Heme oxygenase model systems

Prior to the purification of heme oxygenase in sufficient quantities to carry out in vitro studies, the coupled oxidation of myoglobin was 

Although the coupled oxidation reaction closely resembles the enzymatic reaction, it may not be identical. One clear difference is that heme free in solution is oxidized at all four meso positions 40), heme in myoglobin only at the a-meso position 6, 46) and heme in hemoglobin at the a- and -positions 6, 46). Prior to the observation that hemin in 

The differences between the myoglobin model and heme oxygenase that account for the increased efficiency of heme cleavage by the latter 

---

Biological Function of Heme Oxygenase Heme Oxygenase Model Systems Heme Oxygenase The Protein... 

Despite detailed and repeated measurements by various techniques, almost no evidence can be found for the formation of (LFe=0) in the cyclidene systems, despite the fact that peroxo complexes form readily and by one route that constitutes the reverse of the reaction of equation 6. The results reported here also stand in contrast to recent studies based on non-heme oxygenase model systems that indicate the possibility of multiple pathways, implying that (hydroperoxo)iron(III) species might have catalytic activity e.g., a) Y.-D. Wu, K. N. Houk, J. S. Valentine, and W. Nam, Inorg, Chem, 31 718 (1992) b) W. Nam, R. Ho, and J. S. Valentine, J, Am,... 

A number of studies have examined the anti-inflammatory aetivities of CO (Abraham et al, 1988 Mannaioni et al, 2006). An activation of the heme oxygenase system and exposure to CO in vitro (Chauveau et al, 2005 Gibbons and Farrugia, 2004 Otterbein et al, 1999, 2000 Pae et al, 2004 Sethi et al, 2002) and in vivo (Dolinay et al, 2004 Nakao et al, 2003 Neto et al, 2004 Otterbein et al, 1999) revealed anti-inflainmatory activity in animal models but not in humans (Mayr et al, 2005). CO can inhibit apoptosis of endothelial cells (Soares et al, 2002). There is some evidence that upregulation of HO-1 might be beneficial in inflammatory diseases (Willis et al, 1996). In any case, the ability of CO to inhibit platelet aggregation and inflammation has important therapeutic implications and needs to be explored. 

Kutty G, Hayden B, Osawa Y, Wiggert B, Chader GJ, Kutty RK. Heme oxygenase expression in human retina and modulation by stress agents in human retinoblastoma cell model system. Curr Eye Res 1992 11 153-160. 

Formation of metal-oxo species first became realistic in model studies on heme oxygenases (shunt path), and it has also become popular in nonheme systems. As for the metal-jd-peroxo species, the distinctive example of model study has appeared in the copper enzymes. The type 7 peroxo species has been proposed first based on models for dicopper oxy-hemocyanin [19, 20] before demonstration of the same oxygen bonding in enzyme [13]. The type 7 x-peroxo structure has been applied to diiron species in sMMO [14] in addition to 6 [21]. (see Chapter 8)... 

The most notable reaction is that of metal-oxygen species with substrate. In the case of heme iron monooxygenases, high-valent iron-oxo species such as 3 or 4 in Fig. 5 are believed to react with substrates. On the other hand, both hydroperoxo (2) and 0x0 (3) are proposed for reactions by nonheme iron oxygenases. There are discussions on whether the iron-oxo species (3) is stabilized in the nonheme oxygenases in the absence of a porphyrin ligand which is effective to form 4. However, the iron-oxo species is attractive for explanation of the results obtained by monooxygenations by nonheme model iron systems. 

---