Dependent Monooxygenase System

Monooxygenations, previously known as mixed-function oxidations, are those oxidations in which one atom of a molecule of oxygen is incorporated into the substrate while the other is reduced to water. Because the electrons involved in the reduction of CYPs or FMOs are derived from NADPH, the overall reaction can be written as follows (where RH is the substrate)  

The CYPs, the carbon monoxide-binding pigments of microsomes, are heme proteins of the b cytochrome type. Originally described as a single protein, there are now known to be more than 2000 CYPs widely distributed throughout animals, plants, and microorganisms. A system of nomenclature utilizing the prefix CYP has been devised 

The two most important difference spectra of reduced CYP are the well-known CO spectrum, with its maximum at or about 450 nm, and the type III spectrum, with two pH-dependent peaks at approximately 430 and 455 nm. The CO spectrum forms the basis for the quantitative estimation of CYP. The best-known type III ligands for CYP are ethyl isocyanide and compounds such as the methylenedioxyphenyl synergists and SKF 525A, the last two forming stable type III complexes that appear to be related to the mechanism by which they inhibit monooxygenations. 

In the catalytic cycle of CYP, reducing equivalents are transferred from NADPH to CYP by a flavoprotein enzyme known as NADPH-cytochrome P450 reductase. The evidence that this enzyme is involved in CYP monooxygenations was originally derived from the observation that cytochrome c, which can function as an artificial electron acceptor for the enzyme, is an inhibitor of such oxidations. This reductase is an essential component in CYP-catalyzed enzyme systems reconstituted from purified components. Moreover antibodies prepared from purified reductase are inhibitors of microsomal 

The possibility that the second electron is derived from NADH through cytochrome bs has been the subject of argument for some time and has yet to be completely resolved. Cytochrome bs is a widely distributed microsomal heme protein that is involved in metabolic reactions such as fatty acid desaturation that involve endogenous substrates. It is clear, however, that cytochrome bs is not essential for all 

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Boon, J.P., Van Arnhem, E., and Jansen, S. et al. (1992). The toxicokinetics of PCBs in marine mammals with special reference to possible interactions of individual congeners with cytochrome P450 dependent monooxygenase systems an overview. In C.H Walker and D. Livingstone (1992). Persistent Pollutants in Marine Ecosystems 119-160. 

Schwen, R.J. and G.J. Mannering. 1982a. Hepatic cytochrome P-450-dependent monooxygenase systems of the trout, frog and snake. II. Monooxygenase activities. Comp. Biochem. Physiol. 71B 437-443. 

Robacker KM, Kulkarni AP, Hodgson E. 1981. Pesticide induced changes in the mouse hepatic microsomal cytochrome P-450-dependant monooxygenase system and other enzymes. J Environ Sci Health (Part B Pestic Food Contam Agric Wastes) 16(5) 529-546. 

Yarbrough JD, Grimley JM, Alley EG. 1986a. Induction of the hepatic cytochrome P-450 dependent monooxygenase system by cis- and trans-5,10-dihydrogen mirex. Toxicol Lett 32 65-71. 

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

The biochemical mechanism of carbon tetrachloride toxicity has been investigated in detail. The cytochrome P-450-dependent monooxygenase system acts on CC14 in the liver to produce the C13C free radical ... 

The cytochrome P450-dependent monooxygenase system is concentrated in the endoplasmic reticulum... 

Berghout, A., Buld, J. and Wenzel, E. (1990) The cytochrome P 450 dependent monooxygenase system of the midgut of the earthworm Lumbricus terrestris. European Journal of Pharmacology, 183, 1885-1886. 

Invertebrates, toxicological effects of PCBs have been related to their ability to induce the cytochrome P450-dependent monooxygenase system (P450). This varies with the degree of chlorination and the arrangement of chlorine... 

Renton KW and Mannering GJ (1976). Depression of hepatic cytochrome P-450 dependent monooxygenase systems with administered interferon inducing agents. Biochemical and Biophysical Research Communications, 73 343-8. 

In the last two decades, microbial Cyt P450s have been studied extensively. In prokaryotes, especially Actinomycetes, Cyt P450-dependent monooxygenase systems have been known to participate in the detoxification of xenobiotics. Here the induction of Cyt P450s was also observed [12,13]. 

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