Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D02011 (FAD)
 5,530 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A cytosolic NADPH-dependent FAD-containing enzyme purified from Trypanosoma cruzi epimastigotes [Kuwahara, White, and Agosin: Biochem. Biophys. Res. Commun. 124, 121 (1984); Arch. Biochem. Biophys. 239, 18 (1985)] catalyzes the conversion of N,N-dimethylaniline to its corresponding N-oxide. The identity of the product has been established by high performance liquid chromatography and paper chromatography elution patterns and by electron impact spectrometry. The oxidation of N,N-dimethylaniline was determined by following the oxidation of NADPH spectrophotometrically, and a double reciprocal plot of reaction velocity vs. substrate concentration was prepared. At an optimum pH of 8.0, the plot resulted in Km and Vmax values of 56 microM and 114 nmol X min-1 X mg of protein-1, respectively. The oxidative activity of the enzyme suggests that it may be involved in detoxication processes which may contribute to the resistance of T. cruzi to known antiprotozoal drugs.
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PMID:Conversion of N,N-dimethylaniline to N,N-dimethylaniline-N-oxide by a cytosolic flavin-containing enzyme from Trypanosoma cruzi. 288 78

S- and N-Oxygenations are mostly mediated by either the cytochrome P-450 group of enzymes (haemoproteins), or the FAD-containing monooxygenases (flavoproteins). The nucleophilicity of the heteroatom may be an important determinant of which of these microsomal enzymes is utilised for specific oxygenations. This article describes the approaches that could be used for assessing the relative contribution of these microsomal oxidases to a particular reaction, with reference to studies with N,N-dimethylaniline, diethylsulphide, tetrahydrothiophen and dibenzothiophen.
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PMID:Cytochrome P-450 and FAD-monooxygenase mediated S- and N-oxygenations. 307 88

The changes in the hepatic drug metabolizing enzymes induced by the liver tumor promoter thiobenzamide (TB) were investigated. Feeding of TB to rats at a promoting regimen (1 g/kg of diet for 2 weeks) resulted in a significant decrease in the amount of liver microsomal cytochrome P-450 and of total heme. Also, the activity of cytochrome P-450 dependent monooxygenases (aminopyrine demethylase, arylhydrocarbonmonooxygenase and ethoxycoumarindeethylase) and FAD-containing monoxygenase (N,N-dimethylaniline N-oxidase and TB S-oxidase) were depressed. By contrast, phase II enzymes such as epoxide hydrase, UDP-glucuronyl transferase and GSH-transferase were significantly induced. This overall change in the drug metabolizing system was associated with tolerance of the liver towards a high necrogenic dose of TB itself as well as with an increase of mitoses and apoptosis of the hepatocytes. The findings suggest a possible relationship between this TB-induced adaptive response and the promoting activity of the compound on liver carcinogenesis.
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PMID:Changes in the rat liver drug metabolizing system during a short thiobenzamide feeding cycle. 343 87

A flavin-containing monooxygenase has been purified to apparent homogeneity from lung microsomes of pregnant rabbits and characterized with respect to a number of physical and catalytic parameters. The apparent molecular weight, as determined on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, was 59,000, and the lung microsomal flavoprotein was shown to contain 14 nmol of FAD/mg of protein. Addition of NADP+ to the oxidized flavoprotein produced a shift in the spectrum characteristic of the flavin-containing monooxygenase from porcine liver, and addition of small amounts of NADPH to the oxidized rabbit lung enzyme produced a stable spectral intermediate consistent with that of a 4a-peroxyflavin. Rabbit lung flavin-containing monooxygenase differed markedly from the porcine liver enzyme in exhibiting a broader pH optimum from 8.5-10.5, by not being inhibited by concentrations of sodium cholate as high as 1% and by withstanding, in the absence of NADPH, incubation at 45 degrees for at least 10 min with no significant loss of activity. Unlike the pig liver enzyme, purified rabbit lung enzyme was not activated by n-octylamine and, in fact, n-octylamine stimulated NADPH oxidation. A number of compounds known to be substrates of the pig liver enzyme, including benzphetamine, chlorpromazine, and imipramine, are not substrates for the rabbit lung enzyme, whereas prochlorperazine and trifluoperazine are excellent substrates. Antibodies to rabbit lung flavin-containing monooxygenase were raised in guinea pig and utilized for the immunoquantitation of this enzyme throughout gestation. The activity (as determined by N,N-dimethylaniline-N-oxidation) and amount of rabbit lung flavin-containing monooxygenase were maximally induced (5-fold) on the 28th day of gestation. Liver microsomes from rabbit did not contain any of the lung form of flavin-containing monooxygenase at any time during gestation, as evidenced by results from Western blotting. These results demonstrate that, at least in rabbit, flavin-containing monooxygenase can exist as more than a single form. The physiological significance of the induction of this enzyme during pregnancy is not known.
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PMID:Rabbit lung flavin-containing monooxygenase. Purification, characterization, and induction during pregnancy. 390 72

A microsomal flavin-containing monooxygenase (FMO) was purified 77-fold from macacque liver microsomes on the basis of its methyl p-tolyl sulfoxidase activity. Sequential chromatography on anion- and cation-exchangers, lauryl-Sepharose and 2',5'-ADP-Sepharose provided a purified preparation which exhibited an apparent molecular mass of 59 kDa and a pI of 8.3. N-terminal amino-acid sequencing revealed the characteristic Gly-X-Gly-X-X-Gly consensus sequence for the putative FAD-binding domain of microsomal FMO. In marked contrast to the well-characterized hepatic and pulmonary forms present in experimental animals, the macacque liver enzyme displayed stereoselectivity for sulfoxidation of p-tolyl methyl sulfide on the pro-S rather than the pro-R face of the substrate. Polyclonal antibodies raised against the macacque liver form exhibited little or no cross-reactivity with major purified forms of the enzyme isolated from rabbit liver, guinea-pig liver or rabbit lung. Anti-macacque liver FMO did not cross-react with human fetal liver or adult kidney microsomes, but did recognize a 59 kDa constituent of human adult liver microsomes. The intensity of this immunoreactive 59 kDa band correlated well with human liver microsomal N,N-dimethylaniline N-oxygenase activity. We conclude that human adult liver selectively expresses a microsomal FMO which is functionally and immunochemically distinct from the FMO form(s) present in human fetal liver and adult kidney, and from the major hepatic and pulmonary forms present in common laboratory animals.
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PMID:Purification of macaque liver flavin-containing monooxygenase: a form of the enzyme related immunochemically to an isozyme expressed selectively in adult human liver. 844 76