Hemoglobin oxygenase

Hemoglobin oxygenase Guinea pig Hemoglobin Not identified Nakajima (1958) ... 

Fig. 1. Overview of intravascular heme catabolism. Hemoglobin, myoglobin, and other heme proteins are released into the circulation upon cellular destruction, and the heme moiety is oxidized by O2 to the ferric form (e.g., methemoglobin and metmyoglobin). Haptoglobin can bind a substantial amount of hemoglobin, but is readily depleted. Ferric heme dissociates from globin and can be bound by albumin or more avidly by hemopexin. Hemopexin removes heme from the circulation by a receptor-mediated transport mechanism, and once inside the ceU heme is transported to heme oxygenase for catabolism.

The first step in the two-step pathway, catalyzed by heme oxygenase (HO), converts heme to biliverdin, a linear (open) tetrapyrrole derivative (Fig. 22-25). The other products of the reaction are free Fe2+ and CO. The Fe2+ is quickly bound by ferritin. Carbon monoxide is a poison that binds to hemoglobin (see Box 5-1), and the production of CO by heme oxygenase ensures that, even in the absence of environmental exposure, about 1% of an individual s heme is complexed with CO. 

These superoxo complexes are relevant models for the naturally occurring oxygen carriers hemoglobin and myoglobin, which contain ferroprotoporphyrin IX as an active center in which the sixth axial postion is occupied by the imidazole moiety of histidine.17 They also intervene as primary oxygen adducts in enzymatic cytochrome P-450 oxygenases.18... 

A large number of investigations of the mechanism of electron transfer reactions of macromolecule-metal complexes in biological systems has been reported. These investigations were concerned with not only natural metalloenzymes such as cytochromes, ferredoxin, blue coppers, oxygenase, peroxidase, catalase, hemoglobin, and ruberodoxin, but also modified metalloenzymes 47). 

Oshiro S, Takeuchi H, Matsumoto M, Kurata S (1999) Transcriptional activation of heme oxygenase-1 gene in mouse spleen, fiver and kidney cells after treatment with lipopolysaccharide or hemoglobin. Cell Biol Int 23 465-474... 

At the same time there are differences between CO and NO. For example, NO is an unstable gas and radical while CO is a stable gas and not a radical. CO binds only ferrous heme but NO binds to both ferrous and ferric hemoprotein (Hartsfield, 2002). The combination rate of NO with hemoglobin is faster and dissociation slower than that of CO (Sharma and Ranney, 1978) so that the affinity of NO for hemoglobin is 1,500 times that of CO (Foresti and Motterlini, 1999). Formation of endogenous CO in a variety of tissues has been demonstrated (Marks et al, 2002). Given the complexity of colocalization and activities of heme oxygenase and nitric oxide synthase, it has been speculated that CO and NO could function in a synergistic, compensatory, and/or counterregulatory way (Hartsfield, 2002). 

Tenhunen, R., Marver, H.S., Schmid, R. (1970). The enzymatic catabolism of hemoglobin stimulation of microsomal heme oxygenase by hemin. J. Lab. Clin. Med. 75 410-21. 

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