• Title/Summary/Keyword: epoxide

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The Effect of Dehydronifedipine on the Oxidation of Aflatoxin $B_1$ by Cytochrome P450 3A4 (Cytochrome P450 3A4에 의한 Aflatoxin $B_1$의 산화에 대한 Dehydronifedipine의 영향)

  • 김복량;권강범;김동현
    • Toxicological Research
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    • v.15 no.1
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    • pp.95-101
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    • 1999
  • Cytochrome P450 (CYP) 3A4 metabolizes aflatoxin B1 (AFB1) to AFB1-exo-8,9-epoxide (8,9-epoxidation) and aflatoxin Q1 (AFQ1; 3$\alpha$-hydroxylation) simultaneously. We investigated whether each metabolite was formed via its own binding site of CAP3A4 active site. Kinetics of the formation of the two metabolites were sigmoidal and consistent with the kinetics of substrate activation. The HIll model predicted that two substrate binding wites are involved in the oxidationof AFB1 by CYP3A4. Dehydronifedipine, a metabolite of nifedipine generated by CYP3A4, inhibited the formation of AFQ1 without any inhibition in the formation of AFB1-exo-8,9-epoxidation. Dehydronifedipine was found to act as a reversible competitive inhibitor against 3$\alpha$-hydroxylation of AFB1. Vmax and S0.5 of the 8,9-epoxidation were not changed in the presence of 0, 50, or 100 $\mu\textrm{M}$ dehydronifedipine. S0.5 of 3$\alpha$-hydroxylation was increased from 58$\pm$4 $\mu\textrm{M}$ to 111$\pm$8 $\mu\textrm{M}$ in the presence of 100 $\mu\textrm{M}$ nifedipine whereas Vmax was not changed. These results suggest that there exist two independent binding sites in the active site of CAP3A4 . One binding site is responsible for AFB1-exo-8,9-epoxidation and the other is involved in 3$\alpha$-hydroxylation of AFB1. Dehydronifedipine might selectively bind to the site which is responsible for the formation of AFQ1 in the active site of CYP3A4.

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Functional Studies of Tyrosine 108 Residue in the Active Site of Human Glutathione S-Transferase P1-1

  • Park, Hee-Joong;Koh, Jong-Uk;Ahn, So-Youn;Kong, Kwang-Hoon
    • Bulletin of the Korean Chemical Society
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    • v.26 no.3
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    • pp.433-439
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    • 2005
  • To gain further insight on the relationship between structure and functions of glutathione S-transferase (GST), the three tyrosine 108 mutants, Y108A, Y108F, and Y108W, of human GST P1-1 were expressed in Escherichia coli and purified to electrophoretic homogeneity by affinity chromatography on immobilized GSH. The substitution of Tyr 108 with alanine resulted in significant decrease of the GSH-conjugation activity and the GSH peroxidase activity, but approximately 63% increase of steroid isomerase activity toward ${\Delta}^5$–[androstene 3,17-dione. On the other hand, the substitution of Tyr 108 with phenylalanine resulted in decreases of $k_{cat}\;and\;k_{cat}/K_m{^{EPNP}}$ by 2 orders of magnitude, suggesting that Tyr 108 residue of hGSTP1-1 are considered to be important for the catalysis and the binding of the epoxide substrates. The substitution of Tyr 108 with tryptophan resulted in significant decreases of the specific activities toward EPNP, cumene hydroperoxide and ${\Delta}^5$–ndrostene 3,17-dione, but approximately 2-fold increase on the enzyme-catalyzed addition of GSH to DCNB. We conclude from these results that Tyr 108 in hGST P1-1 plays very different roles depending upon the nature of the electrophilic substrates.

Distribution Profile of Chiral Organochlorine Pesticides in Ambient Air (대기 환경 중 키랄 유기염소계 농약의 분포 특성)

  • Choi, Jong-Woo;Kim, Kum-Hee;Hwang, Seung-Ryul;Lee, Kyu-Seung
    • Korean Journal of Environmental Agriculture
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    • v.31 no.3
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    • pp.255-263
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    • 2012
  • BACKGROUND: The analysis for the concentration and enantiomeric ratio of OCPs have been performed to confirm the distribution and to emonstrate the pollution characteristics of chiral OCPs in ambient air. METHODS AND RESULTS: In ambient air at coastal and inland sites, concentrations and enantiomer fractions (EFs) of heptachlor (HEPT), eptachlor epoxide (HEPX), trans-chlordane (TC), cis-chlordane (CC), xychlordane (OXY), 2,4'-DDT, 2,4'-DDD with HRGC/HRMS were investigated to understand source and distribution of chiral organochlorine pesticides (OCPs) in ambient air. The mean concentrations of OCPs in ambient air were at the range of 0.027(heptachlor)~1.279 (4,4'-DDT) pg/m3 and 0.0005 (heptachlor)~0.1043 ng/g d.w. (TC), respectively. The mean EFs of OCPs in ambient air were at the range of 0.73 (HEPX)~0.45 (CC). Both preferential depletions of (+) and (-) enantiomer were observed for CC, indicated by EFs either <0.5 or >0.5, while preferential depletions of (-) enantiomer which mean EFs <0.5 were observed for chiral OCPs except TC and MC-5. CONCLUSION: OCPs in ambient air have been distributed from soil, but some of them such as chlordane, DDT etc. might have been introduced by long-range atmospheric transport, considering EFs by chiral analysis and trajectory analysis.

The Quantitative Changes of Major Compounds from Aster koraiensis Nakai Essential Oil by Harvesting Time (수확 시기에 따른 벌개미취 정유의 주요 화합물 함량 변화)

  • Choi, Hyang-Sook
    • The Korean Journal of Food And Nutrition
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    • v.27 no.2
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    • pp.194-202
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    • 2014
  • This study investigates the chemical compositions of Aster koraiensis Nakai essential oils and the quantitative changes of major terpene compounds according to various harvesting times. The essential oils obtained by hydrodistillation from the aerial parts of Aster koraiensis Nakai are being analyzed by GC and GC-MS. The essential oil compositions of Aster koraiensis Nakai are characterized byhigher contents of sesquiterpene compounds. Ninety-seven volatile flavor compounds are being identified in the essential oils from Aster koraiensis Nakai harvested in 2010, and caryophyllene oxide (8.38%), aristolene (7.08%), epiglobulol (5.57%), and ethyl furanone (4.73%) are the most abundant compounds. Ninety-five compounds are identified in the essential oils from the plants harvested in 2011, and aristolene (11.56%), calarene (9.33%), phytol (8.28%), ethyl furanone (7.63%), and epiglobulol (7.18%) are the most abundant compounds. Ninety-five compounds are being identified in the essential oils from the plants harvested in 2012, and calarene (15.3%), aristolene (14.24%), ethyl furanone (7.21%), phytol (6.98%) are the major compounds. The contents of aristolene, ${\alpha}$-caryophyllene, ${\alpha}$-muurolene, ${\alpha}$-calacorene, aromadendrene oxide, and calarene increase significantly from 2010 to 2012. The contents of ${\alpha}$-cubebene, isocaryophyllene, and diepi-${\alpha}$-cedrene epoxide decrease significantly from 2010 to 2012. The quantitative changes of aristolene and calarene according to harvesting time can be served as a quality index of the Aster koraiensis Nakai essential oils.

Association of Persistent Organic Pollutants (POPs) with Age and Body Mass Index in Korean Adults (한국 성인의 혈청 잔류성 유기오염물질 농도와 연령 및 체질량지수와의 관련성)

  • Moon, Ho Jung;Lim, Jung-Eun;Jee, Sun Ha
    • Journal of Environmental Health Sciences
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    • v.40 no.6
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    • pp.442-453
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    • 2014
  • Objectives: Persistent organic pollutants (POPs) are known to be the detrimental chemicals in the body, even at low levels, and are stored in adipose tissue. Recently, POPs have been reported to be associated with chronic diseases, including cancer and cardiovascular disease, and aging and obesity are reported as common factors in chronic disease. However, there have been only a few studies on the associations of POPs with age and body mass index (BMI) in Korea. Therefore, we analyzed the associations of serum POPs levels with age and BMI in Korea. Methods: This cross-sectional study includes 444 subjects (253 men and 191 women) from the Korean Cancer Prevention Study-II (2004-2011). Serum levels of 33 polychlorinated biphenyls (PCBs) and 19 organochlorine pesticides (OCPs) were measured by a gas chromatographer (Agilent 6890) coupled to high resolution mass spectrometer (JEOL JMS-800D). Results: Concentrations of PCB 153 (men: 12.26 ng/g lipid, women: 10.50 ng/g lipid) and p,p'-DDE (men: 94.66 ng/g lipid, women: 96.66 ng/g lipid) were the highest among serum PCBs and OCPs, respectively. PCBs and OCPs were significantly positively correlated with age in both sexes. After adjustment for age, non-dioxin like PCBs were significantly negatively correlated with body mass in women. However, cis-heptachlor epoxide was significantly positively correlated with body mass index in both sexes. When analyzed by sex, stronger associations were shown between POPs and age in men and POPs and BMI in women. Conclusion: These results may provide baseline data for the study of POPs and for the health management field in Korea.

Tuning Exothermic Curing Reaction of Hydrogenated Bisphenol A Epoxy Resins for Stone Conservation (석조문화재 보존.복원에 적용될 에폭시 수지의 경화 시 반응열 제어 및 안정성 향상 연구)

  • Choi, Yong-Seok;Park, You-Jin;Kang, Yong-Soo;Won, Jong-Ok;Kim, Jeong-Jin;Kim, Sa-Dug
    • Journal of Conservation Science
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    • v.28 no.2
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    • pp.131-139
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    • 2012
  • The exothermic cure kinetics of epoxy resin was controlled by hardener containing fast and slow curing agents. The epoxy risen comprises hydrogenated bisphenol A-based epoxide (HBA), fast curing agent (FH) and slow curing agent poly(propyleneglycol)bis(2-aminopropylether) (SH). Talc was used as an inorganic additive. In the process of curing, cure kinetics along with temperature was monitored by differential scanning calorimeter (DSC) and thermocouple to show that the temperature increase was well controlled by adjusting the hardener mixture. Additionally, bending and tensile strengths of the epoxy/talc composites were also measured to be lower and higher with the amount of the talc inorganic additive, respectively. It is thus concluded that the increase in the temperature during exothermic curing reaction and mechanical properties of epoxy resins are tuned by optimizing hardener mixture for successful stone conservation.

Synthesis of Optically pure Epichlorohydrine using Dimeric Chiral Salen Catalyst Containing BF3 (BF3 함유 이분자형 키랄 살렌 촉매에 의한 고광학순도의 에피클로로히드린 합성)

  • Lee, Kwang-Yeon;Rahul, B. Kawthekar;Kim, Geon-Joong
    • Applied Chemistry for Engineering
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    • v.18 no.4
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    • pp.330-336
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    • 2007
  • In this study, new dinuclear chiral Co (salen) complexes bearing $BF_3$ have been synthesized and their properties as the asymmetric catalyst have been examined. The NMR, UV and ESCA analyses were performed to determine the structure of synthesized catalysts. Their catalytic activity and selectivity have been demonstrated for the asymmetric ring opening of various terminal epoxides by hydrolytic kinetic resolution technology. The easily prepared dimeric complexes exhibited very high enantioselectivity for the asymmetric ring opening of epoxides with $H_2O$ nucleophile, providing enantiomerically enriched terminal epoxides (> 99 %ee). The dimeric structured chiral salen showed remakablely enhanced reactivity and may be employed substantially lower loadings than its monomeric analogues, and in addition no racemization happened during the separation of product epoxides. The system described in this work is very efficient for the sinthesis of chiral epoxide and 1,2-diol intermediates.

Influence of Cooking, Storage Period, and Re-heating on Production of Cholesterol Oxides in Chicken Meat

  • Choe, Juhui;Min, Joong-Seok;Lee, Sang-Ok;Khan, Muhammad Issa;Yim, Dong Gyun;Lee, Mooha;Jo, Cheorun
    • Food Science of Animal Resources
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    • v.38 no.3
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    • pp.433-441
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    • 2018
  • The objective of present study was to investigate the effect of cooking and their combinations with re-heating methods on the formation of cholesterol oxidation products (COPs) in stored chicken thigh meat. Pan roasting, steaming, oven grilling, charcoal grilling, and microwaving were used for cooking. Re-heating of samples was done using the same cooking methods or microwaving after 3 and 6 d of refrigerated storage. Cooking and re-heating resulted in reduction of crude fat and cholesterol contents of chicken thigh meat depending on storage period before re-heating. Cooking and storage period had no influence on the total amount of COPs. The highest total amount of COPs was observed in meat samples cooked by steaming and reheated by microwaving after 6 d of storage, which showed similar value to raw chicken meat stored for 6 days. However, different re-heating methods formed different types of COPs depending on storage period before re-heating. The high amount (p<0.05) of 25-hydroxycholesterol or ${\alpha}-epoxide$ was detected in meat samples reheated by steaming or microwaving at 3 or 6 d of storage after steamed cooking, respectively. As a result, the combination of steaming and re-heating with microwaving could increase the total amount of COPs in chicken thigh meat and different cooking/re-heating methods could form different types of COPs, even though no significant difference in the total amount of COPs depending on storage period.

Effects of Ethanol on the Activities and Inducibility of Trichloroethylene Metabolic Enzyme System in Rat Liver (Ethanol이 Trichloroethylene 대사효소의 활성도와 유도성에 미치는 영향)

  • Kim, Ki-Woong;Kang, Seung-Kyu;Cho, Young-Sook;Lee, Sei-Hui;Moon, Young-Hahn;Choi, Byung-Soon;Park, Sang-Shin
    • Journal of Preventive Medicine and Public Health
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    • v.28 no.1 s.49
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    • pp.141-152
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    • 1995
  • This study was performed to find out the influences of ethanol on the metabolism of trichloroethylene(TRI) in rats. TRI in corn oil at the dosage of 150, 300, 600 mg/kg was injected peritoneally once a day for two days to two groups. In one group ethanol(4 g/kg) was taken orally 30 minutes before TRI injection, and the other group ethanol was not. The results of experiments are as follows: 1. The contents of cytochrome P-450 and $b_5$ had inverse relationship with in-jected TRI amounts in both groups. 2. The activity of NADPH P-450 reductase was decreased slowly in TRI injected group related with TRI amount, but decreased drastically in the group pretreated with ethanol. 3. The activity of NADH $b_5$ reductase had relationship with injected nt amount , but the statistical significance was found only in the groups of 300 and 600 mg/kg of TRI injected without relevance to ethanol when compared with the group that was not injected. 4. The activity of ADH was more decreased and ALDH activity was more increased in groups that TRI injected and ethanol was pretreated with ethanol groups than in group without any treatment. These results suggest that ethanol may inhibit epoxide formulation, the first step of TRI metabolism, and change from TCE-OH to TCA also.

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MODULATION OF TOXICITY AND CARCINOGENESIS BY CALORIC RESTRICTION

  • Allaben, William T.;Chou, Ming W.;Pegram, Rex A.;Leakey, Julian;Feuers, Ritchie J.;Duffy, Peter H.;Turturro, Angelo;Hart, Ronald W.
    • Toxicological Research
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    • v.6 no.2
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    • pp.167-182
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    • 1990
  • Dietary restriction (caloric restriction) is the only intervention which has been reliably shown to extend the maximum life span of warm-blooded animals and delay the many phenomena associated with aging. It is also one of the most effective modulators of toxicity, especially cancer endpoints. In spite of the known modulator effects of caloric restriction, the biological mechanisms responsible for these effects had not been in vestigated until recently. The National Center for Toxicological Research (NCTR), in a collaborative effort with the National Institute of Aging (NIA), initiated a project whereby nine (9) combinations of rodent species/strains and diets were fed both restricted and ad libitum. The NIA's initiative was to identify biomarkers of aging whereas NCTR's initiative was to identify the biological effects associated with the profound effects caloric restriction has in protecting against both spontaneous (age-related) and chemically-induced toxic endpoints. Independent of sex or species, caloric restriction has similar effects on body temperature, oxygen consumption and $CO_2$production. Caloric restriction also decreased lipid glycolysis and metabolism in rats and mice, which suggest decreased production of metabolites which could lead to fatty acid epoxide formation. The age-associated loss of ciradian regulation of intermediate enzymes is also significantly reduced. Moreover, caloric restriction reduced the age-associated feminization of sexually dimorphic liver isozymes, increased several glucocorticoid responsive isozymes, elevated glucagon/insulin ratios, produced less microsomal superoxide and enhanced the capacity for utilzing detoxicating metabolic pathways. Calorically restricted rats have less than half the number of aflatoxin ($AFB_1$)-DNA adducts than ad libitum animals and urinary excretion of $AFB_1$ was increased significantly. Finally, DNA repair mechanisms are enhanced and oncogene expression is decreased in calorically restricted animals.

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