Peroxide shunt

Fig. 5. Catalytic cycle of cytochrome P450. The substrate HR binds to the resting enzyme A to form intermediate B, which is reduced by one electron to form C and then reacts with dioxygen. The resulting ferric-peroxo intermediate D is reduced by one equivalent to form the transient oxyferrous intermediate E, which proceeds quickly to intermediate F with release of a molecule of water. F is designated Fe(V)=0 to indicate that it is oxidized by two equivalents greater than A and not to imply anything about the true oxidation state of the iron. Intermediate F then transfers an oxygen atom to the substrate to regenerate the resting enzyme. The peroxide shunt refers to the reaction of B with hydrogen peroxide to produce the intermediate F, which can then proceed to product formation.

Most characteristic for the catalytic cycle of heme monooxygenases is the activation of molecular dioxygen to an active FeO moiety and water. Only two out of four oxidation equivalents are thus used for the synthesis of oxygenated products. This fact is often used as a mechanistic possibility of a short-cut, the so-called peroxide shunt, where a... 

Although the peroxide shunt path to a ferryl intermediate is an attractive hypothesis, there is very little data to support the idea that the species obtained by this path are the same as, or similar to, that... 

Fig. 10.2. Catalytic cycle of P450 including the peroxide shunt pathway. RH is substrate, and ROH is product. The porphyrin molecule is represented as a parallelogram. The overall charge on the structures is shown to the left of each bracket. Intermediates 1, 2, 7, and 8 are neutral. Refer to text for a full description.

P450s are capable of utilizing an oxygen atom from peroxide to catalyze oxygen insertion without electron transport proteins or the NAD(P)H cofactor, through the peroxide shunt pathway ... 

Figure 15 The P450 catalytic cycle including uncoupling side reactions (Steps 10,11 and 12) and the peroxide shunt (Step 13)...

Cyt P450 ,ani Increased activity in peroxide shunt pathway, towards napthalene 5-20-fold 1-2 [512]... 

A critical issue in the use of P-450s as biocatalysts is the cost of the cofactors NADPH and NADH (to a lesser extent) required to support P-450-mediated activity. The first approach used to address this issue has been to exploit the peroxide shunt, that is, the ability of P-450s to use peroxides as surrogate oxygen donors, thereby bypassing the need for supplying electrons from a pyridine cofactor, by evolution of the P-450 to function more... 

An alternative reaction pathway, called the peroxide shunt, is obtained by the association of various oxygen atom donors (PhlO, C1O , ROOH, H2O2, KHSO5 and so on) with the high-spin iron(III) substrate-bound enzyme. Such additions lead directly the 0x0 species. 

The MMOR transfers electrons from NADH to the oxygen activation site on the iron-oxygen clusters on MMOH. The role of the MMOB is very complex and not yet clarified (31). The electrons from NADH can be replaced by chemical reduction of the two iron-oxygen clusters of MMOH (by, e.g., dithionite) in so-called single-turnover reactions by the MMOH alone (128). MMOH alone can also use the H2O2 reaction (2b) as a replacement for both electrons and oxygen (132) in a so-called peroxide shunt reaction. Both these results clearly demonstrate that the active site is on the MMOH, and that methanol formation does not involve the other two components. 

P. A compound K is probably formed (but it has not yet been observed) when the diferric enzyme is reacted with hydrogen peroxide to form compound Q. The peroxide shunt is the alternative pathway for turnover (133). It is analogous to such a shunt in cyt P450, and it was one strong indication of a similar reaction mechanism and similar hydroxylating species for the two enzymes (129, 133). 

The oxygen-binding step to the metal can occur after one electron reduction (cytochrome P450) M , or after two electron reduction (MMO) M" or while the peroxide shunt does not pass... 

Peroxo-diiron(III) complexes can undergo not only redox but also ligand substitution reactions. Liberation of H202 was observed in the reactions with phenols and carboxylic acids leading also to the respective phenolate or carboxylate iron(III) complexes.86 Hydrolysis of a peroxo-diiron(III) complex results in an oxo-diiron(III) species and hydrogen peroxide. Such reaction is responsible for the autoxidation of hemerythrin, but is very slow for the native protein due to hydrophobic shielding of the active site (Section 4.2.3).20 The hydrolysis of iron(III) peroxides is reversible, and the reverse reaction, the formation of peroxo intermediates from H202 and the (di)iron(III), is often referred to as peroxide shunt and is much better studied for model complexes. 

The electrophilic 0x0 of the Hangman platform is also susceptible to nucleophilic attack by the two-electron bond of olefins. The reaction parallels the peroxide shunt cycle (198-200) of cytochrome P450 and peroxidase enzymes while building on the results of the observed biomimetic catalase activity. The common olefins styrene and c/i-cyclooctene were chosen as substrates for epoxidation by the manganese HPX and HPD derivatives MnCKHPX-COaH) (33), The MnCl(HPX-C02Me) complex (34) and MnCl(HPD—CO2H) (35) with MnCl(TMP) as the standard baseline compound. 

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