Heme oxygenase catalyzes the regiospecific oxidation of hemin to biliverdin IXα with concomitant liberation of CO and iron by three sequential monooxygenase reactions. The α-regioselectivity of heme oxygenase has been thought to result from the regioselective oxygenation of the heme α-meso position at the first step, which leads to the reaction pathway via meso-hydroxyheme IXα and verdoheme IXα intermediates. However, recent reports concerning heme oxygenase forming biliverdin isomers other than biliverdin IXα raise a question whether heme oxygenase can degrade meso-hydroxyhemin and isomers other than the α-isomers. In this paper, we investigated the stereoselectivity of each of the two reaction steps from meso-hydroxyhemin to verdoheme and verdoheme to biliverdin by using a truncated form of rat heme oxygenase-1 and the chemically synthesized four isomers of meso-hydroxyhemin and verdoheme. Heme oxygenase-1 converted all four isomers of meso-hydroxyhemin to the corresponding isomers of verdoheme. In contrast, only verdoheme IXα was converted to the corresponding biliverdin IXα. We conclude that the third step, but not the second, is stereoselective for the α-isomer substrate. The present findings on regioselectivities of the second and the third steps have been discussed on the basis of the oxygen activation mechanisms of these steps.
ASJC Scopus subject areas