O2- and H2O2-dependent verdoheme degradation by heme oxygenase: Reaction mechanisms and potential physiological roles of the dual pathway degradation

Toshitaka Matsui, Aya Nakajima, Hiroshi Fujii, Kathryn Mansfield Matera, Catharina T. Migita, Tadashi Yoshida, Masao Ikeda-Saito

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46 Citations (Scopus)


Heme oxygenase (HO) catalyzes the catabolism of heme to biliverdin, CO, and a free iron through three successive oxygenation steps. The third oxygenation, oxidative degradation of verdoheme to biliverdin, has been the least understood step despite its importance in regulating HO activity. We have examined in detail the degradation of a synthetic verdoheme IXα complexed with rat HO-1. Our findings include: 1) HO degrades verdoheme through a dual pathway using either O2 or H2O2; 2) the verdoheme reactivity with O2 is the lowest among the three O2 reactions in the HO catalysis, and the newly found H2O2 pathway is ∼40-fold faster than the O2-dependent verdoheme degradation; 3) both reactions are initiated by the binding of O2 or H2O2 to allow the first direct observation of degradation intermediates of verdoheme; and 4) Asp140 in HO-1 is critical for the verdoheme degradation regardless of the oxygen source. On the basis of these findings, we propose that the HO enzyme activates O2 and H 2O2 on the verdoheme iron with the aid of a nearby water molecule linked with Asp140. These mechanisms are similar to the well established mechanism of the first oxygenation, meso-hydroxylation of heme, and thus, HO can utilize a common architecture to promote the first and third oxygenation steps of the heme catabolism. In addition, our results infer the possible involvement of the H2O2-dependent verdoheme degradation in vivo, and potential roles of the dual pathway reaction of HO against oxidative stress are proposed.

Original languageEnglish
Pages (from-to)36833-36840
Number of pages8
JournalJournal of Biological Chemistry
Issue number44
Publication statusPublished - 2005 Nov 4

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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