• Title/Summary/Keyword: P450 1A2

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Domain Characterization of Cyclosporin Regio-Specific Hydroxylases in Rare Actinomycetes

  • Woo, Min-Woo;Lee, Bo-Ram;Nah, Hee-Ju;Choi, Si-Sun;Li, Shengying;Kim, Eung-Soo
    • Journal of Microbiology and Biotechnology
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    • v.25 no.10
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    • pp.1634-1639
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    • 2015
  • Cytochrome P450 hydroxylase (CYP) in actinomycetes plays an important role in the biosynthesis and bioconversion of various secondary metabolites. Two unique CYPs named CYP-sb21 and CYP-pa1, which were identified from Sebekia benihana and Pseudonocardia autotrophica, respectively, were proven to transfer a hydroxyl group at the 4th or 9th N-methyl leucine position of immunosuppressive agent cyclosporin A (CsA). Interestingly, these two homologous CYPs showed different CsA regio-selectivities. CYP-sb21 exhibited preferential hydroxylation activity at the 4th position over the 9th position, whereas CYP-pa1 showed the opposite preference. To narrow down the CYP domain critical for CsA regio-selectivity, each CYP was divided into four domains, and each domain was swapped with its counterpart from the other CYP. A total of 18 hybrid CYPs were then individually tested for CsA regio-selectivity. Although most of the hybrid CYPs failed to exhibit a significant change in regio-selectivity in the context of CsA hydroxylation, hybrid CYP-pa1 swapped with the second domain of CYP-sb21 showed a higher preference for the 9th position. Moreover, hybrid CYPsb21 containing seven amino acids from the 2nd domain of CYP-pa1 showed higher preference for the 4th position. These results imply that the 2nd domain of CsA-specific CYP plays a critical role in CsA regio-selectivity, thereby setting the stage for biotechnological application of CsA regio-selective hydroxylation.

CJ-11668, a new selective and potent cox-2 inhibitor, has long-acting pharmacokinetic profiles

  • Park, Hyun-Jung;Kang, Hye-Jung;Chung, Young-Mee;Chun, Hyung-Ok;Hong, Kwang-Hee;Kim, Il-Hwan;Kim, Taek-Rho;Noh, Hyun-Jung;Kim, Deog-Yeor
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.88.1-88.1
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    • 2003
  • CJ-11668 is a new potent and selective COX-2 inhibitor (IC$\sub$50/ COX-2 65nM; COX-l/COX-2 ratio 770). The pharmacokinetic profile of CJ-11668 (20 mg/kg, p.o.) in the rat was characterized by high bioavailability (90%) and long plasma half-life (11.7 hr) with low clearance (0.4 L/hr/kg). In the dog, the PK profiles (2 mg/kg, p.o.) also showed long plasma half-life (l7.9hr) with low clearance (0.5 L/hr/kg), and the bioavalability of 60%. The inhibition of CJ-11668 infive different cytochrome P450 isozymes (1A2, 2C9, 2C19, 2D6 and 3A4) was determined in vitro and had observed no significant effect. (omitted)

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Association of gastric cancer with cytochrome P450 2C19 single-nucleotide polymorphisms in Koreans

  • Kim, Hyun-Ju;Park, Hye-Jung;Lee, Sang-Gyu;Lee, Hye-Suk;Park, Won-Cheol;Kim, Jeong-Joong;Oh, Gyung-Jae;Kim, Yun-Kyung
    • Advances in Traditional Medicine
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    • v.7 no.4
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    • pp.357-362
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    • 2007
  • Cytochrome P450 2C19 (CYP2C19) is a clinically important enzyme involved in the metabolism of therapeutic drugs, including (S)-mephenytoin, omeprazole, proguanil, and diazepam. Individuals are characterized as either extensive metabolizers (EM) or poor metabolizers (PM) on the basis of CYP2C19 enzyme activity. The PM phenotype occurs in 2-5% of Caucasians, but in 18-23% of Asians. To clarify the association between CYP2C19 polymorphisms and gastric cancer in Koreans, we investigated CYP2C19 genotypes ($CYP2C19^*1,\;{^*2},\;and\;^*3$) in 109 patients with gastric cancer and 211 controls. Normal ($CYP2C19^*1$) and defective alleles were detected with polymerase chain reaction/restriction enzyme analysis. CYP2C19 has three hereditary genotypes: homozygous EM, with high enzymatic activity; heterozygous EM, with moderate enzymatic activity; and PM, with no enzyme activity. We found that CYP2C19 heterozygous EM is more closely associated with gastric cancer than is homozygous EM. Because the CYP2C19 genotype varies in Koreans, a genotyping test is desirable to prevent gastropathy recurrence in patients before their doses of omeprazole are reduced during maintenance therapy.

Determination of Hydroxyapatite Precipitation Condition from the $Ca-PO_4-H_2O$ System ($Ca-PO_4-H_2O$계로부터 수산화아파타이트의 침전조건 결정)

  • Oh, Young-Jei
    • Analytical Science and Technology
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    • v.13 no.2
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    • pp.208-214
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    • 2000
  • The formation and dissolution of hydroxides, carbonates and hydroxyapatite (HAp), which depend on the pH of solution, are important factor for the preparation of homogeneous and fine HAp, $Ca_{10-x}(HPO_4)_x(PO_4)_{6-x}(OH)_{2-x}(x=0)$, ceramic powder from the $Ca-PO_4-H_2O$ system. Since the solubility of each complex ion is a linear function of pH, the solubility diagram can be obtained by plotting the logarithmic molar concentrations calculated from the values of the equilibrium constants and solubility products for hydroxides, carbonates, and hydroxyapatite. The optimum pH condition for the formation of single phase $Ca_{10-x}(HPO_4)_x(PO_4)_{6-x}(OH)_{2-x}(x=0)$ powder in $Ca-PO_4-H_2O$ system at $25^{\circ}C$ was estimated as $10.5{\pm}0.5$ through the theoretical consideration. The HAp powder dried at $80^{\circ}C$ showed a fine agglomerated particles with a size of 75 nm. The HAp powder calcined at $1,000^{\circ}C$ consisted of nearly homogeneous particles with a size of 450 nm. Even though the dried HAp particles consisted of agglomeration, mechanical properties were superior due to fine microstructure after sintering.

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Production of Mono-Hydroxylated Derivatives of Terpinen-4-ol by Bacterial CYP102A1 Enzymes

  • Jeong-Hoon Kim;Chan Mi Park;Hae Chan Jeong;Gyeong Han Jeong;Gun Su Cha;Sungbeom Lee;Chul-Ho Yun
    • Journal of Microbiology and Biotechnology
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    • v.34 no.3
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    • pp.725-734
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    • 2024
  • CYP102A1 from Bacillus megaterium is an important enzyme in biotechnology, because engineered CYP102A1 enzymes can react with diverse substrates and produce human cytochrome P450-like metabolites. Therefore, CYP102A1 can be applied to drug metabolite production. Terpinen-4-ol is a cyclic monoterpene and the primary component of essential tea tree oil. Terpinen-4-ol was known for therapeutic effects, including antibacterial, antifungal, antiviral, and anti-inflammatory. Because terpenes are natural compounds, examining novel terpenes and investigating the therapeutic effects of terpenes represent responses to social demands for eco-friendly compounds. In this study, we investigated the catalytic activity of engineered CYP102A1 on terpinen-4-ol. Among CYP102A1 mutants tested here, the R47L/F81I/F87V/E143G/L188Q/N213S/E267V mutant showed the highest activity to terpinen-4-ol. Two major metabolites of terpinen-4-ol were generated by engineered CYP102A1. Characterization of major metabolites was confirmed by liquid chromatography-mass spectrometry (LC-MS), gas chromatography-MS, and nuclear magnetic resonance spectroscopy (NMR). Based on the LC-MS results, the difference in mass-to-charge ratio of an ion (m/z) between terpinen-4-ol and its major metabolites was 16. One major metabolite was defined as 1,4-dihydroxyp-menth-2-ene by NMR. Given these results, we speculate that another major metabolite is also a mono-hydroxylated product. Taken together, we suggest that CYP102A1 can be applied to make novel terpene derivatives.

Explosion Characteristics Analysis of Low-Density Polyethylene Dust (저밀도 폴리에틸렌 분진의 폭발특성 분석)

  • Hyun-gil Kwon;Kyeong-seok Oh;Jong-bae Baek;Dong-hyun Seo
    • Korean Chemical Engineering Research
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    • v.61 no.1
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    • pp.80-88
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    • 2023
  • Ensuring safety in the designing of manufacturing and handling facilities for low-density polyethylene (LDPE) is difficult because there are no standards for the dust explosion characteristics of LDPE. In this study, a dust explosion test was performed on two dust samples collected from a bag filter (LDPE 1) during the LDPE manufacturing process and sedimentary dust (LDPE 2) leaked outside a facility such as a silo, and the LDPE 2 explosion test results were summarized. Particle size analysis showed that the volume-based particle diameter (median) was 95.04 ㎛ and the number density was 0-1 ㎛. The maximum explosion pressure (Pmax) was 6.6 bar, and the maximum rate of explosion pressure rise was 366 [bar/s] at 1500 g/m3. Accordingly, the dust explosion index (Kst) was 99.4 bar·m/s, which was confirmed as ST-1 grade. Moreover, the minimum ignition energy and minimum ignition temperature was 10 mJ and 450 ℃, respectively. Currently, manufacturing and handling design is based on the characteristic values of high-density polyethylene (HDPE). However, as the test results show that LDPE 2 dust has a higher risk than HDPE (particle diameter 61.6 ㎛), caution is required when using the HDPE design criteria in the LDPE manufacturing process.

Effects of the Co-treatment of Municipal Wastewater with Microwave-Irradiated Excess Sludge on the Performance of the Activated Sludge Process (초단파조사 처리된 잉여슬러지와 하수의 병합처리가 활성슬러지공법의 성능에 미치는 영향)

  • Kim, Nam-Chul;Jang, Myung-Bae;Cho, Yun-Kyung;Cho, Kwang-Myeung
    • Journal of Korean Society of Environmental Engineers
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    • v.29 no.3
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    • pp.304-310
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    • 2007
  • The purpose of this research was to investigate the effects of the co-treatment of municipal wastewater with microwave-irradiated excess sludge on the treatment efficiency and excess sludge production of the activated sludge process. When 250 mL of excess sludge with a MLSS concentration of approximately 2,000 mg/L was microwave-irradiated at $20^{\circ}C$ for $40\sim300$ sec by a microwave oven (2,450 MHz, 700 W), the temperature of the sludge increased at a rate of approximately $20^{\circ}C/min$ and the SCOD, TKN and T-P concentrations of the sludge showed the highest increase in the irradiation time of $40\sim130$ sec. And, the oxygen uptake rate measurement of the sludge microorganism suggested most of the microorganisms in the sludge were destroyed at an irradiation time above 130 sec(above $65^{\circ}C$). When the municipal wastewater and microwave-irradiated excess sludge was co-treated by the activated sludge process, almost no effect was observed in the pH and alkalinity of both the influent and effluent, but the influent concentrations of SS, COD, T-N and T-P increased. Even though the effluent SS, BOD and T-P concentrations showed almost no effect, the COD and TKN concentrations increased. The microbial yield coefficient decreased at a rate of 0.91 g SS/g COD removed as the irradiation ratio increased at a rate of 1 g SS/g SS-day.

Dna Methylation is Involved in the Regulation. of Mouse Cyp1A2 Expression

  • Bowhan Jin;Park, Dukwoong;Kim, Gyongsun;Ryu, Doug-Young
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2003.10b
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    • pp.152-152
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    • 2003
  • Cytochrome P450 1A2 (CYP1A2) is constitutively and inducibly expressed preferentially in liver of mice, but the molecular mechanisms underlying the expression of CYP1A2 have not yet been fully clarified. In this study, CpG sites of the Cyp1a2 promoter in liver were found to be hypomethylated in a site-specific pattern compared to those in lung and kidney.(omitted)

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The Effect of Temperature and Time on Physicochemical, Microbiological Properties and Sensory Analysis of Dongchimi during Fermentation and Storage (발효와 저장 중 온도와 시간 변화에 따른 동치미 품질 특성)

  • Cho, Mi Sook;Na, Yeseul
    • Journal of the Korean Society of Food Culture
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    • v.35 no.5
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    • pp.450-458
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    • 2020
  • This study examined the optimal temperature and time conditions to maintain high quality Dongchimi during the fermentation and storage period. Dongchimi was fermented at low (5℃), medium (10 and 15℃), and high (20℃) temperatures until the acidity reached 0.2, 0.3, and 0.4%. respectively. From the consumer's preference test enrolling five consumers, Dongchimi fermented at 15℃ until an acidity of 0.3% (for approximately six days) was evaluated to be the optimal status because of its high score of overall acceptance, taste, and odor of consumers. To determine the optimal storage temperature of fermentation, Dongchimi was stored at three different temperatures (-1, 2, 5℃) for four weeks after fermenting at 15℃ for six days. During the storage period, most of the physicochemical properties (pH, acidity, reducing sugar content, and organic acid) and microbiological properties changed significantly in the 2 and 5℃ groups, resulting in a significant change in descriptive sensory analysis of Dongchimi. These results indicate that fermentation at 15℃ and storage at -1℃ for Dongchimi enables it to maintain the best quality for a long time.

Adsorptive Stripping Voltammetry of the Indium-8-Hydroxyquinoline Complex (Indium-8-Hydroxyquinoline 착물에 관한 흡착벗김전압전류법적 연구)

  • Se Chul Sohn;Tae Yoon Eom;Moo Yul Suh;Ki-Suk Jung
    • Journal of the Korean Chemical Society
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    • v.35 no.2
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    • pp.151-157
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    • 1991
  • A sensitive stripping voltammetric study of the complex of indium with 8-hydroxyquinoline at a hanging mercury drop electrode was investigated in 0.1M acetate buffer solution. The effects of various analytical conditions on the reduction peak current of the adsorbed complex were discussed. Optimal analytical conditions were found to be the ligand concentration of $2 {\times}10^{-5}$M, solution pH 4.75, scan rate of 10 mV/s, deposition potential of -0.450V, a deposition time of 90 second. Interferences by other trace metals and Triton X-100 were also discussed. Detection limit was 0.2 ppb of indium after 90 sec. Deposition time, and the relative standard deviation(n = 10) at 4 ppb was 3.2%.

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