Halide Activation by Heme Peroxidases: Theoretical Predictions on Putative Adducts of Halides with Compound I

Silaghi-Dumitrescu, Radu

doi:10.1002/ejic.200800732

Cited by 17 publications

(10 citation statements)

References 24 publications

(29 reference statements)

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“…[9a] Further studies on haloperoxidases also investigated the reactivity of Cpd I models with halides to form hypohalide products. [15] However, the direct reaction of Cpd I with halogenated compounds has never been investigated in detail.…”

Section: Introductionmentioning

confidence: 99%

Metabolism of Halogenated Alkanes by Cytochrome P450 enzymes. Aerobic Oxidation versus Anaerobic Reduction

Ji¹,

Zhang²,

Liu³

et al. 2014

Chemistry An Asian Journal

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The cytochromes P450 are a large class of heme-containing enzymes that catalyze a broad range of chemical reactions in biosystems, mainly through oxygen-atom transfer to substrates. A relatively unknown reaction catalyzed by the P450s, but very important for human health, is the activation of halogenated substrates, which may lead to toxicity problems. However, its catalytic mechanism is currently unknown and, therefore, we performed a detailed computational study. To gain insight into the metabolism of halogenated compounds by P450 enzymes, we have investigated the oxidative and reductive P450-mediated activation of tetra- and trichloromethane as halogenated models with density functional theory (DFT) methods. We propose an oxidative halosylation mechanism for CCl4 under aerobic conditions by Compound I of P450, which follows the typical Groves-type rebound mechanism. By contrast, the metabolism of CHCl3 occurs preferentially via an initial hydrogen-atom abstraction rather than halosylation. Kinetic isotope effect studies should, therefore, be able to distinguish the mechanistic pathways of CCl4 versus CHCl3 . We find a novel mechanism that is different from the well accepted P450 substrate activation mechanisms reported previously. Moreover, the studies highlight the substrate specific activation pathways by P450 enzymes leading to different products. These reactivity differences are rationalized using Marcus theory equations, which reproduce experimental product distributions.

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Section: Introductionmentioning

confidence: 99%

Metabolism of Halogenated Alkanes by Cytochrome P450 enzymes. Aerobic Oxidation versus Anaerobic Reduction

Ji¹,

Zhang²,

Liu³

et al. 2014

Chemistry An Asian Journal

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“…Typical affinities of heme enzymes for peroxide are closer to the range of 1 mM. From this point of view, the PX purified here constitutes a particular exception, rivalling the non-heme peroxidases in this respect [16]. Figure 9 shows the pH dependence of the activity, for the two enzymes purified -AO and PX.…”

Section: Michaelis-menten Analysismentioning

confidence: 77%

“…By far the most common peroxidases are the ones featuring a heme at the active site (as seen, e.g., in horseradich peroxidase HRP or in chloroperoxidase CPO) -to the extent that the term "peroxidase" is generally assumed to refer to heme-containg peroxidases; other types of peroxidases feature active sites based on cysteine, or selenocysteine, or vanadium, or a binuclear di-iron center. The practical applications of peroxidases are vast and have been described elsewhere [16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Isolation, purification and characterization of ascorbate oxidase and peroxidase from Cucurbita pepo medullosa

Crainic¹,

Moţ²,

Silaghi‐Dumitrescu³

2019

Studia UBB Chemia

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Ascorbate oxidase is a well-known copper-containing enzyme however, its biological role and mechanism are still unclear. Reported here is a new protocol for purification of ascorbate oxidase from Cucurbita pepo medullosa (field pumpkin), with improved yields. The enzyme is biochemically characterized, including Michaelis-Menten parameters. Also, purification and characterization of the peroxidase from the same source is described, featuring an unusually high affinity for hydrogen peroxide(low-micromolar).

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“…This approach has previously yielded satisfactory results on similar complexes. [14,23,[27][28][29][30] Charges and spin densities were derived from NBO population analyses after DFT geometry optimization.…”

Section: Discussionmentioning

confidence: 99%

Hydrocarbon Oxygenation by Metal Nitrite Adducts: Theoretical Comparison with Ferryl‐Based Oxygenation Agents

Silaghi-Dumitrescu

Макаров

2010

Eur J Inorg Chem

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Metal nitrite adducts can, under certain conditions, insert one of their oxygen atoms into hydrocarbons. This reaction is to some extent reminiscent of the process whereby high‐valent ferryl (formally FeIV=O) species such as compound I in hemoproteins also insert an oxygen atom into hydrocarbons. Density functional theory (DFT) data are shown here, examining the oxygenation ability of ferrous and ferric nitrite adducts in octahedral coordination environments modeling those seen in hemoproteins where such adducts are well characterized. A comparison of these results with those obtained with similar methods on formal FeV–oxido models of hemoprotein compound I models relevant for such enzymes as cytochrome P450 and chloroperoxidase reveals a key role of the redox potential in dictating oxygenation ability, in good agreement with interpretations previously given by Green and co‐workers.

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Halide Activation by Heme Peroxidases: Theoretical Predictions on Putative Adducts of Halides with Compound I

Cited by 17 publications

References 24 publications

Metabolism of Halogenated Alkanes by Cytochrome P450 enzymes. Aerobic Oxidation versus Anaerobic Reduction

Metabolism of Halogenated Alkanes by Cytochrome P450 enzymes. Aerobic Oxidation versus Anaerobic Reduction

Isolation, purification and characterization of ascorbate oxidase and peroxidase from Cucurbita pepo medullosa

Hydrocarbon Oxygenation by Metal Nitrite Adducts: Theoretical Comparison with Ferryl‐Based Oxygenation Agents

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