Catalase mechanism

A proposed catalase mechanism, formulated before the x-ray structure of the reduced enzyme (Figure 10) had been elucidated, is shown in Scheme 1 [96]. 

Scheme 1 Catalase mechanism showing schematically the bis(carboxylato) bridged dinuclear metal centers. DH/Dy hydron donor/acceptor species. (After Refs. 7, 96.)...

Shimizu N, Kobayashi K, Hayashi K (1984) The reaction of superoxide radical with catalase. Mechanism of the inhibition of catalase by superoxide radical. J Biol Chem 259 4414-4418... 

The chemistry of the colorful, perplexing, and challenging problem of catalase mechanism has been set forth in numerous reviews. Those by Brill 16), Nicholls and Schonbaum (f ), and most recently, Deisseroth and Bounce (15) summarize the fundamental properties of catalase and its reactions, and their physiological implications. Further, Feinstein 19) and Aebi 20-22) have presented detailed evaluations of acatalasemia, and de Duve 23) and others have discussed catalase biosynthesis 23-26), its intracellular location 23-25) and its turnover 24, 26-28). These facets of the catalase problem will not be reiterated. Instead, a brief synopsis of the enzyme characteristics will be followed by a discussion on the nature of the active site and the chemistry of the catalase reaction mechanism. 

At least two quasistable reaction intermediates, which differ in the nature of the Fe-bound ligands and the formal Fe oxidation state, referred to as compounds I and II, have been identified and characterized by a number of biophysical techniques (Walsh, 1979). Both of these species are spectrally distinct from the resting state of the native enzyme. In favorable cases, suitable reaction conditions or substrates may be chosen to conduct rapid kinetic investigations of the individual catalytic steps in the peroxidases or catalase mechanisms. 

The proposed catalase mechanism is depicted in Scheme 11.1. Hydrogen peroxide decomposition is initiated by (a) the binding of H2O2 to the Mn "-Mn " dinuclear center, and this is followed by (b) reduction to the Mn"-Mn" intermediate and concomitant oxidation of the peroxide to O2 [33, 34]. Subsequent binding of a second molecule of H2O2 to the Mn -Mn" species (c) is followed by the reduction of H2O2 to H2O and the oxidation of the Mn"-Mn" species (d), which closes the catalytic cycle [17]. 

The free-radical defence mechanisms utilized by the brain are similar to those found in other tissues. The enzymes SOD, catalase, glutathione peroxidase, and the typical radical scavengers, ascorbate, vitamin E and vitamin A are present in the brain, as they are in peripheral tissues. However, the brain may actually be slightly deficient in some of these defence mechanisms when compared to the amounts present in other tissues. 

Future research should also focus its attention on the factors/mechanisms that regulate free-radical activity in vivo. The complex interrelationship between cellular and extracellular levels of antioxidants needs to be clarified, and factors that govern the synthetic rate of the scavenging enzymes, for example, SOD or catalase will provide further insight into cellular redox control. 

Catalase is one of the oldest known enzymes and was developed when life became aerobic, i.e. when organisms started to use oxygen. When a cell uses oxygen in its metabolism HP is very often produced as a by-product. However HP is toxic to the cells, so they need some defence mechanism. Catalase was invented by the evolution to protect living cells from HP. 

Garlic s proven mechanisms of action include (a) inhibition of platelet function, (b) increased levels of two antioxidant enzymes, catalase and glutathione peroxidase, and (c) inhibition of thiol enzymes such as coenzyme A and HMG coenzyme A reductase. Garlic s anti-hyperlipidemic effects are believed to be in part due to the HMG coenzyme A reductase inhibition since prescription medications for hyperlipidemia have that mechanism of action (statins). It is unknown whether garlic would have the same drug interactions, side effects, and need for precautions as the statins. 

Catalases and peroxidases both promote H2O2 reduction by mechanisms that involve ferryl intermediates. Catalases differ from peroxidases by their ability to use H2O2 both as an electron acceptor and as donor, thus catalysing the disproportionation reaction (catalatic activity) (equation 1) ... 

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