Monooxygenase mechanism

Analogous side-chain oxidations occur in various biosynthetic pathways. The neurotransmitter norepinephrine, for instance, is biosynthesized from dopamine by a benzylic hydroxylation reaction. The process is catalyzed by the copper-containing enzyme dopamine /3-monooxygenase and occurs by a radical mechanism. A copper-oxygen species in the enzyme first abstracts the pro-R benzylic hydrogen to give a radical, and a hydroxyl is then transferred from copper to carbon. 

Monooxygenase Protein System Structure, Component Interactions, and Hydroxylation Mechanism Katherine E. Liu and Stephen J. Lippard... 

Resistance mechanisms associated with changes in toxicokinetics are predominately cases of enhanced metabolic detoxication. With readily biodegradable insecticides such as pyrethroids and carbamates, enhanced detoxication by P450-based monooxygenase is a common resistance mechanism (see Table 4.3). 

PAHs can be bioconcentrated or bioaccumulated by certain aquatic invertebrates low in the food chain that lack the capacity for effective biotransformation (Walker and Livingstone 1992). Mollusks and Daphnia spp. are examples of organisms that readily bioconcentrate PAH. On the other hand, fish and other aquatic vertebrates readily biotransform PAH so, biomagnification does not extend up the food chain as it does in the case of persistent polychlorinated compounds. As noted earlier, P450-based monooxygenases are not well represented in mollusks and many other aquatic invertebrates (see Chapter 4, Section 4.2) so, this observation is not surprising. Oxidation catalyzed by P450 is the principal (perhaps the only) effective mechanism of primary metabolism of PAH. 

Cytochrome P450 is considered the most versatile biocatalyst known. The actual reaction mechanism is complex and has been briefly described previously (Figure 11-6). It has been shown by the use of that one atom of oxygen enters R—OH and one atom enters water. This dual fate of the oxygen accounts for the former naming of monooxygenases as mixed-function oxidases. The reaction catalyzed by cytochrome P450 can also be represented as follows ... 

DMN oxidative demethylation has been shown to be a liver mi-crosome cytochrome P-450 monooxygenase (10) Lotlikar et al. (11) found that a reconstituted enzyme system, consisting of cytochrome P-450, NADPH-cytochrome P-450 reductase and phosphatidyl choline was effective in catalyzing the demethylation of DMN. The most commonly accepted mechanism for the oxidative demethylation of DMN and, by extension, of other dialkyInltrosamlnes is shown in Scheme 1. 

Carotene cleavage enzymes — Two pathways have been described for P-carotene conversion to vitamin A (central and eccentric cleavage pathways) and reviewed recently. The major pathway is the central cleavage catalyzed by a cytosolic enzyme, p-carotene 15,15-oxygenase (BCO EC 1.13.1.21 or EC 1.14.99.36), which cleaves p-carotene at its central double bond (15,15 ) to form retinal. Two enzymatic mechanisms have been proposed (1) a dioxygenase reaction (EC 1.13.11.21) that requires O2 and yields a dioxetane as an intermediate and (2) a monooxygenase reaction (EC 1.14.99.36) that requires two oxygen atoms from two different sources (O2 and H2O) and yields an epoxide as an intermediate. ... 

STUDIES OF THE SOLUBLE METHANE MONOOXYGENASE PROTEIN SYSTEM STRUCTURE, COMPONENT INTERACTIONS, AND HYDROXYLATION MECHANISM... 

Basch, H., Mogi, K., Musaev, D. G., Morokuma, K., 1999, Mechanism of the Methane —> Methanol Conversion Reaction Catalyzed by Methane Monooxygenase A Density Functional Study , J. Am. Chem. Soc., 121, 7249. 

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