The Flavin-Containing Monooxygenase in Rat Liver: Evidence for the Expression of a Second Form Different from FMO1

Moroni, Patricia; Longin-Sauvageon, Christiane; Benoît, Etienne

doi:10.1006/bbrc.1995.2042

Cited by 21 publications

(12 citation statements)

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“…An attempt to purify FMOs from the liver of a dog was carried out. A chromatographic method, which allowed us to separate rat FMO1 from rat FMO3 (Moroni et al, 1995), did not succeed in the separation of the two antigens in the dog. The semipurified preparation obtained is recognized by these two antibodies.…”

Section: Dog Fmo1 and Fmo3mentioning

confidence: 93%

“…Purified recombinant dog FMO1 (1 g) and dog FMO3 (1 g) were detected by electrophoresis on a 10% polyacrylamide gel under denaturing conditions and stained with Coomassie blue. A mix of native dog FMO1 and dog FMO3, previously partially copurified in the laboratory from dog liver microsomes according to the method of Moroni et al (1995), were used as a control. Immunoblots were incubated for 4 h with rabbit polyclonal anti-rat FMO1 (1:1000) or anti-rat FMO-3 IgG (1:1000) (13).…”

mentioning

confidence: 99%

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Cloning, Sequencing, and Tissue-Dependent Expression of Flavin-Containing Monooxygenase (FMO) 1 and FMO3 in the Dog

Lattard

Longin-Sauvageon²,

Lachuer³

et al. 2002

Drug Metab Dispos

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This paper is available online at http://dmd.aspetjournals.org ABSTRACT:The expression of flavin-containing monooxygenases (FMOs) in dog liver microsomes was suggested by a high methimazole Soxidase activity. When the reaction was catalyzed by dog liver microsomes, apparent V max and K m values were 6.3 nmol/min/mg and 14 M, respectively. This reaction was highly inhibited (73%) in the presence of imipramine, but it was also weakly affected by trimethylamine, suggesting the involvement of different isoforms.

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Section: Dog Fmo1 and Fmo3mentioning

confidence: 93%

mentioning

confidence: 99%

Cloning, Sequencing, and Tissue-Dependent Expression of Flavin-Containing Monooxygenase (FMO) 1 and FMO3 in the Dog

Lattard

Longin-Sauvageon²,

Lachuer³

et al. 2002

Drug Metab Dispos

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“…Microsomes were prepared from rat liver, lung, kidney, brain, intestine, and uterus samples by differential centrifugation as described previously (Moroni et al, 1995). Proteins concentrations were determined by the method of Bradford (1976) using serum bovine albumin as a standard.…”

Section: Methodsmentioning

confidence: 99%

Cloning, Sequencing and Tissue Distribution of Rat Flavin-Containing Monooxygenase 4: Two Different Forms Are Produced by Tissue-Specific Alternative Splicing

Lattard¹,

Longin-Sauvageon²,

Benoît³

2003

Mol Pharmacol

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The nucleotide sequence of rat flavin-containing monooxygenase 4 (FMO4) mRNA was obtained by reverse transcriptionpolymerase chain reaction (RT-PCR) and 5Ј/3Ј terminal extension. Complete cDNA was amplified, cloned, and sequenced from the mRNA obtained from rat kidney and brain. Two different transcripts (short and long) stemming from the splicing of an internal region of 189 bases pair, corresponding to exon 4 were identified. This alternative splicing seems to be specific of the brain. The long cDNA encodes a protein of 560 amino acids with a predicted molecular mass of 63,395 Da. The short cDNA encodes a protein of 497 amino acids with a predicted molecular mass of 55,871 Da. Both of these encoded sequences contain the NADPH-and FAD-binding sites and a hydrophilic carboxyl terminus. These sequences are 80 and 79% identical to the sequences of human and rabbit FMO4. By Northern blotting and/or RT-PCR, the long-form FMO4 mRNA was detected in the rat kidney, intestine, and liver and the short form particularly in the brain. For the first time, the expression of FMO4 protein was demonstrated. By Western blotting using the two different forms of FMO4 antibodies, a long FMO4 protein was detected in the rat kidney, whereas in the rat brain, only the short form of FMO4 was observed.

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“…The kinetic patterns in rat and human liver microsomes were shown to be similar to those with FMO1 and FMO3, respectively. Thus, the rat liver microsomes showed a higher metabolic rate for the DMANO formation than the human liver microsomes because FMO1 exists predominantly in rat liver microsomes, whereas FMO3 exists predominantly and only a trace content of FMO1 (less than 0.2% of total FMO) is found in human liver microsomes (Moroni et al 1995;Cashman & Zhang 2006).…”

Section: Kinetic Study For the Dmano Formation From Dmamentioning

confidence: 95%

Flavin-containing monooxygenase 1-catalysedN,N-dimethylamphetamineN-oxidation

et al. 2009

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N,N-dimethylamphetamine (DMA) is a methamphetamine analogue known to be a weaker central nervous system stimulant than methamphetamine. Although a major metabolite of DMA is known to be DMA N-oxide (DMANO), which may be catalysed by flavin-containing monooxygenase (FMO), the specific enzyme(s) involved in this biotransformation has not been identified. In this study, the specific enzyme(s) involved with DMA N-oxidation was characterized by several assays. When DMA was incubated with different human recombinant drug-metabolizing enzymes, including FMOs and cytochrome P450s (CYPs), the formation of DMANO by FMO1 was the most predominant. The Michaelis-Menten kinetic constants for DMA N-oxidation by FMO1 were: K(m) of 44.5 microM, V(max) of 7.59 nmol min(-1) mg(-1) protein, and intrinsic clearance of 171 microl min(-1) mg(-1) protein, which was about twelve-fold higher than that by FMO3. Imipramine, an FMO1-specific inhibitor, selectively inhibited DMA N-oxidation. The resulting data showed that DMA N-oxidation is mainly mediated by FMO1.

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The Flavin-Containing Monooxygenase in Rat Liver: Evidence for the Expression of a Second Form Different from FMO1

Cited by 21 publications

References 0 publications

Cloning, Sequencing, and Tissue-Dependent Expression of Flavin-Containing Monooxygenase (FMO) 1 and FMO3 in the Dog

Cloning, Sequencing, and Tissue-Dependent Expression of Flavin-Containing Monooxygenase (FMO) 1 and FMO3 in the Dog

Cloning, Sequencing and Tissue Distribution of Rat Flavin-Containing Monooxygenase 4: Two Different Forms Are Produced by Tissue-Specific Alternative Splicing

Flavin-containing monooxygenase 1-catalysedN,N-dimethylamphetamineN-oxidation

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