• Archives of Pharmacal Research
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• 제16권2호
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• pp.89-93
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• 1993

Incubation of $S(-)-^3H$-nicotine with rabbit lung microsomes in the presence of dioxygen and NADPH results in the formation of metabolities that bind covalently to microsomal macro-molecules. The addition of cytochrome P-450 monooxygenase inhibitors, $\alpha$-methylbenzyl ami-nobenzotriazole and aroclor 1260, inhibited both (S)-nicotine metabolism and covalent binding. The relative rates of oxidation of nicotine $\Delta^{1',5'}$ iminium ion to continine indicates that lung $100,000\times{g}$ supematant catalyzed this oxidation approximately 18 times slower than that of liver system based on mg of protein, and increased covalent interactions. Since than that of liver system based on mg of protein, nd increased covalent interactions. Since the activity of lung iminium oxidase appears much lowr than the liver, it is tempting to speculate that localized concentrations of nicotine $\Delta^{1',5'}$ iminium ion in the lung will survive for a longer period of time. These results support that cytochrome P-450 catalyzed oxidation of nicotine leads to the formation of reactive nad electrophilic intemediates capable of chemical interactions with biomacromolecules.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.149.3-150
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• 2003

CYP3A4 is the most abundant human CYP and oxidizes a diversity of substrates. including various drugs. steroids. and carcinogens. A variety of metal ions are known to affect microsomal monooxygenase activities. Effects of a series of divalent metal ions on the CYP3A4-catalyzed reaction of reconstituted system containing purified CYP3A4. NADPH-P450 reductase (NPR), and cytochrome b5 (b5) were examined. (omitted)

• Toxicological Research
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• 제5권1호
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• pp.17-25
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• 1989

Chronic adminstraction of morphine to adult male rats has long been known to lower hepatic cytochrome p-450 content and its dependent mixed-function oxidase activity. Following the treatment of adult male rats with morphine, pethidine pentazocine and codeine and also by concomitant adminstration of naloxone activities of microsomal electron transfer in the adult male rats were examined. In present study, the acute treatment of mature male rats with a dose of narcotic drugs higher than that used chronically also reduces their hepatic cytochrome p-450.

• The Korean Journal of Physiology and Pharmacology
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• 제3권2호
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• pp.207-213
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• 1999

To examine individual variation in drug metabolism catalyzed by flavin-containing monooxygenase (FMO), 179 Korean volunteers' urinary molar concentration ratio of theobromine (TB) and caffeine (CA) was determined. Their urine was collected for 1 hr (between 4 and 5 hrs) after they drank a cup of coffee containing 115 mg CA and analyzed by an HPLC system. The lowest TB/CA ratio obtained was 0.40, the highest ratio was 15.17 (38-fold difference), and the median ratio for all subjects was 1.87. The mean was 2.66 with 2.36 S.D.. In 134 nonsmokers, the mean ratio was $2.35{\pm}1.93,$ that of 51 males was $2.30{\pm}2.26$ and 83 females was $2.37{\pm}1.85,$ respectively. There was no significant gender difference in the obtained TB/CA ratio (Mann-Whitney test; p=0.518). There were no smokers among the 83 female volunteers. In the remaining 96 male subjects, the ratio obtained in 51 nonsmokers was $2.30{\pm}2.06$ and that of 45 smokers was $3.62{\pm}3.19.$ This indicated that the TB/CA ratio was increased significantly in smokers (p=0.007). However, when the TB/CA ratios (FMO activity) obtained in all 179 Korean volunteers are compared with the urinary concentration ratios of paraxanthine (PX) plus 1,7-dimethylurate (17U) to CA (CYP1A2 activity), there was a weak but significant correlation (Pearson's correlation coefficient test; $r^2=0.28,$ p＜0.0001). This indicates that, although the urinary TB/CA ratio mostly represents FMO activity, minor contribution by CYP1A2 activity cannot be ignored. In conclusion, the FMO activity measured by taking the urinary TB/CA ratio from normal healthy Korean volunteers shows marked individual variations without significant gender differences and the increased TB/CA ratio observed in cigarette smokers may have been caused by the increased CYP1A2 activity.

• Archives of Pharmacal Research
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• 제27권5호
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• pp.547-553
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• 2004

The pyrrolizidine alkaloids (PAs), contained in a number of traditional remedies in Africa and Asia, show wide variations in metabolism between animal species but little work has been done to investigate differences between animal strains. The metabolism of the PA senecionine (SN) in Fischer 344 (F344) rats has been studied in order to compare to that found in the previously investigated Sprague-Dawley (SO) rats (Drug Metab. Dispos. 17: 387, 1989). There was no difference in the formation of ($\pm$) 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP, bioactivation) by hepatic microsomes from either sex of SO and F344 rats. However, hepatic microsomes from male and female F344 rats had greater activity in the Noxidation (detoxication) of SN by 88% and 180%, respectively, when compared to that of male and female SD rats. Experiments conducted at various pH showed an optimum pH of 8.5, the optimal pH for flavin-containing monooxygenase (FMO), for SN N-oxidation by hepatic microsomes from F344 females. In F344 males, however, a bimodal pattern was obtained with activity peaks at pH 7.6 and 8.5 reflecting the possible involvement of both cytochrome P450 (CYP) and FMO. Use of specific inhibitors (SKF525A, 1-benzylimidazole and methimazole) showed that the N-oxide of SN was primarily produced by FMO in both sexes of F344 rats. In contrast, SN N-oxide formation is known to be catalyzed mainly by CYP2C11 rather than FMO in SD rats. This study, therefore, demonstrated that there were substantial differences in the formation of SN N-oxide by hepatic microsomes from F344 and SD rats and that this detoxification is catalyzed primarily by two different enzymes in the two rat strains. These findings suggest that significant variations in PA biotransformation can exist between different animal strains.

• 한국환경농학회지
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• 제41권2호
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• pp.115-124
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• 2022

BACKGROUND: Methane is a major greenhouse gas attributed to global warming partly contributed by agricultural activities from ruminant fermentation and rice paddy fields. Methanotrophs are microorganisms that utilize methane. Their unique metabolic lifestyle is enabled by enzymes known as methane monooxygenases (MMOs) catalyzing the oxidation of methane to methanol. Rice absorbs, transports, and releases methane directly from soil water to its stems and the micropores and stomata of the plant epidermis. Methylobacterium species associated with rice are dependent on their host for metabolic substrates including methane. METHODS AND RESULTS: Methylobacterium spp. isolated from rice were evaluated for methane oxidation activities and screened for the presence of sMMO mmoC genes. Qualitatively, the soluble methane monooxygenase (sMMO) activities of the selected strains of Methylobacterium spp. were confirmed by the naphthalene oxidation assay. Quantitatively, the sMMO activity ranged from 41.3 to 159.4 nmol min^-1 mg of protein^-1. PCR-based amplification and sequencing confirmed the presence and identity of 314 bp size fragment of the mmoC gene showing over 97% similarity to the CBMB27 mmoC gene indicating that Methylobacterium strains belong to a similar group. CONCLUSION(S): Selected Methylobacterium spp. contained the sMMO mmoC gene and possessed methane oxidation activity. As the putative methane oxidizing strains were isolated from rice and have PGP properties, they could be used to simultaneously reduce paddy field methane emission and promote rice growth.

• Archives of Pharmacal Research
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• 제7권1호
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• pp.53-56
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• 1984

The effect of twenty two spices on liver microsomal monooxygense activity was tested as measured by alteration of hexobarbital (HB) narcosis and strychnine mortality in mice. Oral administration of seven spices for 7 consecutive days caused a significant shortening of the duration of HB-induced sleeping time. The treatment of mice with a single i. p. injection of 9 spices resulted in a significant prolongation of the sleeping time. White pepper, dill and fennel reduced the toxicity of strychnine. These results strongly indicated that some spices might affect the activity of liver microsomal drug metabolizing enzyme (DME) function.

• Biotechnology and Bioprocess Engineering:BBE
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• 제8권5호
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• pp.309-312
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• 2003

The transformation capacity (T$\_$c/) of Methylosinus trichosporium OB3b in the degradation of ethylene chlorides was determined by measuring the decrease of soluble methane monooxygenase (sMMO) activity of resting cells in batch experiments. All measurements of sMMO activity were taken in the presence of 20 mM formate to avoid the deficiency of reducing power, and within 2 hrs to avoid the effect of natural inactivation from instability of the resting cells. The constant T$\_$c/ values of 0.58 ${\pm}$ 0.132 and 0.80 ${\pm}$ 0.17 ${\mu}$mol/mg cell were obtained for trichloroethylene (TCE) and 1,2-dichloroethylene (cis and trans-1,2-DCE), respectively, regardless of their concentrations. The transformation capacity measured by this method can be used to predict the amount of cells that should be stimulated in in-situ bioremediation.

• 생약학회지
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• 제37권2호통권145호
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• pp.97-102
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• 2006

Garlic(Allium sativum Linn) is widely used as a common condiment for a variety of foods and beverages. It has been well known that fresh garlic and garlic supplement of commercial preparations have various therapeutic properties including antimicrobial activity, antiplatelet aggregation, antihypertension, and cholesterol-lowering effects, which contribute to its increasing uses for an alternative medicine. Allicin(diallyl thiosulfinate), the major bioactive components of garlic, is formed by alliinase cleavage of the naturally occurring alliin upon crushing or mincing of garlic, and is the progenitor of a number of other products, such as diallyl disulfide. CYP3A4, heme-containing monooxygenase, is a key enzyme responsible for drug metabolism. Therefor, in the present study, we isolated and examined the compounds with CYP3A4-inhibiting activities from garlic. Among EtOAc extracts of garlic, we found that N-p-coumaroyltyramine and N-feruloyltyramine showed remarkable CYP3A4-inhibiting activities, compared to diallyl disulfide. Structures of the isolated active compounds were established by chemical and spectroscopic means.

• 한국토양환경학회지
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• 제4권1호
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• pp.13-23
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• 1999

본 연구에서는 기아상태에 있는 토양 미생물, Arthrobacter crystallopoietes cell의 2-hydroxypyridine대사능력의 변화 와 이 미생물의 대사능력에 대한 부식산의 영향에 대해 다루어졌다. 기질 2-HP에 대한 대수기 세포(exponential phase cell)는 적응기 세포(lag phase cell)와 비교할 때 기아상태에 있어서도 더 높은 2-HP대사능력을 보여 기아상태 3일 후 대수기 세포에서 2-HP반감기는 14시간으로 나타난 반면 적응기 세포의 경우 46.5시간으로 나타났다. 부식산은 기아상태에서 이 미생물 세포의 유도효소, 2-HP monooxygenase의 안정성을 높여주어 기아시간 2일 후 표준조건에서 기아상태에 있던 미생물의 효소활성이 처음의 1.5%로 남아 있는 반면 0.2% 부식산 용액에서 기아상태로 있던 미생물의 효소활성은 12%까지 남아 있었다. 기아시간 14일 후 까지도 부식산 용액 속에서 기아상태로 있던 이 미생물 세포의 2-HP대사능력은 표준 조건의 것에 비해 월등히 높아 2-HP반감기를 비교해 보면 표준 조건의 경우 43시간인 반면 부식산의 경우 1.25시간으로 나타났다.