Stereoselectivity of each of the three steps of the heme oxygenase reaction: hemin to meso-hydroxyhemin, meso-hydroxyhemin to verdoheme, and verdoheme to biliverdin.
Heme oxygenase catalyzes the regiospecific oxidation of hemin to biliverdin IXalpha with concomitant liberation of CO and iron by three sequential monooxygenase reactions. The alpha-regioselectivity of heme oxygenase has been thought to result from the regioselective oxygenation of the heme alpha-meso position at the first step, which leads to the reaction pathway via meso-hydroxyheme IXalpha and verdoheme IXalpha intermediates. However, recent reports concerning heme oxygenase forming biliverdin isomers other than biliverdin IXalpha raise a question whether heme oxygenase can degrade meso-hydroxyhemin and isomers other than the alpha-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 IXalpha was converted to the corresponding biliverdin IXalpha. We conclude that the third step, but not the second, is stereoselective for the alpha-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.
Zhang
Xuhong
X
Department of Biochemistry, Yamagata University School of Medicine, Yamagata 990-9585, Japan.
Fujii
Hiroshi
H
Matera
Kathryn Mansfield
KM
Migita
Catharina Taiko
CT
Sun
Danyu
D
Sato
Michihiko
M
Ikeda-Saito
Masao
M
Yoshida
Tadashi
T
D000818:Animals; D001664:Biliverdine / Q000138:chemical synthesis / Q000378:metabolism*; D002248:Carbon Monoxide / Q000378:metabolism; D005296:Ferrous Compounds / Q000378:metabolism; D006418:Heme / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D006427:Hemin / Q000378:metabolism*; D006900:Hydroxylation; D010084:Oxidation-Reduction; D051381:Rats; D013053:Spectrophotometry / Q000379:methods; D013237:Stereoisomerism
D005296:Ferrous Compounds; C099547:verdoheme; D006418:Heme; D006427:Hemin; D002248:Carbon Monoxide; D006419:Heme Oxygenase (Decyclizing); D001664:Biliverdine