Abstract
Mammalian microsomal flavin-containing mono-oxygenase (FMO, EC 1.14.13.8) oxygenates a large number of heteroatom-containing xenobiotics (reviewed in Ziegler, 1988). As is the case with the other major monooxygenase system, the cytochrome P-450-dependent mixed-function oxidase, FMO is found in highest concentration in liver and requires NADPH and 02 for activity. However, unlike the P-450 system, mammalian FMO is not inducible by phenobarbital, 3-methylcholanthrene or any of the other classes of P-450 inducers. Mammalian FMO does appear to be regulated developmentally in a number of species and tissues. Examples include sex differences, and variations with age, oestrus cycle or pregnancy (Das and Ziegler, 1970; Heinze et al., 1970; Uehleke et al., 1971; Devereux and Fouts, 1974, Devereux and Fouts, 1975; Wirth and Thorgeirsson, 1978; Duffel et al, 1981; Dixit and Roche, 1984; Williams et al., 1985; Dannan et al, 1986; Tynes and Philpot, 1987). Studies employing gonadectomy of young animals indicate a role for the sex steroids in regulation of FMO (Duffel et al, 1981; Dannan et al, 1986).
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Burnette, W.N. (1981) ‘Western blotting.’ Electrophoretic transfer of proteins from sodium dodecyl sulfate-polyacrylamide gels to unmodified nitrocellulose and detection with antibody and radioiodinated Protein A. Anal. Biochem., 112, 195–203.
Dannan, G.A., Guengerich, F.P. and Waxman, D.J. (1986) Hormonal regulation of rat liver microsomal enzymes. Role of gonadal steroids in programming, maintenance, and suppression of 4-steroid 5-reductase, flavin-containing monooxygenase, and sex-specific cytochromes P-450. J. Biol. Chem., 261, 10728–35.
Das, M.L. and Ziegler, D.M. (1970) Rat liver oxidative N-dealkylase and N-oxidase activities as a function of animal age. Arch. Biochem. Biophys., 140, 300–6.
Devereux, T.R. and Fouts, J.R. (1974) N-Oxidation and demethylation of N,N- dimethylaniline by rabbit liver and lung microsomes. Effect of age and metals. Chem.-Biol. Interactions, 8, 91–105.
Devereux, T.R. and Fouts, J.R. (1975) Effect of pregnancy or treatment with certain steroids on N,N-dimethylaniline demethylation and N-oxidation by rabbit liver or lung microsomes. Drug Metab. Dispos., 3, 254–8.
Dixit, A. and Roche, T.E. (1984) Spectrophotometric assay of the flavin-containing monooxygenase and changes in its activity in female mouse liver with nutritional and diurnal conditions. Arch. Biochem. Biophys., 233, 50–63.
Duffel, M.W., Graham, J.M. and Ziegler, D.M. (1981) Changes in dimethylaniline N-oxidase activity of mouse liver and kidney induced by steroid sex hormones. Mol. Pharmacol., 19, 134–9.
Gold, M.S. and Ziegler, D.M. (1973) Dimethylaniline N-oxidase and aminopyrine N-demethylase activities of human liver tissue. Xenobiotica, 3, 179–89.
Heinze, E., Hlavica, P., Kiese, M. and Lipowsky, G. (1970) N-Oxygenation of arylamines in microsomes prepared from corpora lutea of the cycle and other tissues of the pig. Biochem. Pharmacol., 19, 641–9.
Lawton, M.P., Gasser, R., Tynes, R.E. et al. (1990) The flavin-containing monooxygenase enzymes expressed in rabbit liver and lung are products of related but distinctly different genes. J. Biol. Chem., 265, 5855–61.
Mayes, E.L.V. (1984) Peptide mapping by reverse-phase high pressure liquid chromatography, in Methods in Molecular Biology, vol. 1 Proteins (ed. J.M. Walker), Humana Press, USA, pp. 33–9.
Nagata, T., Williams, D.E. and Ziegler, D.M. (1990) Substrate specificities of rabbit lung and porcine liver flavin-containing monooxygenases: differences due to substrate size. Chem. Res. Toxicol., 3, 372–6.
Ohmiya, Y. and Mehendale, H.M. (1983) N-Oxidation of N,N-dimethylaniline in the rabbit and rat lung. Biochem. Pharmacol., 32, 1281–5.
Otvos, J.D., Krum, D.P. and Masters, B.S.S. (1986) Localization of the free radical on the flavin mononucleotide of the air-stable semiquinone state of NADPH- cytochrome P-450 reductase using 31P-NMR spectroscopy. Biochemistry, 25, 7220–8.
Poulsen, L.L. and Ziegler, D.M. (1979) The microsomal FAD-containing monooxygenase. Spectral characterization and kinetic studies. J. Biol. Chem., 254, 6449–55.
Poulsen, L.L., Taylor, K., Williams, D.E. et al. (1986) Substrate specificity of the rabbit lung flavin-containing monooxygenase for amines: oxidation products of primary alkylamines. Mol. Pharmacol., 30, 680–5.
Sotirhos, N., Herslof, B. and Kenne, L. (1986) Quantitative analysis of phospholipids by 31P-NMR. J. Lipid Res., 27, 386–92.
Tynes, R.E. and Philpot, R.M. (1987) Tissue- and species-dependent expression of multiple forms of mammalian microsomal flavin-containing monooxygenase. Mol. Pharmacol., 31, 569–74.
Tynes, R.E., Sabourin, P.J. and Hodgson, E. (1985) Identification of distinct hepatic and pulmonary forms of microsomal flavin-containing monooxygenase in the mouse and rabbit. Biochem. Biophys. Res. Commun., 126, 1069–75.
Uehleke, H., Reiner, O. and Hellmer, K.H. (1971) Perinatal development of tertiary amine N-oxidation and NADPH cytochrome c reduction in rat liver microsomes. Res. Commun. Chem. Pathol. Pharmacol., 2, 793–805.
Williams, D.E., Ziegler, D.M., Nordin, D.Jet al. (1984) Rabbit lung flavin-containing monooxygenase is immunochemically and catalytically distinct from the liver enzyme. Biochem. Biophys. Res. Commun., 125, 116–22.
Williams, D.E., Hale, S.E., Muerhoff, A.S. and Masters, B.S.S. (1985) Rabbit lung flavin-containing monooxygenase. Purification, characterization, and induction during pregnancy. Mol. Pharmacol., 28, 381–90.
Williams, D.E., Meyer, H.H. and Dutchuk, M.S. (1989) Distinct pulmonary and hepatic forms of flavin-containing monooxygenase in sheep. Comp. Biochem. Physiol., 93B,465–70.
Wirth, P.J. and Thorgeirsson, S.S. (1978) Amine oxidase in mice — sex differences and developmental aspects. Biochem. Pharmacol., 27, 601–3.
Ziegler, D.M. (1988) Flavin-containing monooxygenases: catalytic mechanism and substrate specificities. Drug Metab. Rev., 19, 1–32.
Ziegler, D.M., Taylor, K.L., Nagata, T. and Poulsen, L.L. (1986) Effects of phospholipids on activity of the purified hog liver flavin-containing monooxygenase. Fed. Proc. (abstract), 45, 1871.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1991 Springer Science+Business Media Dordrecht
About this chapter
Cite this chapter
Williams, D.E. (1991). Factors regulating the activity of the rabbit lung flavin-containing mono-oxygenase. In: Hlavica, P., Damani, L.A. (eds) N-Oxidation of Drugs. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-3112-4_6
Download citation
DOI: https://doi.org/10.1007/978-94-011-3112-4_6
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-010-5378-5
Online ISBN: 978-94-011-3112-4
eBook Packages: Springer Book Archive