Peroxidases prosthetic group

Enzymes often need for their activity the presence of a non-protein portion, which may be closely combined with the protein, in which case it is called a prosthetic group, or more loosely associated, in which case it is a coenzyme. Certain metals may be combined with the enzyme such as copper in ascorbic oxidase and selenium in glutathione peroxidase. Often the presence of other metals in solution, such as magnesium, are necessary for the action of particular enzymes. 

In order for the cyclooxygenase to function, a source of hydroperoxide (R—O—O—H) appears to be required. The hydroperoxide oxidizes a heme prosthetic group at the peroxidase active site of PGH synthase. This in turn leads to the oxidation of a tyrosine residue producing a tyrosine radical which is apparendy involved in the abstraction of the 13-pro-(5)-hydrogen of AA (25). The cyclooxygenase is inactivated during catalysis by the nonproductive breakdown of an active enzyme intermediate. This suicide inactivation occurs, on average, every 1400 catalytic turnovers. 

Heme (C34H3204N4Fe) represents an iron-porphyrin complex that has a protoporphyrin nucleus. Many important proteins contain heme as a prosthetic group. Hemoglobin is the quantitatively most important hemoprotein. Others are cytochromes (present in the mitochondria and the endoplasmic reticulum), catalase and peroxidase (that react with hydrogen peroxide), soluble guanylyl cyclase (that converts guanosine triphosphate, GTP, to the signaling molecule 3, 5 -cyclic GMP) and NO synthases. 

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 ... 

The class II secreted fungal heme peroxidases include the LMPs LiP, MnP and VP [70]. All of these enzymes are extracellular and contain protoporphyrin IX (heme) as prosthetic group. They use H2O2 or organic hydroperoxides as electron accepting cosubstrates during the oxidation of diverse compounds. They are secreted as glycosilated, 35-38 kDa size proteins. 

It has the heme prosthetic group covalently bonded to protein cytochrome c does not lose its heme catalytic group in these systems, while peroxidases do (catalysis in organic solvents)... 

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. 

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 diversity among catalases, evident in the variety of subunit sizes, the number of quaternary structures, the different heme prosthetic groups, and the variety of sequence groups, enables them to be organized in four main groups the classic monofunctional enzymes (type A), the catalase-peroxidases (type B), the nonheme catalases (type C), and miscellaneous proteins with minor catalatic activities (type D). 

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. 

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,... 

As mentioned above, a prosthetic group of Mb, heme b, is the same as that of some heme peroxides such as HRP and CcP, and there are two characteristic histidines, the proximal and distal, in the heme pocket. However, the peroxidase and peroxygenase activities of Mb are much lower than those observed for the native heme peroxidase, which were discussed in Section V. In addition, Mb has... 

Peroxidases are enzymes catalysing the oxidation of a variety of organic and inorganic compounds by hydrogen peroxide or related compounds. An extensive list of the sources of peroxidase in plants and animals has been given (Saunders et al., 1964). All of the peroxidases purified so far from plants contain the prosthetic group hemin or ferriprotoporphyrin IX, 3 (Dunford and Stillman, 1976 Hewson and Hager, 1979). Horseradish roots and the sap of fig trees are the richest source of plant peroxidases. 

In addition to plant and animal sources, peroxidases are also found in mould, bacteria and microorganisms. A peroxidase from the mould Caldariomyces fumago, chloroperoxidase, has been isolated and characterised. Like the plant peroxidases it has ferriprotoporphyrin IX as the prosthetic group. In many of its chemical and physical properties chloroperoxidase is similar to horseradish peroxidase, but it has the unique ability amongst peroxidases to catalyse the oxidation of chloride ion (Hager et al., 1966 Morris and Hager, 1966). 

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