxidation, and from 11 to 70% for testosterone hydroxylation. Because CYP6A1 is a P450 involved in insecticide resistance, this suggests that xenobiotic metabolism by constitutively overexpressed P450s may be linked to significant oxidative stress in the cell that may carry a fitness cost.
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影响因子：
9.8
作者：
ESTABROOK, RW;FRANKLIN, MR;HILDEBRANDT, AG
通讯作者：
HILDEBRANDT, AG
影响因子：
2.9
作者：
Murataliev, MB;Feyereisen, R
通讯作者：
Feyereisen, R
影响因子：
4.1
作者：
Bernhardt, Rita
通讯作者：
Bernhardt, Rita
影响因子：
3.1
作者：
Dunkov, BC;Guzov, VM;Feyereisen, R
通讯作者：
Feyereisen, R
影响因子：
4.8
作者：
Guzov, VM;Houston, HL;Feyereisen, R
通讯作者：
Feyereisen, R