• Toxicological Research
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• v.17
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• pp.127-133
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• 2001

Together with cytochrome P450 (CYP), flavin-containing monooxygenase (FMO) present in liver microsomes oxidizes various endogenous and exogenous chemicals. In an effort to determine the human FMO activity, we have developed two non-invasive urine analysis methods using caffeine (CA) and ranitidine (RA) as the probe compounds. As the production of theobromine (TB) and ranitidine N-oxide (RANO) from CA and RA is catalyzed primarily by the hepatic FMO, we have assigned the urinary molar ratios of TB/CA and RA/RANO as the in vivo FMO activity. In 200 age-matched Korean volunteers, the obtained TB/CA ratio ranged from 0.4 to 15.2 (38-fold difference) and the RA/RANO ratio from 5.7 to 27.2 (4.8-fold). The FMO activity of 20's, determined by caffeine metabolism, was the highest (2.5$\pm$l.9) and those of 30's, 40's, 50's, 60's and 70's were 40%, 50%, 24%, 39% and 36% of the 20's, respectively. Intake of grapefruit juice, known to contain flavonoids, inhibited the in vivo FMO (TB/CA) activity by 79%. Addition of the flavonoids like naringin, quercitrin and kaempferol, present in grapefruit juice, to the in vitro microso-mal FMO assay, thiobenzamide S-oxidation, produced 75%, 70% and 60% inhibition, respectively. Obtained Ki values of quercitrin, kaempferol and naringin on the in vitro FMO activity were 6.2, 12.0 and 13.9 $\mu\textrm{M}$, respectively. This suggested that the dose of drug should need to be adjusted to suit the individual FMO activities when the drugs metabolized by FMO are given to patients. As the intake of grapefruit juice has been identified to inhibit the FMO as well as CYP3A4 and lA2 activities, patients taking drugs metabolized by these enzymes should not drink grapefruit juice as the carrier.

• Environmental Analysis Health and Toxicology
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• v.15 no.4
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• pp.139-145
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• 2000

The Flavin-containing monooxygenase (FMOs) (EC1.14.13.8) are NADPH-dependent flavoenzymes that catalyze oxidation of soft nucleophilic heteroatom centers in a range of structurally diverse compounds, including foods, drugs, pesticides, and other xenobiotics. In humans, FMO3 is quantitatively a major human liver monooxygenase. In the present study, the baculovirus expression vector system was used to overexpress human FMO3 in insect cells for catalytic studies. Six commercially available organic selenium compounds were examined for substrate activity with microsomes isolated from Spodoptera frugiperda (Sf)9 cells infected with human FMO3 recombinant baculovirus. While none of the aromatic heterocyclic selenides tested showed detectable activity, all dialkyl- and alkylaryl-selenides free from ionic groups catalyzed the NADPH- and O$_2$-dependent oxidation. Kinetic constants demonstrate that (based on Km) dialkyl-and alkylaryl- selenides are better substrates for human FMO3 than analogous nitrogen or sulfur compounds .

• Environmental Analysis Health and Toxicology
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• v.16 no.2
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• pp.97-102
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• 2001

The flavin-containing monooxygenases(FMOs) (EC1.14.13.8) are NADPH0dependent flavoenzymes that catalyze oxidation of soft nucleophilic heteroatom centers in a range of structurally diverse compounds, including foods, drugs, pesticides, and other xenobiotics. In humans, FMO3 is quantitatively a major human liver monooxygenase. In the present study, the baculovirus expression vector system was used to overexpress human FMO3 in sect cells for stalytic studies. Microsomes isolated from Spodoptera frugiperda(Sf)9 cells infected with human FMO3 recombinant baculovirus catalyzed the NADPH-and O$_2$-dependent oxidation of methimazole, thiourea, and phenylthiourea. However there was no detectable activity with 1, 3-diphenylthiourea or larger thiocarbamides. Microsomes from control Sf9 cells were devoid of methimazole or thiourea S-oxygenase activity. 1, 3-diphenylthiourea is apparently completely excluded from the catalytic site, these amines drugs are probably approaching the upper size limits of xenobiotics accepted by human FMO3. The substrate specificity of this iosform in humans appears considerably more restriceted than that of pig, guinea pig, rat or rabbit FMO3.

• Interdisciplinary Bio Central
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• v.2 no.2
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• pp.6.1-6.5
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• 2010

Fragment molecular orbital (FMO) method provides a novel tool for ab initio calculations of large biomolecules. This method overcomes the size limitation difficulties in conventional molecular orbital methods and has several advantages compared to classical force field approaches. While there are many features in this method, we here focus on explaining the issues related to protein-ligand binding: FMO method provides useful interaction-analysis tools such as IFIE, CAFI and FILM. FMO calculations can provide not only binding energies, which are well correlated with experimental binding affinity, but also QSAR descriptors. In addition, FMO-derived charges improve the descriptions of electrostatic properties and the correlations between docking scores and experimental binding affinities. These calculations can be performed by the ABINIT-MPX program and the calculation results can be visualized by its proper BioStation Viewer. The acceleration of FMO calculations on various computer facilities is ongoing, and we are also developing methods to deal with cytochrome P450, which belongs to the family of drug metabolic enzymes.

• Clinical and Experimental Pediatrics
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• v.60 no.3
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• pp.94-97
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• 2017

Trimethylaminuria (TMAuria), known as "fish odor syndrome," is a congenital metabolic disorder characterized by an odor resembling that of rotting fish. This odor is caused by the secretion of trimethylamine (TMA) in the breath, sweat, and body secretions and the excretion of TMA along with urine. TMAuria is an autosomal recessive disorder caused by mutations in flavin-containing monooxygenase 3 (FMO3). Most TMAuria cases are caused by missense mutations, but nonsense mutations have also been reported in these cases. Here, we describe the identification of a novel FMO3 gene mutation in a patient with TMAuria and her family. A 3-year-old girl presented with a strong corporal odor after ingesting fish. Genomic DNA sequence analysis revealed that she had compound heterozygous FMO3 mutations; One mutation was the missense mutation p.Val158Ile in exon 3, and the other was a novel nonsense mutation, p.Ser364X, in exon 7 of the FMO3 gene. Familial genetic analyses showed that the p.Val158Ile mutation was derived from the same allele in the father, and the p.Ser364X mutation was derived from the mother. This is the first description of the p.Ser364X mutation, and the first report of a Korean patient with TMAuria caused by novel compound heterozygous mutations.

• The Journal of Korean Institute of Communications and Information Sciences
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• v.31 no.5C
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• pp.490-496
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• 2006

H.264 is the most recent video coding standard, containing improved error resilience tools than previous video compression schemes. This paper shows an analysis of the dependency of error concealment (EC) performance on the expected number of correctly received neighboring macroblock(MB)s for a lost MB, applying error concealment schemes to the raster scan mode that is used in the previous video coding standard and the flexible macroblock ordering (FMO) which is one of error-resilience tools in H.264. We also present simulation results and performance evaluation with various packet loss rates. Simulation results show that the FMO mode provides better EC performances of $1{\sim}9dB$ PSNR improvements compared to the raster scan mode because of larger expected number of correctly received neighboring MBs. The PSNR improvement by FMO mode becomes higher as the intra-frame period is larger and the packet loss rate is higher.

• Proceedings of the IEEK Conference
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• 2007.07a
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• pp.321-322
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• 2007

When use FMO by error resilience purpose in existing $TYPE1{\sim}2$ compare. But, in This paper, TYPE $3{\sim}5$[Gradual decoder refresh tool] is used as error resilence tool. Experiment result, it shows that Y PSNR improves that use suitable TYPE's FMO. Images using in an experiment had better use Type $3{\sim}5$. Differ with existing paper, dipersed mode appeared result badly. Because spatial correlation is low, acted adversely in intra predication.

• Korean Journal of Biological Psychiatry
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• v.13 no.3
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• pp.152-161
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• 2006

Objective : The relationship between the total daily dose of clozapine given and the plasma concentrations of clozapine and its metabolites(N-desmethylclozapine and clozapine N-oxide) and the effect of Glu158Lys (wild-type : Glu, 'H' ; variant : Lys, 'h') and Glu308Gly(wild-type : Glu, 'D' ; variant : Lys, 'd') variation in FMO3 gene on plasma concentrations of clozapine and its metabolites was studied in schizophrenic patients. Methods : Trough plasma concentrations of clozapine and its metabolites were measured in 34 schizophrenic patients receiving clozapine. The genetic variation of 'h' and 'd' in FMO3 were analyzed in 21 among 34 patients. Results : A linear relationship between the total daily dose of clozapine given(mg/kg body weight per day) and the plasma concentrations(nM) of clozapine was revealed by regression analysis(p<0.001) in the 23 patients receiving a constant daily dose of clozapine for 8 days. The plasma molar concentration ratios of clozapine N-oxide/clozapine in 8 subjects with 'hh' or 'Hh' alleles were not different from those in 6 subjects with 'HH' alleles and the plasma molar concentration ratios in 6 subjects with 'dd' or 'Dd' alleles were not different from those in 8 subjects with 'DD' alleles. Conclusion : The effect of Glu158Lys and Glu308Gly variation in FMO3 gene on clozapine metabolism could not be shown.

• Analytical Science and Technology
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• v.20 no.4
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• pp.339-346
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• 2007

To search the ninhydrin derivatives that have high chromogenic and fluorogenic properties, molecular holographic quantitative structure property relationship (HQSPR) models on the reactivity between glycine and ninhydrin analogues as latent fingerprint detector were derived and investigated quantitatively. The ${\varepsilon}LUMO$ (e.v.) energy of ninhydrin molecule was an important factor to reactivity of ninhydrin. And, it is suggested that the nucleophilic reaction by orbital-controlled reaction from the frontier molecular orbital (FMO) interaction between glycine and ninhydrin derivatives was more superior than that of electrophilic reaction by charged controlled reaction. The analytical results in atomic contribution maps also shows that the reactivity of ninhydrin was increased by meta-substituents as strong electron withdrawing groups on the benzo ring. Therefore, it is sugested by HQSPR and QSPR model that the 5,6-dinitroninhydrin molecule would increase the reactivity as much as three times as compared to none substituted ninhydrin molecule.

• Korean Journal of Microbiology
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• v.41 no.1
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• pp.1-7
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• 2005

Methylophaga aminosulfidovorans SK1 (KCTC 10323 BP) can utilize trimethylamine as a sole carbon, nitrogen, and energy source. The bacterial flavin-containing monooxygenase (bFMO) gene was identified in the strain and the recombinant enzyme expressed in E. coli oxidized trimethylamine. To study the function and regulation of the bfmo, over 8,000 nucleotide sequences of the neighboring regions including the bfmo were determined. Three open reading frames proceeding to the bfmo gene encoded analogues to highly conserved nitrate/nitrite sensing two-component system regulators and a methyl accepting protein. Two small open reading frames just downstream of the bfmo gene showed no similar proteins of known functions but the sequences were conserved among other bacteria. Reverse transcription-polymerase chain reaction analysis showed that the six putative genes consisted of three transcription units. The three regulatory genes located upstream of the bfmo gene formed two separate transcription units. The bfmo and the two downstream genes were transcribed from a single promoter.