The oxygen and carbon monoxide reactions of heme oxygenase

The O(2) 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 O(2) and CO binding properties. The O(2) affinities are very high, KO(2) = 30-80 mu M(-1), which is 30-90-fold greater than those of mammalian myoglobins, The O(2) association rate constants are similar to those for myoglobins (k(O2)', = 7-20 mu M(-1) s(-1)), whereas the O(2) dissociation rates are remarkably slow (k(O2) = 0.25 s(-1)), implying the presence of very favorable interactions between bound O(2) and protein residues in the heme pocket, The CO affinities estimated for both isoforms are only 1-6-fold higher than the corresponding O(2) 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 (k(CO)' approximate to 0.004 mu M(-1) s(-1)) and a 300-fold greater dissociation rate constant (k(CO) approximate to 3 s(-1)) compared with the corresponding rate constants of the protoheme and alpha-hydroxyheme complexes, positive charge on the verdoporphyrin ring causes a large decrease in reactivity of the iron.