• Translational and Clinical Pharmacology
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• 제25권2호
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• pp.67-73
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• 2017

Glimepiride, a third generation sulfonylurea, is an antihyperglycemic agent widely used to treat type 2 diabetes mellitus. In this study, an untargeted urinary metabolomic analysis was performed to identify endogenous metabolites affected by glimepiride administration. Urine samples of twelve healthy male volunteers were collected before and after administration of 2 mg glimepiride. These samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and then subjected to multivariate data analysis including principal component analysis and orthogonal partial least squares discriminant analysis. Through this metabolomic profiling, we identified several endogenous metabolites such as adenosine 3', 5'-cyclic monophosphate (cAMP), quercetin, tyramine, and urocanic acid, which exhibit significant metabolomic changes between pre- and posturine samples. Among these, cAMP, which is known to be related to insulin secretion, was the most significantly altered metabolite following glimepiride administration. In addition, the pathway analysis showed that purine, tyrosine, and histidine metabolism was affected by pharmacological responses to glimepiride. Together, the results suggest that the pharmacometabolomic approach, based on LC-MS/MS, is useful in understanding the alterations in biochemical pathways associated with glimepiride action.

• Journal of Applied Biological Chemistry
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• 제66권
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• pp.467-476
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• 2023

오미자(Schisandra chinensis)는 오미자과에 속하는 낙엽활엽덩굴식물로 한국, 일본, 중국, 대만 등 동아시아에 널리 분포한다. 오미자에 함유된 주요 성분에는 리그난 화합물뿐만 아니라 트리테르페노이드 화합물도 포함되어 있는 것으로 보고되었다. 한국 산지별 오미자의 특성을 구별하기 위해 대사산물 프로파일링과 다변량 통계 분석 기법인 PCA을 수행하여 판별식을 설정하였고, 그 결과 triterpenoids 16종, lignan 9종, flavonoid, phenylpropanoid, fatty acid 각 1종을 동정하였다. 또한 다변량 통계분석을 통해 OPLS-DA의 s-plot 모델을 적용하여 단양, 문경, 거창, 평창의 4개 그룹을 구분하는 것을 확인하였고, lanostane, cycloartane, 그리고 schiartane triterpenoid, dibenzocyclooctadiene lignan 이 각각 화학적마커로 동정하였다.

• Journal of Nutrition and Health
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• 제24권3호
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• pp.199-205
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• 1991

비타민 A의 활성 대사물인 비타민 A arid(retinoir acid, Rh)를 사람의 간 조직내에서 처음으로 검출하고, 측정하는 방법을 고안하였다. Reverse phase HPLC에 gradient elution을 사용하는 이 방법은 Multiwavelength 검출법을 이용하여 RA, 비타민 A, 비타민 E 및 카로티노이드를 모두 약 30mg정도의 시료로부터 검출할 수 있었다. HPLC 분석에 소요되는 시간은 시료당 20분으로 상당히 신속하며 또 예민하다. 간 조직내의 총비타민 A량에 대한 Rh의 비율은 비타민 A의 축적량에 관계없이 일정한 편으로 약 $2.4\pm0.2%로$ 나타났다. RA의 간 조직내의 검출은 RA가 비타민 A의 체내 대사산물임을 다시 한번 확인시켰으며, 그 함량에 대한 정보는 총비타민 A량과 함께 비타민 A 영양 상태 판정에 보다 좋은 지표가 될 것이다. 특히 간 조직의 needle biopsy가 필요한 질병 상태의 경우, 비타민 A의 기능적 영양 상태판정을 가능하게 하여 질병의 진단 및 처치에 도움이 되리라 사료된다.

• Asian-Australasian Journal of Animal Sciences
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• 제30권9호
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• pp.1253-1260
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• 2017

Objective: Purpose was to determine the effects of grazing system and floor type on concentrations of blood metabolites, activity of creatine kinase, body weight and carcass characteristics of castrated Nguni goats. Methods: Forty eight, 7 month old goats were randomly allocated to herding and tethering treatments from 0800 to 1300 hours and accommodated on slatted and earth floors daily. Blood samples were collected by jugular venipuncture every fifteenth day for metabolite analysis. Slaughter was done at a commercial abattoir following 5 months of monitoring. Results: Tethered goats had significantly higher concentrations of urea (5.19 mmol/L) (p<0.001), creatinine ($55.87{\mu}mol/L$) (p<0.05), total protein (64.60 g/L) (p<0.01), and globulin (49.79 g/L) (p<0.001), whereas herded goats had higher glucose (3.38 mmol/L) (p<0.001), albumin (15.33 g/L) (p<0.05), albumin/globulin ratio (0.34) (p<0.01), and body weight (24.87 kg) (p<0.001). Slatted floors caused higher (p<0.01) albumin at 15.37 g/L. The interaction of grazing system and floor type affected creatinine, total protein, globulin at (p<0.01) and albumen/globulin ratio at (p<0.01). The least creatinine concentration and albumin/globulin ratio was in herded and tethered goats that were accommodated on earth floors, respectively. The highest total protein and globulin concentrations were in serum of tethered goats that were accommodated on earth floors. The highest (p<0.05) dressing percentage (45.26%) was in herded goats accommodated on slatted floors. Conclusion: Herding of goats lowered globulin concentration, improved estimated feed intake, blood glucose and albumin concentrations, albumin globulin ratio, increased body weights and weight related carcass characteristics. Floor type had very little effects on metabolites where earth floors only reduced albumin concentration. Tethering and housing goats on earth floors resulted in double stress that increased chronic infections.

• KSBB Journal
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• 제21권5호
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• pp.366-370
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• 2006

UDP-glucose는 ${\beta}$-1,3-glucan 합성의 중요한 전구체로 이를 측정함으로써 세포 내의 glucan synthesis 대사의 활성도를 추정할 수 있는 중요한 지표가 됨을 본 연구 결과를 통하여 알 수 있었다. UDP-glucose는 세포 성장기에 다량 생산되다가 ${\beta}$-1,3-glucan 합성하는 시기에 일정한 농도가 되며 ${\beta}$-1,3-Glucan 합성 메카니즘에서 glucose를 운반하는 중요한 역할을 하는 것으로 나타났다. 2단 연속 발효조를 이용하여 세포 성장 발효조와 ${\beta}$-1,3-glucan 생산 발효조에서 UDP-glucose 변화를 관찰하여 ${\beta}$-1,3-glucan 생산시 농도가 높음을 관찰할 수 있었다. ${\beta}$-1,3-Glucan 생산 발효조의 pH를 5.5로 조절함으로써 UDP-glucose의 농도를 증가시킬 수 있을 뿐만 아니라 ${\beta}$-1,3-glucan의 생산 속도를 최적화할 수 있었다.

• Mass Spectrometry Letters
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• 제3권1호
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• pp.21-24
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• 2012

$5{\alpha}$-Dihydrotestosterone (DHT) is the primary active metabolite of testosterone, catalyzed by $5{\alpha}$-reductase ($5{\alpha}R$) in the skin, prostate, and liver. In this study, the $5{\alpha}R$ activity in rat liver S9 fraction in the presence of a NADPH-generating system was evaluated and compared by gas chromatography-mass spectrometry (GC-MS)-based in vitro assays. Testosterone and a $5{\alpha}R$ inhibitor, finasteride, were added to the S9 fractions and incubated at $37^{\circ}C$ for 1 h. Both testosterone and DHT were quantitatively measured and compared with two different GC-MS-based steroid profiling techniques. DHT was not detected by conventional GC-MS analysis in the absence of finasteride when the concentration of testosterone in the S9 fraction was less than $0.2{\mu}M$, whereas the isotope-dilution GC-MS (GC-IDMS) system was able to evaluate the $5{\alpha}R$ activity. Because the S9 fraction contains more reactive enzymes and is easier to collect from tissues compared with a microsomal solution, the combination of the S9 fraction and GC-IDMS technique may be a promising assay for evaluating the $5{\alpha}R$ activity in large-scale clinical studies.

• 대한한의학방제학회지
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• 제22권1호
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• pp.105-112
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• 2014

Background and objective: Methamphetamine (Meth) is a widely abused psychostimulant that produces hyperlocomotion in rodents. Radix of Glycyrrhizae uralensis comprises a variety of bioactive components that have neuroprotective effects. In a previous study, we have demonstrated methanol extracts from radix of Glycyrrhizae uralensis (MEGR) suppress acute cocaine-induced extracellular dopamine release in the nucleus accumbens. In the present study, we investigated the effect of MEGR on acute Meth-induced hyperlocomotion. Methods: Male Sprague-Dawley rats were orally administered with MEGR (60 mg/kg and 180 mg/kg) 60 min prior to an intraperitoneal injection of Meth (1.0 mg/kg). Results: Behavioral analysis showed acute Meth greatly increased locomotor activities, while pretreatment with MEGR dose dependently inhibited the hyperlocomotion. In parallel, there were markedly increased levels of dopamine and its metabolite 3, 4-dihydroxyphenylacetic acid in the nucleus accumbens tissues in Meth-treated rats, which were also almost completely reversed by 180 mg/kg MEGR. Conclusions: These results showed that radix of Glycyrrhizae uralensis attenuates Meth-induced hyperlocomotion by inhibiting dopamine synthesis and utilization, suggesting that radix of Glycyrrhizae uralensis might be effective in blocking the rewarding effect of Meth.

• 한국생물정보학회:학술대회논문집
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• 한국생물정보시스템생물학회 2003년도 제2차 연례학술대회 발표논문집
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• pp.251-257
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• 2003

Metabolic engineering has become a new paradigm for the more efficient production of desired bioproducts. Metabolic engineering can be defined as directed modification of cellular metabolism and properties through the introduction, deletion, and modification of metabolic pathways by using recombinant DNA and other molecular biological tools. During the last decade, metabolic flux analysis(MFA) has become an essential tool fur metabolic engineering. By MFA, the intracellular metabolic fluxes can be quantified by the measurement of extracellular metabolite concentrations in combination with the stoichiometry of intracellular reactions and mass balances. The usefulness and functionality of MFA are demonstrated by applying to metabolic pathways in E. coli. First, a large-scale in silico E. coli model is constructed, and then the effects of carbon sources on intracellular flux distributions and succinic acid production were investigated on the basis of the uptake and secretion rates of the relevant metabolites. The results indicated that succinic acid yields increased in order of gluconate, glucose and sorbitol. Acetic acid and lactic acid were produced as major products rather than when gluconate and glucose were used carbon sources. The results indicated that among three carbon sources available, the most reduced substrate is sorbitol which yields efficient succinic acid production.

• 한국미생물·생명공학회지
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• 제46권1호
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• pp.40-44
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• 2018

Gram 양성세균의 생육을 억제하는 세균을 청주시 무심천 토양에서 분리하였으며, 16S rRNA 유전자 염기서열 분석 결과 Pseudomonas otitidis PS로 동정하였다. PS 균주는 0.5%의 glucose가 포함된 1% soybean meal 배지에서 2차 대사 산물로서 최대 약 0.1%의 수율로 항생물질을 생산하였다. 항생물질 성분은 ethyl acetate로 추출하였으며, Staphylococcus aureus KCTC 1261에 대한 minimum inhibitory concentration은 $2{\mu}g/ml$이었다. 이 성분은 siderophore 활성을 띠어서 chrome azurol S 평판배지에서 주황색 halo를 나타내었으며, 철이 제거되면 생육 억제 효과는 감소하였다. Ascorbic acid 같은 환원제를 첨가하거나 혐기적 환경에서는 항생물질 활성을 잃으므로 PS 항생물질은 활성산소를 방출하여 bactericidal activity를 갖는 것으로 보인다.

• Environmental Analysis Health and Toxicology
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• 제29권
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• pp.18.1-18.9
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• 2014

Objectives The purpose of this study was to determine a separation method for each arsenic metabolite in urine by using a high performance liquid chromatography (HPLC)-inductively coupled plasma-mass spectrometer (ICP-MS). Methods Separation of the arsenic metabolites was conducted in urine by using a polymeric anion-exchange (Hamilton PRP X-100, $4.6mm{\times}150mm$, $5{\mu}m$) column on Agilent Technologies 1260 Infinity LC system coupled to Agilent Technologies 7700 series ICP/MS equipment using argon as the plasma gas. Results All five important arsenic metabolites in urine were separated within 16 minutes in the order of arsenobetaine, arsenite, dimethylarsinate, monomethylarsonate and arsenate with detection limits ranging from 0.15 to $0.27{\mu}g/L$ ($40{\mu}L$ injection). We used G-EQUAS No. 52, the German external quality assessment scheme and standard reference material 2669, National Institute of Standard and Technology, to validate our analyses. Conclusions The method for separation of arsenic metabolites in urine was established by using HPLC-ICP-MS. This method contributes to the evaluation of arsenic exposure, health effect assessment and other bio-monitoring studies for arsenic exposure in South Korea.