Models heme oxygenase

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

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

Although generalizations regarding the hematological effects of fuel oils on humans cannot be made, the effect of kerosene on the first two steps of the heme synthetic pathway has been studied in an animal model. Both hepatic -aminolevulinic acid ( -ALA) dehydratase and -ALA synthetase activities were decreased in female rats after intraperitoneal injection of kerosene, while heme oxygenase was unaffected (Rao and Pandya 1980). Since -ALA synthetase is the rate-limiting enzyme of the heme biosynthesis pathway, hepatic heme biosynthesis may be inhibited by kerosene. It is conceivable that this may be related to the extramedullary hematopoiesis reported in other studies (NTP/NIH 1986) however, there are no direct data to support this. 

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. 

Models of the low-spin iron(lll) hydroperoxide intermediate of heme oxygenase Magnetic resonance evidence for thermodynamic stabilization of the d(xy) electronic state at ambient temperatures. J. Am. Chem. Soc. 124, 6077-6089. 

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,... 

Rivera et have used variable temperature NMR hyperfine chemical shifts to probe the electron spin density in a low-spin Fe(III) porphyrinate that models the hydroperoxide intermediate (Felll-OOH) of heme oxygenase. Variable temperature NMR measurements, in conjunction with ENDOR, indicated that the ruffled (dxy) and planar (dxy) spin states are in thermal equilibrium. The authors suggest that this kind of spin-state equilibrium may be important for enzymatic function. The same group used NMR and pulsed ENDOR to characterize the electronic and spin states of C-labeled porphyrin models of the low-spin Fe(III) hydroperoxide intermediate of heme oxygenase. The ferric hydroperoxide intermediate in heme catabolism has also been studied by Caig-nan et using NMR. 

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