Enzymatic dismutation

As can be produced by equations (9) and (10) and by the spontaneous or enzymatic dismutation of O J (Scheme 3), its reaction with deoxyhemoglobin and with methemoglobin must also be considered ... 

We will limit our discussion to catalase and peroxidase as the enzymes—hydrogen peroxide killers. In its turn, hydrogen peroxide is formed in vivo in two-electron 02 reduction and enzymatic dismutation of 02 radicals in accordance with the mechanism, which includes alternating reduction and Cu2+ reoxidation in the active site of the enzyme during consecutive acts of interaction with 02 [79, 80] ... 

The overall advantage of enzymatic dismutation of superoxide is illustrated in Fig. 2, where the rate constants for dismutation for three of the enzyme classes are plotted as a function of pH on a graph that also has the self-dismutation rate constants for superoxide/perhy-droxyl radical plotted as a function of pH. It should be noted, though, that the enzymatic rate constants are catalytic and therefore only depend upon the enzyme concentiation whereas the self-dismu-tation is bimolecular in superoxide. This leads to very important ramifications with regards to the enzyme-substrate concentrations. Figure 3 illustrates three different scenarios and shows the relative rate constants at different extremes of [S0D] [02 ]. The in vivo implications of this are profound. 

Reduction Kinetics of the Type 3 Copper. Quantitative assessment of the complex kinetic behavior at 330 nm is diflScult. This diflSculty probably is partially caused by the small and varied contribution from the production and decay of the substrate radical species (63), a feature that is revealed when runs at at various wavelengths are compared. The decay rate of the radical, presumably decay by non-enzymatic dismutation, has a magnitude similar to the reduction rate of the type 3 copper. In the experiments with ascorbate as substrate. 

SODs are differentiated mainly by the redox-active metal in the active site copper, manganese, or iron. The iron and manganese SODs are structurally similar (5-11) and are structurally distinct from the Cu,Zn SOD (12). The dramatic features of these enzymes are that they catalytically dismutate superoxide at rates that are not only diffusion controlled but have been shown to be electrostatically facilitated (13). In these systems, modifications of amino acid residues near the active site have been shown to alter the enzymatic activity, indicating that superoxide is electrostatically drawn into the active site channel (14). In addition, in contrast to the spontaneous dismutation rate of 02 and the dismutation rates of 02 by many metal complexes, all of which are pH dependent, the enzymatic dismutation rate is largely pH independent over the pH range (5-10). 

Due to the rapidity of the spontaneous dismutation reactions, the steady-state concentrations of 02 achieved by chemical or by enzymatic reactions are usually quite low. The physical methods for detecting 02, although direct and unequivocal, are restricted to measurements of steady-state concentrations and are thus often found to lack of sensitivity. For distince, due to the reason mentioned above, when the EPR method was employed for studying the 02 production by xanthine oxidase, it was necessary to use a high concentration of the reactants and to work at elevated pH so... 

The principle of antioxidant detection is shown in Fig. 17.3. Superoxide was enzymatically produced and dismutated spontaneously to oxygen and H202. Under controlled conditions of superoxide generation such as air saturation of the buffer, optimal hypoxanthine concentration (100 pM) and XOD activity (50mU ml-1) a steady-state superoxide level could be obtained for several min (580-680 s). Since these steady-state superoxide concentrations can be detected by the cyt c-modified gold electrode, the antioxidate activity can be quantified from the response of the sensor electrode by the percentage of the current decrease. 

Protons are in general indispensable for the dismutation of superoxide (Eq. (4)). Also in the case of its dismutation catalyzed by a metal center, two protons are needed for the dissociation of the product (H2O2) from the metal center (Scheme 9). Therefore, a complex which can accept two protons upon reduction and release them upon oxidation is an excellent candidate for SOD activity. The studies on proton-coupled electron transfer in Fe- and Mn-SODs 48), demonstrated that the active site of MnSOD consists of more than one proton acceptor (Scheme 10). Since the assignment of species involved in proton transfer is extremely difficult in the case of enzymatic systems, relevant investigations on adequate model complexes could be of vast importance. H2dapsox coordinates to Fe(II) in its neutral form, whereas in the case of Fe(III) it coordinates in the dapsox form. Thus, oxidation and reduction of its iron complex is a proton-coupled electron transfer process 46), which as an energetically favorable... 

Phytochemical reduction must be regarded as a special case of oxidation-reduction. Since it is enzymatically conducted it should be distinguished from the analogously formulated Cannizzaro reaction. For this reason Neuberg, Hirsch and Reinfurth suggested the name dismutation for the physiological process, and in the last 25 years... 

Diphosphothymidine, I, 242 Diplococcua pneumoniae, polysaccharides formed by, II, 221 Disaocharides, III, 130 enzymatic syntheses of, V, 29-48 oxidation of, III, 132, 145 Dismutation, the term, IV, 101 Disproportionation, IV, 102 Dissociation constants, of hypobromous, hypochlorous and hypoiodous acids,... 

The biosynthetic pathway of riboflavin in B. subtilis is outlined in Fig. 8.28. The starting compound GTP is, as well as the other purines, tightly regulated as these normally are not present in the cell in appreciable amounts [140]. The final step is a dismutation of DRL into riboflavin and ArP. The six enzymatic activities involved (not counting the phosphatase) are encoded by four genes, which are closely grouped on the rib operon [139]. 

Enzymatic oxidation of chlorpromazine by peroxidase-H202 and catalase-H202 systems has been reported. The red color which forms intermediately is due to the free radical the great stability of the latter causes further enzymatic oxidation to the phenazathio-nium cation to play an important part in the decay of the radical, along with dismutation. ... 

It was not until thirty years after the copper-containing protein erythrocuprein was discovered (T. Mann, D. Kei-LiNG, 1939) that its enzymatic nature was proved. At that time, this protein was shown to convert superoxide radicals into molecular oxygen and H2O2 (J.M. McCord, 1969 I. Fridovich, 1969) it was Eridovich who coined the term superoxide dismutase (SOD). This presumably most important of antioxidants accelerates the conversion of superoxide radicals 10,000 times more effectively than spontaneous dismutation. 

Nitric oxide is not in itself very reactive or particularly toxic. However, its interaction with other oxidants may yield products whose toxicity may result of significance. Such is the case of peroxynitrite (ONOO ) which is formed in a non-enzymatic reaction between NO and O2-. This reaction follows a 1 1 stoichiometry and it has a very fast reaction speed (6.7 X 10 mol/L s [40] which is 3 times higher than the capacity of O2 dismutation by SOD and around 1000 times greater than the reaction of NO with iron-sulfiir clusters [41 ]. 

The four important enzymatic components of the cellular antioxidant defense system. Superoxide dismutase (SOD) catalyzes the dismutation of superoxide (02-) to peroxide. Catalase reduces peroxide to H20. GSH peroxidase also detoxifies peroxide by reducing it to H20. GSH reductase re-reduces the oxidized glutathione (GSSG) to GSH. The NADPH required for the reduction of GSSG to GSH is primarily supplied by the oxidation of glucose via the pentose phosphate pathway. (Based on Mottet, N.K., Ed. Environmental Pathology. Oxford University Press, New York, 1985.)... 

It has recently been shown that organic Cu-complexes increase the decay rate of 02 in natural waters. Voelker et al. [30] found that organically complexed copper significantly lowered steady state 02 concentrations in marine waters. Goldstone and Voelker [78] also demonstrated that DOM contains a non-metallic, non-enzymatic fraction that can catalyze superoxide dismutation. When copper-DOM reactions are considered, estimated steady state concentrations of 02 in coastal waters are 100- to 1000-fold lower than predicted concentrations, which only consider its decay through bimolecular dismutation [78]. Thus, the photochemical redox cycling of DOM via 02 reactions may... 

The catalyzed disproportionation (dismutation) of superoxide has been studied extensively, particularly in regard to its enzymatic catalysis by the superoxide dismutases (SODs). The superoxide dismutases are metalloenzymes and can have Cu-Zn, Fe, Mn, or Ni active sites. Simple inorganic species can also catalyze the reaction.28 For example, catalysis by Fe2+/Fe(III) at pH 7.2 has the rate law... 

Hydrogen peroxide is not merely dismutated by catalase, but used as substrate in a second enzyme cascade reaction producing propylene oxide [123 1251. In an alternative process 1261 the reduction step was performed enzymatically using aldose reductase and formate dehydrogenase for NADH regeneration. Thus, essentially glucose free D-fructose was obtained. 

In mammalian systems, nitroaromatic compounds are further reduced to amines and/or hydroxylamines, which may subsequently form DNA and protein adducts. These stable metabolites may be formed by the reduced oxygen tension and high local single-electron transferring enzyme concentration, for example, P-450R in microsomes may favor the free radical dismutation over their reoxidation by oxygen (Equation 9.8). Subsequently, the nitroso compounds formed (Equations 9.7 and 9.8) will be reduced to hydroxylamines (ArNHOH) and/or amines (ArNHj). The stable metabolites may also be formed by the two-electron reduction of nitroaromatics by certain flavoenzymes. In fact, the enzymatic two-electron reduction may be considered as the four-electron reduction, since after the first two-electron (hydride) transfer, the reduction of an intermediate nitroso compound to hydroxylamine (ArNHOH) proceeds faster [55] ... 

In particular, LADHs catalyze the reversible dehydrogenation of primary and secondary alcohols to aldehydes and ketones, respectively. Other enzymatic activities of LADHs are aldehyde dismutation and aldehyde oxidation. The physiological role, although surely related to the metabolism of the above species, is not definitely settled. Much effort is being devoted to understanding the mechanism of action of this class of enzymes, which have obvious implications for the social problem of alcoholism. 

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