Heme Oxygenase Activity Current Methods and Applications

  • Stefan W. Ryter
  • Egil Kvam
  • Rex M. Tyrrell
Part of the Methods in Molecular Biology™ book series (MIMB, volume 99)

Abstract

The heme oxygenase enzymes (HO-1 and HO-2) oxidize heme to biliver-din-IXα (BVIXα), releasing carbon monoxide (CO) and iron (Fig. 1). HO enzymes control the rate of heme degradation and, consequently, also control the redistribution of the heme iron (1). The CO generated from the HO reaction affects signal transduction pathways in neuronal and vascular systems (2).
Fig. 1.

The pathway of heme metabolism. Heme oxygenase (HO-1), first described as a microsomal mixed-function oxygenase (E.C. 1:14:99:3, heme-hydrogen donor:oxygen oxidoreductase), catalyzes the rate-determining step in heme metabolism. Both heme oxygenase isozymes (HO-1 and HO-2) oxidize heme (ferriprotoporphyrin IX) to the bile pigment biliverdin-IXa, in a reaction requiring 3 mol of molecular oxygen. The accessory enzyme, NADPH:cytochrome p-450 reductase, reduces the ferric heme iron as a prerequisite for each cycle of oxygen binding and (continued) oxygen activation. The cleavage of the heme ring frees the coordinated iron, as well as the α-methene bridge carbon as carbon monoxide. The principle HO reaction product, biliverdin-IXα, is further metabolized by divalent reduction to form bilirubin-IXα, by NAD(P)H:biliverdin reductase. Heme side chains are designated as M, methyl; V, vinyl; and P, propionate.

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Copyright information

© Humana Press Inc., Totowa, NJ 2000

Authors and Affiliations

  • Stefan W. Ryter
    • 1
  • Egil Kvam
    • 2
  • Rex M. Tyrrell
    • 2
  1. 1.Division of Endocrinology, Metabolism, and Molecular Medicine, Department of Internal MedicineSouthern Illinois University School of MedicineSpringfield
  2. 2.Department of Pharmacy and PharmacologyUniversity of BathBath

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