The O2 and CO reactions with the heme, α-hydroxy-heme, 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, K(O2) = 30-80 μM-1, which is 30-90-fold greater than those of mammalian myoglobins. The O2 association rate constants are similar to those for myoglobins (k(O2)/'= 7-20 μM-1 s- 1), whereas the O2 dissociation rates are remarkably slow (k(O2) = 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 α- hydroxyheme complex are similar to those of the protoheme complex, and hydroxylation at the α-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 (k(CO)/' ≃ 0.004 μM-1 s- 1) and a 300-fold greater dissociation rate constant (k(CO) ≃ 3 s-1) compared with the corresponding rate constants of the protoheme and α- hydroxyheme complexes. The positive charge on the verdoporphyrin ring causes a large decrease in reactivity of the iron.
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