Heme oxygenase (HO-1). Evidence for electrophilic oxygen addition to the porphyrin ring in the formation of alpha-meso-hydroxyheme.
Previous studies have established that reaction of the rat heme-heme oxygenase complex with H2O2 proceeds normally to give verdoheme, whereas reaction of the complex with meta-chloroperbenzoic acid yields a ferryl (FeIV = O) species and a protein radical but no verdoheme. The heme-heme oxygenase complex is shown here to react regiospecifically with ethyl hydroperoxide to give alpha-meso-ethoxyheme. Formation of this product exactly parallels the formation of alpha-meso-hydroxyheme in the normal reaction supported by cytochrome P450 reductase/NADPH or H2O2. These results rule out a nucleophilic mechanism for the alpha-meso-hydroxylation catalyzed by heme oxygenase and indicate that it involves electrophilic (or possibly radical) addition of the distal oxygen of iron-bound peroxide (FeIII-OOH) to the porphyrin ring.
Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco 94143-0446.
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A
Wilks
J
J
Torpey
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PR
Ortiz de Montellano
D006418:Heme / Q000737:chemistry*; D006419:Heme Oxygenase (Decyclizing) / Q000737:chemistry*; D006861:Hydrogen Peroxide / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D010100:Oxygen / Q000737:chemistry*; D011166:Porphyrins / Q000737:chemistry*
D011166:Porphyrins; D006418:Heme; D006861:Hydrogen Peroxide; D006419:Heme Oxygenase (Decyclizing); D010100:Oxygen