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.
Highlights
We have examined the reactions of O2 and CO with the heme, ␣-hydroxyheme, and verdoheme complexes of heme oxygenase
The CO association reactions of both the Heme oxygenase (HO)-1 and HO-2 heme complexes are biphasic with the faster phase showing a bimolecular rate that is about 4ϳ5 times larger than that of the slower phase
The high O2 affinity of leghemoglobin is caused by a very large association rate constant that is determined by enhanced reactivity of the heme iron toward O2 [24]
Summary
(Received for publication, August 14, 1997, and in revised form, November 4, 1997). Catharina Taiko Migita‡, Kathryn Mansfield Matera§, and Masao Ikeda-Saito¶ From the Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-4970. Electron donation to the oxy form initiates the three-step conversion of oxyheme to the ferric iron-biliverdin complex through ␣-hydroxyheme and verdoheme intermediates (Scheme 1). The final step involves electron donation from the reductase to convert the ferric ironbiliverdin complex to ferrous iron and biliverdin [7] Heme participates both as a prosthetic group and as a substrate, a property unique to heme oxygenase [5, 7]. A low CO affinity was reported for verdoheme-myoglobin [20], but the affinity of verdoheme-HO for CO has not been determined To this end, we have examined the reactions of O2 and CO with the heme, ␣-hydroxyheme, and verdoheme complexes of heme oxygenase. The CO affinities of the heme and ␣-hydroxyheme complexes are very similar to those of mammalian myoglobins
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