Hemoproteins dioxygen

Jameson, G. B., Molinaro, F. S., Ibers, etal., Models for the active-site of oxygen-binding hemoproteins - dioxygen binding-properties and the structures of (2-methylimidazole)-meso-tetra (a,a,a,a-ortho-pivalamidophenyl)porphyrinatoiron(II)-ethanol and its dioxygen adduct. J. Am. Chem. Soc. 1980, 102, 3224-3237. 

Hemoglobin, nitrosyl-, 4, 1194 Hemoglobin, oxy-diamagnetism, 6,686 Hemoproteins, 4,259 dioxygen... 

A less common reactive species is the Fe peroxo anion expected from two-electron reduction of O2 at a hemoprotein iron atom (Fig. 14, structure A). Protonation of this intermediate would yield the Fe —OOH precursor (Fig. 14, structure B) of the ferryl species. However, it is now clear that the Fe peroxo anion can directly react as a nucleophile with highly electrophilic substrates such as aldehydes. Addition of the peroxo anion to the aldehyde, followed by homolytic scission of the dioxygen bond, is now accepted as the mechanism for the carbon-carbon bond cleavage reactions catalyzed by several cytochrome P450 enzymes, including aromatase, lanosterol 14-demethylase, and sterol 17-lyase (133). A similar nucleophilic addition of the Fe peroxo anion to a carbon-nitrogen double bond has been invoked in the mechanism of the nitric oxide synthases (133). 

Doyle, M. P., and Hoekstra, J. W. (1981). Oxidation of nitrogen oxides by bound dioxygen in hemoproteins. J. Inorg. Biochem. 14, 351-358. 

The situation for Fe11 porphyrin is rather similar, with the existence of 5 = 0, 1 and 2 states. The iron in Fe(TPP)(THF)2 lies in the plane of the porphyrin.647 This result is of considerable relevance to model systems for hemoglobin and the question of the trigger for the conformational change associated with the cooperative uptake of dioxygen. In this example the presence of a symmetrical weak axial field is the crucial factor. While this particular situation probably does not occur in any natural hemoprotein, these results demonstrate conclusively that high-spin Fe11 will fit into the porphyrin plane. 

Cytochrome P-450 is a hemoprotein that is distributed widely in nature in animal tissue and organelles, and in plants and microoganisms. Its main function lies in the monooxygenation of lipophilic substances, in which two electrons are taken up from NADPH with the reduction of one atom of dioxygen to water and insertion of the other into the substrate (equation 79). 

The symbiotic nitrogen-fixing system in root nodules contains the dioxygen-binding hemoprotein, leghemoglobin, but its function is still uncertain. 

Compared to knowledge of copper and nonheme iron-mediated processes (see Chapter 10), there is a great deal of information concerning the binding and activation of molecular dioxygen by hemoproteins and porphyrin-containing... 

The hydroxylation reaction is directly effected by an enzyme-hemoprotein, monooxigenase, cytochrome P450 containing protocheme IX. The reduction of the enzyme involves flavin reductases and electron carriers, such as adrenodoxin, rubredoxin, and cytochrome b5. Dioxygen, being a weak one-electron oxidant, is activated after the reduction in the enzyme heme coordination sphere. The various forms of cytochrome P450 from liver microsomes and from Pseudomonas putida have a molecular mass of about 49000. One of the subunits of the enzyme from mitochondria of... 

The reaction sequence at the heme active site starts with the binding of unactivated triplet dioxygen forming the so-called oxy-heme complexes. The iron center in 02-activating heme enz5maes is then thought to be converted into a peroxo anion species. It can be protonated to form a ferric hydroperoxo intermediate usually termed compormd 0 (183), which is a crucial reactive species in catalase and peroxidase enz5nne catalysis (Fig. 21). These hydroperoxo intermediates of hemoproteins are important... 

Fig. 21. Typical intermediates in hemoprotein enzyme active sites. The iron protoporphyrin IX cofactor (heme) forms dioxygen adducts termed oxy-species. In the course of oxygen activation and catalytic redox transformations, the oxy form can be consecutively converted into hydroperoxo- and oxo-type intermediates, which are usually referred to as compound 0, compound I, and compound II. Reproduced with permission from Ref (183). Copyright Nature Publishing Group.

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