Iron , in peroxidases

Figure 17 summarizes the compounds derived from peroxidase after Yamazaki and Yokota (36). The iron in peroxidase is trivalent and its... 

CH=CH2) are almost as efifective as protohemin in reactivating apoperoxidase but several other porphyrins do not reactivate at all (Fig. 24B). < Other metals cannot replace iron in peroxidase. 

The abihty of iron to exist in two stable oxidation states, ie, the ferrous, Fe ", and ferric, Fe ", states in aqueous solutions, is important to the role of iron as a biocatalyst (79) (see Iron compounds). Although the cytochromes of the electron-transport chain contain porphyrins like hemoglobin and myoglobin, the iron ions therein are involved in oxidation—reduction reactions (78). Catalase is a tetramer containing four atoms of iron peroxidase is a monomer having one atom of iron. The iron in these enzymes also undergoes oxidation and reduction (80). 

If step III in Scheme 6 is ignored, a simplification is reached that has been demonstrated to be reasonable with certain substrates (see below). As a consequence, then the 1 catalysts should oxidize targeted reductants in accordance with Eq. (13) (here [Fe-TAML] is the total concentration of all TAML iron in solution). Eq. (13) implies that the catalysis by 1 mimics the steady-state oxidation by peroxidase enzymes, where Compound I is much more reactive than Compound II (55). 

As in peroxidases, globins, and P450s, HO-1 has a helix over the distal surface of the heme (Figs. 16,18). In other heme proteins side chains from the distal helix provide the primary contacts with the heme as well as side chains that interact with heme ligands. In sharp contrast, the distal helix in HO-1 lies much closer to the heme such that backbone atoms form the primary heme contacts. In addition, there is no neighboring residue that could serve the same fimction as the distal His in the globins and peroxidases for interaction with iron-linked ligands. 

The heme iron in the peroxidase is oxidized by the peroxide from III+ to V4- in compound I. The compound I is reduced by two sequential one-electron transfer processes giving rise to the original enzyme. A substrate-free radical is in turn generated. This may have toxicological implications. Thus the myeloperoxidase in the bone marrow may catalyze the metabolic activation of phenol or other metabolites of benzene. This may underlie the toxicity of benzene to the bone marrow, which causes aplastic anemia (see below and chap. 6). The myeloperoxidase found in neutrophils and monocytes may be involved in the metabolism and activation of a number of drugs such as isoniazid, clozapine, procainamide, and hydralazine (see below). In in vitro systems, the products of the activation were found to be cytotoxic in vitro. 

Enzymes. Heme serves as the prosthetic group lor catalase, peroxidase, cytochrome oxidase, and the related cytochromes. Catalase and peroxidase iron are presumably present in the ferric form while the iron of Ihe cytochromes may exist in Ihe reduced or oxidized lorni. A number of tlasoproteins. including succinic dehydrogenase, contain iron in ihe molecule. Iron appears to act as coeiuyme for aeonilase. A number of other enzymes require the presence of iron for their activities,... 

---