Electrochemical reduction of ferrous alpha-verdoheme in complex with heme oxygenase-1.
Electrochemical reduction of ferrous alpha-verdoheme in complex with heme oxygenase-1.
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亚铁 α-绿血红素与血红素加氧酶-1 复合物的电化学还原。
DOI：
10.1016/j.jinorgbio.2007.05.016
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发表时间：
2007
影响因子：
3.9
通讯作者：
Noguchi,Masato
中科院分区：
文献类型：
--
作者：
Sato,Hideaki;Higashimoto,Yuichiro;Sakamoto,Hiroshi;Sugishima,Masakazu;Takahashi,Kenichi;Palmer,Graham;Noguchi,Masato
血红素加氧酶（HO）反应由三个连续的氧化反应组成，即血红素到α-羟基血红素，α-羟基血红素到绿血红素，以及绿血红素到胆绿素-铁螯合物。其中，最不为人所知的步骤是将绿血红素转化为胆绿素-铁螯合物。对于亚铁绿血红素的氧卟啉环的裂解，已经提出了绿血红素π-中性基团的参与。为了探究 H2O 反应中的这一假设机制，我们在厌氧条件下对与大鼠 HO-1 复合的亚铁绿血红素进行了电化学还原。根据电化学光谱变化，发现亚铁绿血红素氧卟啉环的单电子还原的中点电位相对于正常氢电极（NHE）为-0.47±0.01V。由于该电位远低于 NADPH-细胞色素 P450 还原酶和 NADPH 两种黄素的电位，因此得出结论，亚铁绿血红素的氧卟啉环的单电子还原不太可能发生，并且 π 中性自由基的形成不可能是 H2O 降解绿血红素的第一步。相反，考虑另一种机制似乎更合理，其中 O2 与绿血红素的亚铁结合是绿血红素降解的第一步。
The heme oxygenase (HO) reaction consists of three successive oxygenation reactions, i.e. heme to α-hydroxyheme, α-hydroxyheme to verdoheme, and verdoheme to biliverdin–iron chelate. Of these, the least understood step is the conversion of verdoheme to biliverdin–iron chelate. For the cleavage of the oxaporphyrin ring of ferrous verdoheme, involvement of a verdoheme π-neutral radical has been proposed. To probe this hypothetical mechanism in the HO reaction, we performed electrochemical reduction of ferrous verdoheme complexed with rat HO-1 under anaerobic conditions. On the basis of the electrochemical spectral changes, the midpoint potential for the one-electron reduction of the oxaporphyrin ring of ferrous verdoheme was found to be −0.47±0.01V vs the normal hydrogen electrode (NHE). Because this potential is far lower than those of both flavins of NADPH-cytochrome P450 reductase, and of NADPH, it is concluded that the one-electron reduction of the oxaporphyrin ring of ferrous verdoheme is unlikely to occur and that the formation of the π-neutral radical cannot be the initial step in the degradation of verdoheme by HO. Rather, it appears more reasonable to consider an alternative mechanism in which binding of O2to the ferrous iron of verdoheme is the first step in the degradation of verdoheme.