Hemoproteins compounds

Hemoproteins, such as hemoglobin and the cytochromes, contain heme. Heme is an iron-porphyrin compound (Fe -protoporphyrin IX) in... 

Until very recently no complexes of Fe + were known, and so we examined the electronic ground state of these highly oxidized hemoproteins, which are known as the compound I derivatives,... 

A comparison of porphyrin and pincer activity rationalized through reactivity index Porphyrin and pincer complexes are both important categories of compounds in biological and catalytic systems. Structure, spectroscopy, and reactivity properties of porphyrin pincers are systematically studied for selection of divalent metal ions. It is reported that the porphyrin pincers are structurally and spectroscopically different from their precursors and are more reactive in electrophilic and nucleophilic reactions. These results are implicative in chemical modification of hemoproteins and understanding the chemical reactivity in heme-containing and other biologically important complexes and cofactors [45]. 

Up to now, two types of iron compounds have been studied with ENDOR, namely heme compounds (hemoproteins and some heme model compounds) and iron-sulfur proteins. For comprehensive summaries of the corresponding EPR work, the reader is referred to the literature234-2371. 

Much work has demonstrated the presence of complex multienzyme monooxygenase systems within the endoplasmic reticulum of several mammalian species (for Reviews 1, 2, 3). These monooxygenase systems are responsible for the oxidative metabolism of many exogenous and endogenous substances, and the unusual non-specificity of these monooxygenase enzymes allows the metabolism of compounds with diverse chemical structures. Early work demonstrated that the terminal microsomal oxidase involved in xenobio-tic biotransformation was a hemoprotein, which has been subsequently named cytochrome P-450. 

The enzyme horseradish peroxidase is a hemoprotein and the region of the Soret band exhibits large differences between the position and extinction coefficients of the uncombined and combined forms. Both forms were first studied by spectrophotometry, but the E—S complexes were 0 labile that they could not be examined extensively by any other spectroscopic method. Using rapid-scanning spectrophotometry and rapid mixing, Chance was able to distinguish the spectra of compound I and II and determine the various rate constants of the multistep reaction with rather poor precision. 

The donor type D5 comprises the two species azide and hydroxy-lamine. These both react with the enz5mie in the presence of peroxide to give rise to ferrous forms of catalase, otherwise normally inaccessible (catalase is the only common hemoprotein that is nonreducible by dithionite). The final inhibited form of catalase in the presence of azide and peroxide is NO-ferrocatalase, but not every azide molecule becomes an NO only in the presence of CO is there a stoichiometric inhibition of enzyme by peroxide with formation of 1 equiv of CO-ferrocatalase for every peroxide molecule added (43). This suggested a three-electron reduction of compound I either to give ferrocatalase, N2, and NO (10-20% total) or to give ferrocatalase, N, and N2O (80-90% total). However, Kalyanaraman et al. (45) have demonstrated the formation of the azidyl (N=N=N ) radical in the reaction, and Lardinois... 

Type II substrates are compounds such as nitrogenous bases, with sp2 or sp3 nonbonded electrons. These bind to iron and give rise to a 6-coordinated, low-spin hemoprotein. Such compounds may also be inhibitors of cytochromes P-450. The spectrum shows a peak at 420 to 435 nm and a trough at 390 to 410 nm in the difference spectrum. 

Isocyanides have been used to probe the bonding sites in hemoproteins and related compounds (215-219). Additions of CNCH2Ph, PBu , and P(OEt)3 to Fe(II)cap (cap = dianion of capped porphyrine) has produced five-coordinate low-spin iron(II) compounds by jr-acid destabilization of the dz2 orbital of the iron(II) porphyrin (215). 

Iron atoms in states other than Fe(II) and Fe(III) are rare in biological material, but there is one case where Mossbauer evidence has pointed to an Fe(IV) electronic configuration. Horseradish peroxidase, when it forms peroxide derivatives (Compounds I and II of HRP), displays an isomer shift which is about equal to that obtained with Fe metal (23). A similar observation has also been found on an analogous compound, Japanese Radish Peroxidase (72). There is no evidence for Fe(I) or Fe (IV) states in any other hemoproteins, or in any of the iron-sulfur proteins. 

The hyperfine shifts in the proton NMR spectra of paramagnetic hemes and hemoproteins are closely related to the electronic structures of these molecules. At present the most extensive NMR studies of the electronic spin distribution in the heme groups have been done with low spin ferric compounds, which will be discussed in this section. Procedures similar to those described here would apply to the analysis of the NMR spectra of hemoproteins in the other paramagnetic states (Table 1). 

Theoeretical models proposed by Griffith (36, 38) and Kotani (59, 60) are now generally employed for the interpretation of the spectral and magnetic properties of hemoproteins. In his recent review Weissbluth (106) gave a detailed account of the calculations involved in these models. The present discussion is limited to a brief outline of the treatment of low spin ferric heme compounds, and the presentation of some results which will be useful for the analysis of the NMR data. 

A more detailed treatment, including the effects of spin delocalization on the pseudocontact shifts, might be warranted once single crystal EPR data will become available for several of the low spin ferric heme compounds. In the hemoproteins it would then be of special interest to investigate pseudocontact shifts for amino acid residues near the heme groups which could yield structural information in a similar way as the ring current shifts. 

The peroxidase activity of PGHS is comparable to that of better known peroxidases such as horseradish peroxidase (HRP). The catalytic cycle of HRP is shown in Figure 5 [9], Its first step is the formation of an intermediate very often found in hemoproteins by transfer of an oxygen atom from various oxygen atom donors to the Fe(III) heme (Eq. 6). It is a high-valent iron-oxo species, at least formally a Fe(V)=0 complex. In fact, the detailed electronic structure of this intermediate depends on the environment of the heme provided by the protein. In HRP, this intermediate (called compound I) is a (porphyrin radical-cation)-Fe(IV)=0 complex, as shown by many spectroscopic techniques [9],... 

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