Stereoselectivity of Each of the Three Steps of the Heme Oxygenase Reaction: Hemin to meso-Hydroxyhemin, meso-Hydroxyhemin to Verdoheme, and Verdoheme to Biliverdin
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- 作者：Xuhong Zhang ; Hiroshi Fujii ; Kathryn Mansfield Matera ; Catharina Taiko Migita ; Danyu Sun ; Michihiko Sato ; Masao Ikeda-Saito ; and Tadashi Yoshida
- 刊名：Biochemistry
- 出版年：2003
- 出版时间：June 24, 2003
- 年：2003
- 卷：42
- 期：24
- 页码：7418 - 7426
- 全文大小：207K
- 年卷期：v.42,no.24(June 24, 2003)
- ISSN：1520-4995
文摘
Heme oxygenase catalyzes the regiospecific oxidation of hemin to biliverdin IX
withconcomitant liberation of CO and iron by three sequential monooxygenase reactions. The -regioselectivityof heme oxygenase has been thought to result from the regioselective oxygenation of the heme -mesoposition at the first step, which leads to the reaction pathway via meso-hydroxyheme IX and verdohemeIX intermediates. However, recent reports concerning heme oxygenase forming biliverdin isomers otherthan biliverdin IX raise a question whether heme oxygenase can degrade meso-hydroxyhemin and isomersother than the -isomers. In this paper, we investigated the stereoselectivity of each of the two reactionsteps from meso-hydroxyhemin to verdoheme and verdoheme to biliverdin by using a truncated form ofrat heme oxygenase-1 and the chemically synthesized four isomers of meso-hydroxyhemin and verdoheme.Heme oxygenase-1 converted all four isomers of meso-hydroxyhemin to the corresponding isomers ofverdoheme. In contrast, only verdoheme IX was converted to the corresponding biliverdin IX. Weconclude that the third step, but not the second, is stereoselective for the -isomer substrate. The presentfindings on regioselectivities of the second and the third steps have been discussed on the basis of theoxygen activation mechanisms of these steps.
withconcomitant liberation of CO and iron by three sequential monooxygenase reactions. The -regioselectivityof heme oxygenase has been thought to result from the regioselective oxygenation of the heme -mesoposition at the first step, which leads to the reaction pathway via meso-hydroxyheme IX and verdohemeIX intermediates. However, recent reports concerning heme oxygenase forming biliverdin isomers otherthan biliverdin IX raise a question whether heme oxygenase can degrade meso-hydroxyhemin and isomersother than the -isomers. In this paper, we investigated the stereoselectivity of each of the two reactionsteps from meso-hydroxyhemin to verdoheme and verdoheme to biliverdin by using a truncated form ofrat heme oxygenase-1 and the chemically synthesized four isomers of meso-hydroxyhemin and verdoheme.Heme oxygenase-1 converted all four isomers of meso-hydroxyhemin to the corresponding isomers ofverdoheme. In contrast, only verdoheme IX was converted to the corresponding biliverdin IX. Weconclude that the third step, but not the second, is stereoselective for the -isomer substrate. The presentfindings on regioselectivities of the second and the third steps have been discussed on the basis of theoxygen activation mechanisms of these steps.