Cytochrome P450-dependent microsomal

Ghezzi, P., Saccardo, B., and Bianchi, M. (1986a). Recombinant tumor necrosis factor depresses cytochrome P450-dependent microsomal drug metabolism in mice. Biochem. Biophys. Res. Commun. 136, 316-321. 

Analysis of reaction mixtures for 1-propanol and 2-propanol following incubation of NDPA with various rat liver fractions in the presence of an NADPH-generating system is shown in Table I ( ). Presence of microsomes leads to production of both alcohols, but there was no propanol formed with either the soluble enzyme fraction or with microsomes incubated with SKF-525A (an inhibitor of cytochrome P450-dependent oxidations). The combined yield of propanols from 280 ymoles of NDPA was 6.1 ymoles and 28.5 ymoles for the microsomal pellet and the 9000 g supernatant respectively. The difference in the ratio of 1- to 2-propanol in the two rat liver fractions may be due to differences in the chemical composition of the reaction mixtures (2) Subsequent experiments have shown that these ratios are quite reproducible. For comparison, Table I also shows formation of propanols following base catalyzed decomposition of N-propyl-N-nitrosourea. As expected (10,11), both propanol isomers were formed, the total yield in this case being almost quantitative. 

In microsomes from Sinapis alba L.,33,34 Tropaeolum majus L.,35,36 and Carica papaya L.,37 the aromatic amino acids (tyrosine and phenylalanine) have been shown to be converted to the corresponding oximes by cytochrome P450-dependent monooxygenases. The conversion of tyrosine to the corresponding oxime in microsomes from S. alba was approximately 1000 fold lower than in microsomes from the cyanogenic sorghum.33 This made a biochemical approach for the isolation... 

Jousserandot, A., Boucher, J. L., Henry, Y., Niklaus, B., Clement, B., Mansuy, D., Microsomal cytochrome P450 dependent oxidation of N-hydroxyguanidines, amidoximes, and ket oximes mechanism of the oxidative cleavage of their C=N(OH) bond with formation of nitrogen oxides, Biochemistry 37 (1998),... 

Minn AT, Pelczar H, Denizot C, Martinet M, Heydel JM, et al. 2005. Characterization of microsomal cytochrome P450-dependent monooxygenases in the rat olfactory mucosa. Drug Metab Dispos 33 1229-1237. 

Li Y, Wang E, Patten CJ, Chen L, Yang CS. Effects of flavonoids on cytochrome P450-dependent acetaminophen metabolism in rats and human liver microsomes. Drug Metab Dispos 1994 22(4) 566-571. 

Stoyanovsky, D.A. Cederbaum, A.I. (1996) Thiol oxidation and cytochrome P450-dependent metabolism of CCI4 triggers Ca2+ release from liver microsomes. Biochemistry, 35, 15839-15845... 

Suggestions about the metabolic pathway leading to " CO2 were provided by the work of Marker and Kulkami (1985, 1986). They showed that the microsomal metabolism of 2-nitropropane in mice resulted in the release of nitrite in a cytochrome P450-dependent reaction. In contrast to earlier results in rats, cnzx matic denitrification in mice did not require enzyme induction. 

Cholecalciferol 25-hydroxylase is not restricted to the liver kidneys, skin, and gut microsomes also have a cytochrome P450 -dependent enzyme that catalyzes the 25-hydroxylation of cholecalciferol and la-hydroxycholecalciferol, hut not ergocalciferol. Although there is some evidence that calcitriol can reduce the activity of calciferol 25-hydroxylase, it is not known whether this is physiologically important the major factor controlling 25-hydroxylation is the rate of uptake of cholecalciferol into the liver. It is the fate of calcidiol in the kidneys that provides the most important regulation of vitamin D metabolism (Wikvall, 2001). 

The active metabolite of vitamin D, calcitriol, is formed in the proximal tubules of the kidneys from calcidiol. There are three cytochrome P450-dependent enzymes in kidneys that catalyze 1-hydroxylation of calcidiol CYP27A and CYP27 in mitochondria and a microsomal la-hydroxylase, which is ferredoxin-dependent. It is likely that the microsomal enzyme is the most important its synthesis is induced by cAMP in response to parathyroid hormone (Section 3.2.8.2) and repressed by calcitriol (Omdahl et al., 2001 Wikvall, 2001). 

Compounds that induce cytochrome P450-dependent hydroxylases, such as barbiturates and the anticonvulsants primidone and diphenylhydantoin, cause increased output of vitamin D metabolites in the bile, and increase the rate of inactivation of calcidiol by liver microsomes. As a result of this, longterm use of these anticonvulsants may be associated with the development of... 

Vitamin E deficiency is also associated with impaired mitochondrial oxidative metabolism and impaired activity of microsomal cytochrome P450-dependent mixed-function oxidases, and hence the metabolism of xenobi-ofics. There is no evidence that vitamin E has any specific role in electron transport in mitochondria or microsomes. Again, changes in membrane lipids and oxidative damage presumably account for the observed metabolic abnormalities. 

Microsomal, cytochrome P450-dependent enz)unes isolated from the cells of E. californica convert (S)-scoulerine to (S)-stylopine by the introduction of methylenedioxy bridges (Bauer and Zenk, 1991). This conversion is catalysed by P450-dependent s)mthases (chalanthifoline and stylopine synthase) (Facchini, 2001 Ikezawa et al., 2007). The subsequent N-methylation requires... 

The second pathway for ethanol metabolism is called the ethanolinducible microsomal ethanol-oxidizing system (MEOS). This cytochrome P450-dependent pathway (Section 26.4.2) generates acetaldehyde and subsequently acetate... 

Lee CA, Lawrence BP, Kerkvliet NI, Rifkind AB. 1998. 2,3,7,8-Tetrachloro-dibenzo-p-dioxin induction of cytochrome P450-dependent arachidonic acid metabolism in mouse liver microsomes ... 

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