The relationships between cytochromes P450 and H(2)O(2): Production, reaction, and inhibition.
The relationships between cytochromes P450 and H(2)O(2): Production, reaction, and inhibition.
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DOI：
10.1016/j.jinorgbio.2018.05.014
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发表时间：
2018-09
影响因子：
3.9
通讯作者：
Peter Guengerich F
中科院分区：
文献类型：
--
作者：
Albertolle ME;Peter Guengerich F
本文综述了细胞色素P450 （P450）与H2O2的关系。这种关联可以以三种不同的方式影响生物学。首先，p450在催化或无底物存在时产生H2O2作为副产物。这种反应被称为解偶联，释放出可能与疾病有关的活性氧。其次，在p450催化的过氧酶和过氧化物酶反应中，H2O2作为供氧共底物。这种活性已被证明主要在涉及原核生物p450的反应中起重要作用，研究人员已经利用这种反应适应工业用途。第三，我们的实验室已经研究了人类p450的h2o2依赖性抑制，证明了血红素的破坏以及血红素硫代酸配体氧化为亚磺酸（-SOH）的失活。p450的这种可逆氧化修饰可能具有防止解偶联的意义，并可能为这些酶的氧化调节提供新的见解。研究已经阐明了P450和H2O2之间关系的许多化学机制，但在生物学上的应用很难评价。需要进一步的研究来揭示活性氧在生物体环境中的有害和保护性质。
In this review we address the relationship between cytochromes P450 (P450) and H2O2. This association can affect biology in three distinct ways. First, P450s produce H2O2 as a byproduct either during catalysis or when no substrate is present. This reaction, known as uncoupling, releases reactive oxygen species that may have implications in disease. Second, H2O2 is used as an oxygen-donating co-substrate in peroxygenase and peroxidase reactions catalyzed by P450s. This activity has proven to be important mainly in reactions involving prokaryotic P450s, and investigators have harnessed this reaction with the aim of adaptation for industrial use. Third, H2O2-dependent inhibition of human P450s has been studied in our laboratory, demonstrating heme destruction and also the inactivating oxidation of the hemethiolate ligand to a sulfenic acid (-SOH). This reversible oxidative modification of P450s may have implications in the prevention of uncoupling and may give new insights into the oxidative regulation of these enzymes. Research has elucidated many of the chemical mechanisms involved in the relationship between P450 and H2O2, but the application to biology is difficult to evaluate. Further studies are needed reveal both the harmful and protective natures of reactive oxygen species in an organismal context.
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DOI：
10.1016/s0006-291x(77)80131-9
发表时间：
1977-01-01
影响因子：
3.1
作者：
EISENSTEIN, L;DEBEY, P;DOUZOU, P
通讯作者：
DOUZOU, P
影响因子：
3.2
作者：
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通讯作者：
Auclair, Karine
影响因子：
4.8
作者：
Bansal, Seema;Liu, Chuan-Peng;Avadhani, Narayan G.
通讯作者：
Avadhani, Narayan G.
影响因子：
4.8
作者：
Bansal, Seema;Anandatheerthavarada, Hindupur K.;Avadhani, Narayan G.
通讯作者：
Avadhani, Narayan G.
影响因子：
3.6
作者：
Dostalek, Miroslav;Brooks, Joshua D.;Guengerich, F. Peter
通讯作者：
Guengerich, F. Peter