title: The oxygen and carbon monoxide reactions of heme oxygenase.
abstract: The O2 and CO reactions with the heme, alpha-hydroxyheme, and verdoheme complexes of heme oxygenase have been studied. The heme complexes of heme oxygenase isoforms-1 and -2 have similar O2 and CO binding properties. The O2 affinities are very high, KO2 = 30-80 microM-1, which is 30-90-fold greater than those of mammalian myoglobins. The O2 association rate constants are similar to those for myoglobins (kO2' = 7-20 microM-1 s-1), whereas the O2 dissociation rates are remarkably slow (kO2 = 0.25 s-1), implying the presence of very favorable interactions between bound O2 and protein residues in the heme pocket. The CO affinities estimated for both isoforms are only 1-6-fold higher than the corresponding O2 affinities. Thus, heme oxygenase discriminates much more strongly against CO binding than either myoglobin or hemoglobin. The CO binding reactions with the ferrous alpha-hydroxyheme complex are similar to those of the protoheme complex, and hydroxylation at the alpha-meso position does not appear to affect the reactivity of the iron atom. In contrast, the CO affinities of the verdoheme complexes are >10,000 times weaker than those of the heme complexes because of a 100-fold slower association rate constant (kCO' approximately 0. 004 microM-1 s-1) and a 300-fold greater dissociation rate constant (kCO approximately 3 s-1) compared with the corresponding rate constants of the protoheme and alpha-hydroxyheme complexes. The positive charge on the verdoporphyrin ring causes a large decrease in reactivity of the iron.
authors.affiliation: Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-4970, USA.
authors.forename: C T
authors.initials: CT
authors.lastname: Migita
authors.forename: K M
authors.initials: KM
authors.lastname: Matera
authors.forename: M
authors.initials: M
authors.lastname: Ikeda-Saito
authors.forename: J S
authors.initials: JS
authors.lastname: Olson
authors.forename: H
authors.initials: H
authors.lastname: Fujii
authors.forename: T
authors.initials: T
authors.lastname: Yoshimura
authors.forename: H
authors.initials: H
authors.lastname: Zhou
authors.forename: T
authors.initials: T
authors.lastname: Yoshida
mesh_terms: D000818:Animals; D002248:Carbon Monoxide / Q000378:metabolism*; D002384:Catalysis; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D006427:Hemin / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D011994:Recombinant Proteins; D006427:Hemin; D002248:Carbon Monoxide; D006419:Heme Oxygenase (Decyclizing); D010100:Oxygen