Oxygenase, microsomal

P450 Mono-oxygenase System. Figure 1 (a) Components of the microsomal P450 mono-oxygenase system, (b) Components of the mitochondrial P450 mono-oxygenase system. 

Figure 32-12. Schematic representation of the microsomal heme oxygenase system. (Modified from Schmid R, McDonough AF in The Porphyrins. Dolphin D [editor]. Academic Press, 1978.)...

The major mono oxygenases in the endoplasmic reticulum are cytochrome P450s—so named because the enzyme was discovered when it was noted that preparations of microsomes that had been chemically reduced and then exposed to carbon monoxide exhibited a distinct peak at 450 nm. Among reasons that this enzyme is important is the fact that approximately 50% of the drugs humans ingest are metabolized by isoforms of cytochrome P450 these enzymes also act on various carcinogens and pollutants. 

Kirchin MA, A Wiseman, DR Livingstone (1992) Seasonal and sex variation in the mixed-function oxygenase system of digestive gland microsomes of the common mussel, My til us edulis L. Comp Biochem Physiol lOlC 81-91. 

Sunderman, F.W., Jr., M.C. Reid, L.M. Bibeau, and J.V. Linden. 1983. Nickel induction of microsomal heme oxygenase activity in rodents. Toxicol. Appl. Pharmacol. 68 87-95. 

Tynes, R. and Hodgson, E. (1984). The measurement of FAD-containing oxygenase activity in microsomes containing cytochrome P-450.Xenobiotica 14 515-520. 

Both mirex and chlordecone are microsomal enzyme inducers, and as such enhance the metabolism of compounds oxidized or reduced by the mixed function oxygenase system. For... 

Coon, M.J., Ballou, D.P., Haugen, D.A., Krezoski, S.O., Nordblom, G.D. and White, R.E. Purification of membrane-bound oxygenases isolation of two electrophoretically homogeneous forms of liver microsomal cytochrome P-1+50. 

Cytochrome P-450 has been characterized in four stable states [Fe, Fe " RH, Fe RH, (O2—Fe ) RH (metastable)] during its oxygenase reaction cycle. In the complete native system a flavoprotein and a redoxin (putidaredoxin) act as electron donors but also as effectors that complement the cytochrome. In the more complex microsomal system the sequence and intermediates are less well defined the electron-transfer chain contains two flavoproteins and one cytochrome, whose interactions with cytochrome P-450 are still the subject of great controversy. 

Cyclo-oxygenase inhibition. Ethanol (95%) extract of the dried fruit, administered to sheep, was active on microsomes, IC50 28.1... 

N-oxidation. The oxidation of nitrogen in tertiary amines, amides, imines, hydrazines, and heterocyclic rings may be catalyzed by microsomal enzymes or by other enzymes (see below). Thus the oxidation of trimethylamine to anN-oxide (Fig. 4.19) is catalyzed by the microsomal FAD-containing mono oxygenase. The N-oxide so formed may undergo enzyme-catalyzed decomposition to a secondary amine and aldehyde. This N to C transoxygenation is mediated by cytochromes P-450. The N-oxidation of 3-methylpyridine, however, is catalyzed by cytochromes P-450. This reaction may be involved in the toxicity of the analogue,... 

Bartsch, H., Malaveille, C., Barbin, A. Planche. G. (1979) Mutagenic and alkylating metabolites of halo-ethylenes, chlorobutadienes and dichlorobutenes produced by rodent or human liver tissues. Evidence for oxirane formation by P450-linked microsomal mono-oxygenases. Arch. Toxicol., 41, 249-277... 

Ferris, J. P., Fasco, M. J-, Stylianopoulou, F. L, Jerina, D. M., Daly, J. W. Jeffrey, A. M. (1973). Mono-oxygenase activity in Cunninghamella bainieri Evidence for a fungal system similar to liver microsomes. Archives of Biochemistry and Biophysics, 156, 97-103-... 

Related flavin hydroxylases act at nucleophilic positions on a variety of molecules393,402 including phenol,403 salicylate,404 anthranilate,405 p-c resol,406 4-hydroxyphenylacetate,407,408 and 4-aminobenzoate.409 Various microsomal flavin hydroxylases are also known 410 Flavin peroxide intermediates are also able to hydroxy late some electrophiles.411 For example, the bacterial cyclohexanone oxygenase catalyzes... 

It has to be pointed out that imines do not only serve as substrates for the N-oxygenase(s) when added exogenously to assay mixtures, but are also acted upon by these enzymes when metabolically formed from primary amines. Thus, it is interesting to note that benzylmethyl ketimine has been proposed as an intermediate in microsomal... 

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