Compound I of heme oxygenase cannot hydroxylate its heme meso-carbon.
Heme oxygenase (HO) catalyzes heme catabolism through three successive oxygenation steps where the substrate heme itself activates O2. It has been thought that the reactive species responsible for the first heme oxygenation, meso-hydroxylation, is the hydroperoxy-ferric heme intermediate (Fe-OOH) rather than an oxo ferryl porphyrin cation radical, so-called compound I. A recent theoretical study (Kamachi, T.; Yoshizawa, K. J. Am. Chem. Soc. 2005, 127, 10686), however, proposed that compound I can oxidize its meso-carbon atom with the assistance of a bridging water molecule. In this communication, we report the first direct observation of compound I of a heme-HO-1 complex, generated by reaction of ferric-HO-1 with m-chloroperbenzoic acid. HO compound I slowly decays to compound II without producing any meso-hydroxylated products. It does react with guaiacol and thioanisole, however. Our findings unambiguously rule out involvement of compound I in the HO catalysis.
Matsui
Toshitaka
T
Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Katahira, Sendai, Japan. mis2@tagen.tohoku.ac.jp
Kim
Sun Hee
SH
Jin
Hiromichi
H
Hoffman
Brian M
BM
Ikeda-Saito
Masao
M
D000818:Animals; D001665:Binding Sites; D002384:Catalysis; D002723:Chlorobenzoates / Q000737:chemistry / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D005290:Ferric Compounds / Q000737:chemistry / Q000378:metabolism; D006418:Heme / Q000737:chemistry* / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000737:chemistry* / Q000378:metabolism; D006900:Hydroxylation; D051381:Rats
D002723:Chlorobenzoates; D005290:Ferric Compounds; D006418:Heme; D051547:Heme Oxygenase-1; C000433:3-chloroperbenzoic acid