Protoheme

Owrutsky J C, Li M, Locke B and Hochstrasser R M 1995 Vibrational relaxation of the CO stretch vibration in hemoglobin-CO, myoglobin-CO, and protoheme-CO J. Rhys. Chem. 99 4842-6... 

Peroxidases are found in milk and in leukocytes, platelets, and other tissues involved in eicosanoid metabolism (Chapter 23). The prosthetic group is protoheme. In the reaction catalyzed by peroxidase, hydrogen peroxide is reduced at the expense of several substances that will act as electron acceptors, such as ascorbate, quinones, and cytochrome c. The reaction catalyzed by peroxidase is complex, but the overall reaction is as follows ... 

Artifical photosynthetic reaction centers have continued to peak the interest of scientists over the years and this year is no exception. One such catenane-type example contains a ruthenium /m(2,2 -bipyridine) center, as the sensitizer, which is linked with cycloW.v(paraquat-p-phcnylenc), as the acceptor, and covalently linked with a protoheme or Zn-protoporphyrin, as the donor, located in the myoglobin pocket <00JA241>. A related assembly and on a Au-particle has appeared which possesses a Ru(II)-rm(2,2 -bipyridine)-... 

Figure 7.32 (A) Cytochrome c heme Fischer numbering system. (Adapted with permission from Figure 1 of reference 119b.) Copyright 2000 National Academy of Sciences, U.S.A.) (B) The protoheme IX numbering system as outlined in reference 112.

Peroxidases (E.C. 1.11.1.7) are ubiquitously found in plants, microorganisms and animals. They are either named after their sources, for example, horseradish peroxidase and lacto- or myeloperoxidase, or akin to their substrates, such as cytochrome c, chloro- or lignin peroxidases. Most of the peroxidases studied so far are heme enzymes with ferric protoporphyrin IX (protoheme) as the prosthetic group (Fig. 1). However, the active centers of some peroxidases also contain selenium (glutathione peroxidase) [7], vanadium (bromoperoxidase)... 

The heme of catalases is deeply buried within the core of the catalase subunit. Protoheme IX or heme b is found in all small-subunit catalases so far characterized. The two large-subunit enzymes HPII and PVC have been characterized biochemically, spectrally, and structurally 91) as containing heme d in which ring HI is oxidized to a cis-hydroxyspirolactone. Heme b is initially bound to both enzymes during assembly, and it is subsequently oxidized by the catalase itself during the early rounds of catalysis 92). 

The biphasic reaction with CO points to the existence of multiple heme-hemopexin conformers, and this is borne out by spectral analyses. The absorbance spectra of rabbit ferri-, ferro-, and CO-ferro-mesoheme-hemopexin are entirely analogous to those of other bis-histidyl heme proteins such as cytochrome 65 142), but the CD spectra exhibit unusual features (Fig. 11). Of particular interest are the weak signal of the ferro complex and the bisignate signal of the CO-ferro complex (also seen in the NO-ferro-mesoheme-hemopexin complex (140) and in human ferri-protoheme—hemopexin (139)). 

However, this explanation is not sufficient to accoimt for the bipha-sic CD spectrum of human ferri-protoheme—hemopexin (with 2,4-vinyl substituents), as well as the much weaker human CO-ferro-heme-hemopexin bisignate signal compared to the rabbit congener (139), and hence other factors must be involved. Several potential effectors exist (a) exciton coupling (b) the conformers produced by a 180° rotation about the a- and y-meso-carbon axis and consequent nonisometric interactions of the as5unmetric 2,4- and 9,10-substituents (c) the aromatic tryptophan residues near the heme binding site (s) and (d) two independent binding modes or sites. 

Since C has been assigned to a triplet deoxy state in which the axial ligand has been dissociated. As can be seen in Table 111, in most cases lifetimes are found to compare favorably between the carbon monoxide and oxygen forms of the synthetic complexes. In all cases the rate constants used had an accuracy of only one significant figure, resulting in an accuracy no better for the lifetimes or these states. One noticeable discrepancy in occurs between the chelated protoheme 1 -CO and the oxygen form of this compound, i 02. 

The work of Gadher et al and the awareness of the diversity of the biological activity of FBI fungicides suggests that the structure of the fungitoxicant must satisfy more than one requirement. The ability to bind to the protoheme iron of cytochrome P-450 appears to be a required function for activity. The fitness to bind could be dependent upon several facets such as ... 

This enzyme [EC 4.99.1.1], also known as protoheme ferro-lyase and heme synthetase, catalyzes the reaction of protoporphyrin with Fe(II) to yield protoheme and two protons. 

This FMN- and protoheme IX-dependent enzyme [EC 1.1.2.3] catalyzes the reaction of (5)-lactate with two ferricytochrome c to produce pyruvate and two ferrocy-tochrome c. 

Peroxidases (EC 1.11.1.7), which have ferric protoheme prosthetic groups, react non-selectively via free radical mechanisms, using hydrogen peroxide as the electron acceptor. A reactive Fe(IV)-0 species and a radical heme intermediate are formed, and the intermediate then reacts with the reducing substrate to produce the oxidized product, regenerating the Fe(III) ion. 

The ferrous complex of octaethyl porphyrin in SDS micelles has been characterized as four coordinated (S = 1) ferrous heme species and is similar to that observed for the ferrous protoheme complex in CTAB. It is noted that ferrous complexes of natural porphyrins cannot be stabilized in aqueous SDS micelles, and much larger aqueous micelles like CTAB were needed to stabilize various ferrous protohemes. This indicates that the environment around the octaethyl porphyrin complex in aqueous SDS is more hydrophobic than that of the analogous natural heme species, suggesting that the OEP moiety is embedded much deeper inside the micellar hydrophobic cavity than the protoporphyrin analogue. 

---