Hydrogen peroxide-heme group reaction

A quite different approach came from Chance and others using heme enzymes (1947). Purified horseradish peroxidase has a characteristic absorption spectrum which was visibly altered in the presence of hydrogen peroxide. When an appropriate substrate was added it was oxidized by the hydrogen peroxide and the spectrum reverted to that of the original state of the enzyme. Similar studies were performed with catalase, showing that prosthetic groups in enzymes underwent reversible changes in the course of their reactions. 

This enzyme [EC 1.11.1.10], also called chloride peroxidase, catalyzes the reaction of hydrogen peroxide with two RH and two Cl to produce two R—Cl and two water molecules. A heme group is one of the cofactors. This enzyme can also catalyze bromination and iodin-ation, but not fluorination. 

Kinetic studies have shown that the product formed in the reaction of the fully oxidized enzyme with hydrogen peroxide is catalytically inactive. Reaction of the half-reduced enzyme with hydrogen peroxide leads to an enzymatically active compound, in which the Fe" heme is oxidized to Fe, and the FeIU heme is oxidized to the FeIV ferryl species. No stoichiometric formation of a radical species is observed, unlike the case for other peroxidases. The peroxide-oxidized enzyme will then oxidize two molecules of reduced cytochrome c. Mechanistic details are still unclear, particularly with regard to the interaction between the two heme groups, a phenomenon revealed by ESR studies.1373... 

It is shown that with the model system [38, 59] heme iron reaction with hydrogen peroxide is promoted by acidic catalytic sites, which are replaced by distal amino acid group bound to heme [60], Here experimentally observed two-electron oxidation substrate in one stage and corresponded hydride-ion transfer is confirmed [61, 62], In the example of catalase reaction the transfer mechanism of two electrons simultaneously was discussed above... 

Other heme compounds are also active biochemically. Cytochrome P-450 catalyzes oxidation reactions in the liver and adrenal cortex, helping to detoxify some substances by adding hydroxyl groups that make the compounds more water-soluble and more susceptible to further reactions. Unfortunately, at times this process has the reverse effect because some relatively safe molecules ai-e converted into potent carcinogens. Peroxidases and catalases are Fe(III)-heme compounds that decompose hydrogen peroxide and organic peroxides. The reactions seem to proceed through Fe(IV) compounds with another unpaired electron on the porphyrin, which becomes a radical cation. Similar intermediates are also known in simpler porphyrin molecules. ... 

Hydrogen peroxide is a substrate for myeloperoxidase, a multisubunit heme protein of M.W. 150,C, present in primary neutrophilic granules. The active prosthetic groups are two hemes covalently attached to the apoen-zyme. This enzyme catalyzes many kinds of oxidation reactions, but oxidation of halide ions to hypohalite ions appears to be the most important. Hypochlorite ion is the principal compound formed, although Br , I, and SCN (a pseudohalide) can also serve as substrates. The reaction catalyzed is... 

---