• 생물정신의학
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• 제13권3호
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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.

• 한국연초학회지
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• 제20권1호
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• pp.99-107
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• 1998

Numerous studies have demonstrated a negative association between cigarette smoking and Parkinson's disease. The present study was undertaken to investigate whether chronic exposure of mice to cigarette smoke a(footed the metabolism of 1-methyl-1113,6-tetrahydro-pyridine (MPTP) by cytochrome P4SO (P-450) or flavin-containing monooxygenase (FMO) in the hepatic microsomes of C57BL6/J mice. Adult male C57BL6/J mice were exposed to mainstream smoke generated from 15 cigarettes for 10 min a day and 5 day per week for 6 weeks. MPTP (10 mg/kg body weight) was administered to mice by subcutaneous injection for 6 consecutive days. Microsolnal P-450 content was increased by MPTP, smoke exposure, or both, but NADPH cytochrome P-450 reductase activity was rather decreased by the same treatments. The activities of benzo(a)pyrene hydroxylase, 7-ethoxycoumarin O-deethylase and ethoxyresorufin O-deethylase were significantly increased by the exposure of cigarette smoke, but were not or little affected by MPTP treatment. Benzphetamine N-demethylase activity was not affected either by MPTP treatment or by cigarette smoke exposure, but it was significantly increased by the combined MPTP treatment with cigarette smoke exposure, showing their synergic effect for the induction of the enzyme activity. Interestingly, in vitro studies of hepatic FMO and P-450 system both O-oxygenation and N-demethylation of MPTP were increased in the smoke-exposed or in the MPTP-treated mice. These results suggest that the enhancement in the N-demethylation as well as O-deethylation of P-450 system and in the N-oxygenation of FMO activity by cigarette smoke exposure in mouse liver may contribute to attenuating the neurotoxic effects of MPTP on the nigrostriatal dopaminergic neurons.

• 한국식품위생안전성학회지
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• 제37권4호
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• pp.207-215
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• 2022

계란의 비린내 강도는 가금류의 종류와 개인의 인식에 따라 다르지만 여러 요인에 의해 발생할 수 있다. 특히 트리메틸아민(TMA)이 원인으로 밝혀졌다. 주목할만한 점은 리보플라빈이 TMA를 무취의 트리메틸아민-N-옥사이드로 전환시키는 역할을 하는 효소인 플라빈 함유 모노옥시게나제 3의 활성을 증가시킬 수 있다는 점이다. 본 연구는 난황의 TMA 함량을 분석하여 비린내에 대한 기여도를 평가하고, 비린내를 방지하는 방법을 개발하는 것을 목적으로 하였다. 고체상 미세추출-기체 크로마토그래피/질량 분석법을 사용하여 리보플라빈이 강화, 보충된 사료를 먹인 암탉의 난황에 있는 휘발성 화합물을 감지하고 정량화했다. 또한 샘플 간 휘발성 물질의 상대적 함량을 비교하기 위해 전자코를 이용하여 상관관계 연구를 수행하였다. TMA는 콜린이 함유된사료를 섭취한 가금류의 난황에서 고농도로 검출되었지만 리보플라빈이 보충된 사료를 섭취한 가금류에서는 검출되지 않았다. 전반적으로, 이 연구는 리보플라빈이 TMA를 포함하여 계란에 존재하는 휘발성 물질의 양과 품질에 영향을 미친다는 것을 시사한다. 이러한 발견이 계란의 비린내를 줄이는 것은 물론 품질 향상에 기여하기를 기대한다.