Heme proteins ferric forms

How does nature prevent the release of hydrogen peroxide during the cytochrome oxidase-mediated four-electron reduction of dioxygen It would appear that cytochrome oxidase behaves in the same manner as other heme proteins which utilize hydrogen peroxide, such as catalase and peroxidase (vide infra), in that once a ferric peroxide complex is formed the oxygen-oxygen bond is broken with the release of water and the formation of an oxo iron(IV) complex which is subsequently reduced to the ferrous aquo state (12). Indeed, this same sequence of events accounts for the means by which oxygen is activated by cytochromes P-450. 

Heme proteins in their various forms contain mainly the ferrous or ferric porphyrin moieties [6—77] (R some organic side chain of the protein A a small molecule act-ingas a-donor-TT-acceptor ligand, e.g., CO, 02, NO, CH3CN, CH3NC) (7, 20-34). In fact the binding of dioxygen to the pentacoordinate species [6] and [7] — an essential... 

In vivo heme is released into the plasma by erythrocyte lysis in the form of hemoglobin and by tissue trauma in the form of myoglobin, and both heme proteins are quickly oxidized to their ferric heme forms (methemoglobin and metmyoglobin) at the oxygen tension found in tissue capillary beds. 

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 three-dimensional structure of a protein determined was the dioxygen transporter myoglobin isolated from sperm whale in the ferric form (86, 87). A 153 amino acid globular protein, myoglobin contains eight helical regions (A to H) with a single heme b bound between helices... 

Electronic absorption maxima for LIP, MnP, horseradish peroxidase (HRP) and various llganded forms of these enzymes are shown in Table I. The spectra of native LIP and MnP are characteristic of high-spin ferric heme proteins, with Soret and visible maxima ( 407, 502 and... 

E° = —196 mV) to the ferric P450CAM heme iron to produce the ferrous state of the protein, 3. Dioxygen binds to the ferrous heme iron to form the ferrous oxy complex, 4a/4b, whose valence structure can be presented either as the ferrous-02, 4a, or as the ferric superoxide, 4b, complex. Addition of carbon monoxide to 3 yields a ferrous carbon monoxide adduct, 5, with its characteristic absorbance peak at 450 nm [37],... 

Both catalase and ascorbate peroxidase are heme-containing proteins with peroxidase activities. The mechanism by which SA inhibits the activity of both these enzymes appears to be similar [112]. The native ferric form of catalase (Fe III) undergoes a two electron... 

Thus, when intracellular levels of heme rise to a certain level, either by diffusion of free heme or from hemopexin-mediated transport, oxidation of proteins takes place. Free heme reportedly does not diminish GSH levels [119]. Thus, it would appear that a redox-active metal is involved. These cells are replete in ferritin and ferritin is induced as iron is released from heme catabolism. The form of metal, likely to be either Fe /Fe " ", Cu +/Cu +, Fe +-heme/Fe +-heme, is currently unknown as are the molecular sites of oxidation. Studies with ferrous and ferric che-... 

Figure 9. Crystal parameters for ferric lotu-spm forms of various heme proteins...

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