Catalytic cycle 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... 

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.

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

III). As a byproduct of these two le equivalent oxidation steps, electron donors (designated as AH) are converted to free radicals (A ). The peroxidative cycle of catalase is about 1000-times slower than the catalytic cycle [120]. Since SA can act as a substrate for both of the steps constituting the peroxidative cycle (steps 3 and 4), it shunts the enzyme into this slower peroxidative cycle and thereby causes an inhibition of catalase activity. 

Although the exact sequence of intermediates seen in the P-450 reaction cycle is not observed with chloroperoxidase, one feature of the chloroperoxidase reaction cycle (Fig. 4) does occur for the P-450 system (Fig. 3). Addition of oxygen atom donors such as peroxides or iodosobenzene to P-450 state 2 (the enzyme-substrate complex) results in the formation of product, in a reaction that probably has state 7 as an intermediate. The first step of this alternative, short-circuit cycle, also called the peroxide shunt, is essentially identical to the first step of the chloroperoxidase catalytic pathway. 

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