Stereoselectivity of each of the three steps of the heme oxygenase reaction: hemin to meso-hydroxyhemin, meso-hydroxyhemin to verdoheme, and verdoheme to biliverdin.
Stereoselectivity of each of the three steps of the heme oxygenase reaction: hemin to meso-hydroxyhemin, meso-hydroxyhemin to verdoheme, and verdoheme to biliverdin.
复制标题
血红素加氧酶反应三个步骤中每一步的立体选择性：血红素到内消旋羟基血红素、内消旋羟基血红素到绿血红素、以及绿血红素到胆绿素。
DOI：
10.1021/bi027173g
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发表时间：
2003
期刊：
影响因子：
2.9
通讯作者：
Yoshida,Tadashi
中科院分区：
文献类型：
--
作者：
Zhang,Xuhong;Fujii,Hiroshi;Matera,KathrynMansfield;Migita,CatharinaTaiko;Sun,Danyu;Sato,Michihiko;Ikeda-Saito,Masao;Yoshida,Tadashi
血红素加氧酶催化区域特异性的氯化血红素氧化成胆绿素IXα，同时通过三个连续的单加氧酶反应释放CO和铁。血红素加氧酶的α区域选择性被认为是第一步血红素α中位位区域选择性氧化的结果，该反应途径是通过O-羟基血红素IXα和Verdoheme IXα中间产物。然而，最近关于血红素加氧酶形成胆绿素异构体而不是胆绿素IXα的报道提出了一个问题，即血红素加氧酶是否能降解脱氢氯化血红素和α异构体以外的异构体。本文利用一种截断的大鼠血红素加氧酶-1和化学合成的四种异构体，研究了从中羟基氯化高铁血红素到马鞭铁血红素和马鞭铁血红素到胆绿素两个反应步骤的立体选择性。血红素加氧酶-1将中羟基氯化血红素的所有四种异构体转化为相应的马鞭铁血红素异构体。相反，只有Verdoheme IXα被转化为相应的胆绿素IXα。我们得出结论，对于α-异构体底物来说，第三步是立体选择性的，而不是第二步。根据第二步和第三步的氧活化机理，讨论了目前关于这些步骤的区域选择性的研究结果。
Heme oxygenase catalyzes the regiospecific oxidation of hemin to biliverdin IXα with concomitant liberation of CO and iron by three sequential monooxygenase reactions. The α-regioselectivity of heme oxygenase has been thought to result from the regioselective oxygenation of the heme α-mesoposition at the first step, which leads to the reaction pathway viameso-hydroxyheme IXα and verdoheme IXα intermediates. However, recent reports concerning heme oxygenase forming biliverdin isomers other than biliverdin IXα raise a question whether heme oxygenase can degrademeso-hydroxyhemin and isomers other than the α-isomers. In this paper, we investigated the stereoselectivity of each of the two reaction steps frommeso-hydroxyhemin to verdoheme and verdoheme to biliverdin by using a truncated form of rat heme oxygenase-1 and the chemically synthesized four isomers ofmeso-hydroxyhemin and verdoheme. Heme oxygenase-1 converted all four isomers ofmeso-hydroxyhemin to the corresponding isomers of verdoheme. In contrast, only verdoheme IXα was converted to the corresponding biliverdin IXα. We conclude that the third step, but not the second, is stereoselective for the α-isomer substrate. The present findings on regioselectivities of the second and the third steps have been discussed on the basis of the oxygen activation mechanisms of these steps.