Monooxygenation reaction

Gibson DT, Resnick SM, Lee K, Brand JM, Torok DS, Wackett LP, Schocken MJ, Haigler BE (1995) Desaturation, dioxygenation, and monooxygenation reactions catalysed by naphthalene dioxygenase from Pseudomonas sp. strain 9S16-4. J Bacteriol 111 2615-2621. 

Fig. 1. The overall reaction catalyzed by NOS and a schematic representation of the three main NOS isoforms. L-Arg is first converted to JV-hydroxy-L-Arg in a P450-like monooxygenation reaction requiring two electrons and one O2 molecule. In the second step, Ai-hydroxy-L-Arg to NO and L-citrulline, only one electron and one O2 molecule are required. nNOS, neuronal NOS (neural system) iNOS, inducible NOS (immune system) eNOS, endothelial NOS (cardiovascular system).

The most numerous and most complex monooxygenation reactions are those employing a type of heme protein called cytochrome P-450. This cytochrome is usually present in the smooth ER rather than the mitochondria. Like mitochondrial cytochrome oxidase, cytochrome P-450 can react with 02 and bind carbon monoxide, but it can be differentiated from cytochrome oxidase because the carbon monoxide complex of its reduced form absorbs light strongly at 450 ran—thus the name P-450. 

Table 3 Examples of Monooxygenation Reactions Catalyzed by Flavoenzymes...

Though the investigation of photocatalytic oxygenations performed of the laboratory scale are often motivated by attempts to understand and mimic the catalytic cycle of cytochrome P450 (a natural catalyst of monooxygenation reactions), the results obtained [159, 253, 266] could be applied to industrial processes as well. 

Action mechanisms and kinetic features of catalases, peroxidases and monooxygenases. Catalytic system selection for conjugated dehydrogenation, epoxidation and monooxygenation reactions. 

Monooxygenation reactions involve the reduction of one atom of molecular oxygen to water and the incorporation of the other oxygen atom into the substrate [Eq. (9.1)]. The electrons involved in the reduction of CYP are transferred from NADPH by another enzyme called NADPH-cytochrome P450 oxidoreductase (CYPOR). 

Monooxygenations are those oxidations in which one atom of molecular oxygen is reduced to water while the other is incorporated into the substrate. Microsomal monooxygenation reactions are catalyzed by nonspecific enzymes such as the flavin-containing monooxygenases (FMOs) or the multienzyme system that has cytochrome P450s (CYPs) as the terminal oxidases. 

The majority of synthetic reactions in mammalian cells takes place in the cytosol. The intramitochondrial localization of transhydrogenase excludes a direct participation in these anabolic processes. Substrate shuttle mechanisms (176, 177) are required to allow for the interaction between intra- and extramitochondrial nicotinamide nucleotide-dependent reactions. In the first instance transhydrogenase can be regarded to be functionally related to intramitochondrial NADP-linked reactions. A number of studies on isolated mitochondria have elaborated these relationships in some detail, in particular with regard to mitochondrial monooxygenation reactions and to the metabolism of glutamate and isocitrate. 

Figure 8.2 Generalized scheme showing the catalytic cycle of cytochrome P450 enzymes in monooxygenation reactions. Fe = iron atom in P450 heme. RH = substrate. ROH = product. b5 = cytochrome bs. ox and red indicate the reduced and (1 electron) oxidized states of the reductase involved in the electron transfer. See text for details. (From Guengerich, F.P., Client. Res. Toxicol. 14, 611, 2001. With permission.)...

The biocatalysts capable of performing monooxygenation reactions are of special interest from a catalytic point of view, since in these reactions transfer of one of the oxygen atoms from molecular oxygen to the substrate occurs. The overcill reaction catalyzed by monooxygenases is... 

This C(4a)-hydroperoxyflavin intermediate is the active form of the cofactor in a monooxygenation reaction, leading to the hydroxylation of aromatic substrates. The reaction mechanism is schematically depicted in Fig. 4.81. Table 4.3... 

Cytochromes P450. Monooxygenation reactions are of major significance in drug metabolism and are mediated by various enzymes that differ markedly in their structure and... 

Some typical monooxygenation reactions catalyzed by P-450 are listed in Table I (75). Actually, the enzyme produces a strong oxidant in these reactions, but the precise reactive species in these oxygenations is still obscure. In the following sections, we will describe, step by step, what is known of the oxygen activation mechanism of P-450. 

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