Cytochrome containing monooxygenase system

Shimada, T. and Y. Sawabe. 1983. Activation of 3,4,3, 4 -tetrachlorobiphenyl to protein-based metabolites by rat liver microsomal cytochrome P-448 containing monooxygenase system. Toxicol. Appl. Pharmacol. 70 486-493. 

Figure 2. Chemical mechanism for the metabolism of parathion to paraoxon by the Cytochrome P-450-containing monooxygenase system (6)...

Fourth, certain segments of the nephron have a capacity for metabolic bioactivation. For example, the proximal and distal tubules contain isozymes of the cytochrome P450 monooxygenase system that may mediate intrarenal bioactivation of several protoxicants. Additionally, prostaglandin synthetase activity in medullary and papillary interstitial cells may be involved in cooxidation of protoxicants, resulting in selective papillary injury. 

Cytochrome P450 monooxygenase Flavin-containing monooxygenase system Alcohol dehydrogenase and aldehyde dehydrogenase Monoamine oxidase Co-oxidation peroxides... 

Several studies have shown that the reactive binding species generated by 1,1-dimethylhydrazine metabolism may be free radical intermediates. Rat liver microsomes and rat hepatocytes are capable of metabolizing 1,1-dimethylhydrazine to form methyl radical intermediates (Albano et al. 1989 Tomasi et al. 1987). The formation of tliese radicals was inhibited by the addition of inhibitors of cytochrome P-450 (SKF 525A, metyrapone, and carbon monoxide) and inhibitors of the flavin-containing monooxygenase system (methimazole). The formation of free radicals could also be supported nonenzymatically by the presence of copper ion (Tomasi et al. 1987). These data indicate that at least two independent enzyme systems and one nonenzymatic pathway may be involved in the metabolism of... 

Since reactive intermediates are produced as a result of the metabolism of hydrazines, the administration of inhibitors of the cytochrome P-450 or the flavin-containing monooxygenase system may offer some protective effect. For example, disulfiram, an inhibitor of cytochrome P4501 lEl (Guengerich et al. 1991), decreased the oxidation of azomethane (a metabolite of 1,2-dimethylhydrazine) to azoxymethane, and the further oxidation of azoxymethane to methylazoxymethanol (Fiala et al. 1977). The inhibition of... 

The microsomal fraction consists mainly of vesicles (microsomes) derived from the endoplasmic reticulum (smooth and rough). It contains cytochrome P450 and NADPH/cytochrome P450 reductase (collectively the microsomal monooxygenase system), carboxylesterases, A-esterases, epoxide hydrolases, glucuronyl transferases, and other enzymes that metabolize xenobiotics. The 105,000 g supernatant contains soluble enzymes such as glutathione-5-trans-ferases, sulfotransferases, and certain esterases. The 11,000 g supernatant contains all of the types of enzyme listed earlier. 

Adults injected ip for 3 days at 80 mg/kg BW daily then killed 24 h after last injection Heme destruction in the P-448-containing reconstituted monooxygenase system reactive epoxide, or possibly nonepoxide, intermediate metabolites may participate in cytochrome P-448 destruction 24... 

Parathion is one of a class of phosphorothionate triesters widely used as insecticides. These compounds exert their toxic effects in insects and mammals by inhibiting the enzyme acetylcholinesterase. The phosphorothionates, in general, are relatively poor inhibitors of acetylcholinesterase but are converted by the cytochrome P-450-containing monooxygenase enzyme systems in insects and mammals to the corresponding phosphate triesters that are potent inhibitors of this enzyme. 

Parathion is also metabolized to diethyl phosphorothioic acid and -nitrophenol in a reaction requiring a cytochrome P-4Jg-containing monooxygenase enzyme system (, 4). Studies with H. 0 have indicated that water in addition to molecular oxygen and NADPH is required in this reaction ( ). Diethyl phosphate and -nitro-phenol can also be formed from parathion in a monooxygenase-catalyzed reaction (6). 

Figure 6. Elution profile of protein, radioactivity, and thiocyanate from a Sepha-dex G-25 column of reconstituted monooxygenase system from rat liver that had been incubated with [ 5] parathion. The 5-mL incubation mixture contained 20 nmol Cytochrome P-450 (specific activity 16.4 nmol/mg protein), 5 units NADPH-Cytochrome c reductase, 600 fig dilauroyl L-3-phosphatidylchoUne, 600 fig sodium deoxycholate, and 1 X IO M p 5] parathion. The remainder of the incubation mixture is described in Figure 4. The incubation time was 5 min. One-milliliter fractions were collected. The radioactivity (x) represents cpm/0.1 mL. The OOggo (o) was measured on each 1-mL fraction (20).

Microsomal flavin-containing monooxygenases. As well as the cytochromes P-450 MFO system, there is also a system, which uses FAD. This flavin-containing monooxygenase or FMO enzyme system is found particularly in the microsomal fraction of the liver, and the monomer has a molecular weight of around 65,000. Each monomer has one molecule of FAD associated with it. The enzyme may accept electrons from either NADPH or NADH although the former is the preferred cofactor. It also requires molecular oxygen, and the overall reaction is as written for cytochromes P-450 ... 

Monooxygenation of xenobiotics are catalyzed either by the cytochrome P450 (CYP)-dependent monooxygenase system or by flavin-containing monooxygenases (FMO). 

Virgin mammary glands from female Sprague-Dawley rats have been shown to contain an inducible cytochrome P-450 in the microsomal monooxygenase system (29). It is reasonable to assume that dietary... 

Fumes B, Schlenk D. Extrahepatic metabolism of carbamate and organophosphate thioether compounds by the flavin-containing monooxygenase and cytochrome P450 systems. Drug Metab Dispos 2005 33 214—218. 

Monooxygenase systems consist of several components, the most prominent of which is cytochrome P450. Cytochromes are a group of proteins containing a b-... 

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. 

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