• 제목/요약/키워드: metabolic inhibitors

검색결과 90건 처리시간 0.027초

Construction of Comprehensive Metabolic Network for Glycolysis with Regulation Mechanisms and Effectors

  • JIN, JONG-HWA;JUNG, UI-SUB;JAE, WOOK-NAM;IN, YONG-HO;LEE, SANG-YUP;LEE, DOHE-ON;LEE, JIN-WON
    • Journal of Microbiology and Biotechnology
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    • 제15권1호
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    • pp.161-174
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    • 2005
  • Abstract Glycolysis has a main function to provide ATP and precursor metabolites for biomass production. Although glycolysis is one of the most important pathways in cellular metabolism, the details of its regulation mechanism and regulating chemicals are not well known yet. The regulation of the glycolytic pathway is very robust to allow for large fluxes at almost constant metabolite levels in spite of changing environmental conditions and many reaction effectors like inhibitors, activating compounds, cofactors, and related metal ions. These changing environmental conditions and metabolic reaction effectors were focused on to understand their roles in the metabolic networks. In this study, we have investigated for construction of the regulatory map of the glycolytic metabolic network and tried to collect all the effectors as much as possible which might affect the glycolysis metabolic pathway. Using the results of this study, it is expected that a complex metabolic situation can be more precisely analyzed and simulated by using available programs and appropriate kinetic data.

Targeting Acetate Kinase: Inhibitors as Potential Bacteriostatics

  • Asgari, Saeme;Shariati, Parvin;Ebrahim-Habibi, Azadeh
    • Journal of Microbiology and Biotechnology
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    • 제23권11호
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    • pp.1544-1553
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    • 2013
  • Despite the importance of acetate kinase in the metabolism of bacteria, limited structural studies have been carried out on this enzyme. In this study, a three-dimensional structure of the Escherichia coli acetate kinase was constructed by use of molecular modeling methods. In the next stage, by considering the structure of the catalytic intermediate, trifluoroethanol (TFE) and trifluoroethyl butyrate were proposed as potential inhibitors of the enzyme. The putative binding mode of these compounds was studied with the use of a docking program, which revealed that they can fit well into the enzyme. To study the role of these potential enzyme inhibitors in the metabolic pathway of E. coli, their effects on the growth of this bacterium were studied. The results showed that growth was considerably reduced in the presence of these inhibitors. Changes in the profile of the metabolic products were studied by proton nuclear magnetic resonance spectroscopy. Remarkable changes were observed in the quantity of acetate, but other products were less altered. In this study, inhibition of growth by the two inhibitors as reflected by a change in the metabolism of E. coli suggests the potential use of these compounds (particularly TFE) as bacteriostatic agents.

대장균의 동역학 네트워크 모델을 이용한 L-threonine 생합성에 관한 모사 연구 (Simulation Study of Dynamic Network Model for L-Threonine Biosynthesis in Escherichia coli)

  • 정의섭;이진원
    • Korean Chemical Engineering Research
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    • 제44권1호
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    • pp.97-105
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    • 2006
  • 본 연구에서는 대장균 내에서 L-threonine의 생합성에 영향을 미치는 저해제들에 대한 모사 연구를 위하여 L-aspartate에서 L-threonine까지의 아미노산 생합성 대사 네트워크를 문헌 및 데이터베이스를 통해 구축하였다. 또한 L-threonine 생합성에 영향을 미치는 저해제들을 수학적으로 모델링하여 효소 반응식에 적용시켰다. 모사 연구를 위해 초기 농도값을 L-aspartate 5 mM, ATP 5 mM, NADPH 2 mM으로 설정하고 저해제의 농도 변화에 따른 세포내 대사 물질들의 농도변화를 확인하였다. 그 결과 저해제 L-lysine, L-methionine, L-glutamate는 저해제 농도 변화에 따라 대사 물질들의 농도 변화가 없었다. 그러나 저해제 L-serine, L-cysteine 그리고 L-threonine의 경우 저해제의 농도 변화에 따라 세포내 대사물질들의 농도 곡선이 서로 다른 결과를 얻었다. 대장균 내에서 소비되어진 L-aspartate의 농도는 세포 내 생성되는 L-threonine과는 관련이 없었고, 생성되는 L-threonine의 농도는 세포 내에 축적된 D,L-aspartic ${\beta}$-semialdehyde에 반비례하였다.

Virtual Screening and Biochemical Evaluation of Mitogen-activated Protein Kinase Phosphatase 4 Inhibitors

  • Park, Hwangseo;Jeon, Jeong-Yi;Ryu, Seong Eon
    • Bulletin of the Korean Chemical Society
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    • 제33권11호
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    • pp.3772-3776
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    • 2012
  • Mitogen-activated protein kinase phosphatase 4 (MKP4) has proved to be a promising target for the development of therapeutics for the treatment of diabetes and the other metabolic diseases. Here, we report an example for a successful application of the structure-based virtual screening to identify three novel inhibitors of MKP4. These inhibitors have desirable physicochemical properties as a drug candidate and reveal a moderate potency with $IC_{50}$ values ranging from 4.9 to $32.3{\mu}M$. Therefore, they deserve consideration for further development by structure-activity relationship studies to optimize the inhibitory and antidiabetic activities. Structural features relevant to the stabilization of the newly identified inhibitors in the active site of MKP4 are discussed in detail.

중금속내성균의 중금속 축적에 미치는 경쟁이온 및 대사저해제의 영향 (Influence of Competing Ions and Metabolic Inhibitors on Heavy Metal Accumulation in the Cell of Heavy Metal-Tolerant Microorganisms)

  • 조주식;이홍재;허종수
    • 한국환경농학회지
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    • 제16권2호
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    • pp.142-148
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    • 1997
  • 중금속오염폐수처리에의 미생물 이용 가능성을 검토하기 위하여 중금속에 강한 내성을 지님과 동시에 균체내 중금속 축적능력이 우수한 중금속 내성균을 분리하여 competing ion, 대사저해제 등과 같은 외부 요인에 따른 균체내 중금속 축적변화를 조사한 결과는 다음과 같다. 중금속을 처리한 용액중 양이온인 $Al^{3+}$이온과 음이온인 $CO_3\;^{2-}$$PO_4\;^{2-}$이온이 competing ion으로 존재할 경우 중금속 내성균의 균체내 중금속 축적은 크게 감소되었으나, 그외 다른 양이온들과 음이온들에 대해서는 거의 영향을 받지 않았다. Cd, Zn 및 Cu 내성균주의 Cd, Zn 및 Cu 축적은 대사저해제에 의하여 크게 감소되었으나, Pb 내성균주에 의한 Pb 축적은 거의 영향을 받지 않는 것으로 나타나 Cd, Zn 및 Cu 내성균주의 Cd, Zn 및 Cu 축적은 에너지 의존적인 과정으로서 물질대사와 관련되어 있는 것으로 생각되었으며, Pb 내성균주의 Pb 축적은 에너지 비의존적인 과정으로서 물질대사와 관련이 별로 없는 물리적인 과정에 의하여 축적되는 것으로 생각되었다. 각 중금속 내성균주들은 해당 중금속 축적능력에 비하여 낮았으나 타 중금속들의 축적능력도 있었으며, 여러가지 중금속들을 동일 농도로 복합처리 하였을 경우 해당 중금속들의 축적능력이 타 중금속들에 비하여 매우 높게 나타나 각 중금속 내성균주들의 해당 중금속 축적은 선택적인 과정에 의하여 축적되는 것으로 생각되었다.

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날트렉손/부프로피온 복합제 및 여러 기전의 약물을 이용하여 비만과 동반 대사질환을 치료한 고도비만환자 (Morbidly Obese Patients Treated Obesity and Metabolic Diseases Using Naltrexone/Bupropion Extended Release and Other Drugs of Various Mechanisms)

  • 조수현
    • 비만대사연구학술지
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    • 제1권2호
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    • pp.83-88
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    • 2022
  • Obesity increases the risk of developing metabolic diseases such as hypertension, type 2 diabetes, hyperlipidemia, and cardiovascular diseases, as well as some cancers. To prevent the occurrence of these diseases and death, it is essential to manage obesity. Though there are several treatments for obesity, lifestyle interventions, such as diet and exercise, and drug therapy are most widely used in clinical practice. Among the anti-obesity drugs available, the weight loss effect of naltrexone/bupropion has been well-proven. We present a case study in which naltrexone/bupropion, a glucagon-like peptide-1 agonist, and a sodium-glucose transporter 2 inhibitor showed significant weight loss and improved metabolic parameters. Additionally, the management of type 2 diabetes and hypertension, which are common diseases in patients with obesity, was also included.

주목세포배양에 의한 Taxol 생산: 여러 가지 Elicitor가 미치는 영향 (Taxol Production in Taxus Cell Cultures: Effects of Various Elicitors)

  • 윤정환;김진훈
    • KSBB Journal
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    • 제10권2호
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    • pp.143-148
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    • 1995
  • Taxus brevifolia 현탁세포배양에 서 항암제 taxol의 생산을 향상시키기 위해 5종류의 biotic elicitor 와 5종류의 abiotic elicitor, 2종류의 대사억제 및 8종류의 생장조절제를 세포배양 중에 첨가하여 효과 가 았는 물질을 선별하였다. T. brevifo/ia 현탁세포 배양의 대수증식기 말기인 10일째에 각각의 물질을 첨가하여 배양액 내의 taxol의 함량을 측정한 결과 steroid계 억제제 인 chlorocholine chloride를 처리 하였을 때 taxol의 생성이 현저히 증가되었다. Chloro choline chloride의 처리시기 및 처리농도를 다르게 하여 최적조건을 찾은 결과 9일째에 1mM을 첨가했 을 경우 taxol 생성이 가장 좋았다.

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카드뮴 내성 효모의 세포내 카드뮴 축적 기작 (Mechanism of Cadmium Accumulation into the Cell of Cadmium-Ion Tolerant Yeast)

  • 유대식;송형익;정기택
    • 한국미생물·생명공학회지
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    • 제18권3호
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    • pp.233-238
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    • 1990
  • The mechanism of intracellular accumulation of cadmium in a cadmium-ion tolerant yeast, Hansenula ammala B-7, which is an extreme cadmium tolerant strain and has the ability to take up a large amount of cadmium was investigated. The amounts of cadmium taken up by the scalded yeast cells were 2 to 3 times more than the value of the living cells. The living Hansenula anomala B-7 cells adsorbed 74% of cadmium taken up onto the other layer of the cells and 26% of it accumulated inside the cells. But the scalded cells adsorbed 98.3% of cadmium taken up and accumulated 1.7% of it inside the cells. A cadmium uptake and its accumulation were accelerated up to 162.3% and 275.4% by Triton X-100 in the living cells, respectively. Whereas in the scalded cell cadmium uptake was not affected by Triton X-100. Furthermore the cadmium uptake and its accumulation were strongly inhibited by metabolic inhibitors like 2,4-dinitrophenol, sodium azide and potassium cyanide in the living cells, but in the scalded cells cadmium uptake was not affected by metabolic inhibitors. These results suggested that the intracellular accumulation of cadmium by the cadmium-tolerant Hansenula anomala B-7 cells was apparently dependent of biological activity, and also gave evidence of the existance of energy-dependent system.

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Euglycemic diabetic ketoacidosis development in a patient with type 2 diabetes receiving a sodium-glucose cotransporter-2 inhibitor and a carbohydrate-restricted diet

  • Gwanpyo Koh;Jisun Bang;Soyeon Yoo;Sang Ah Lee
    • Journal of Medicine and Life Science
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    • 제20권3호
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    • pp.126-130
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    • 2023
  • Sodium-glucose cotransporter-2 (SGLT2) inhibitors have become increasingly prescribed because of their proven protective effects on the heart and kidneys, and carbohydrate-restricted diets are popular therapeutic approaches for patients with obesity and diabetes. A 28-year-old obese woman with recently diagnosed diabetes developed euglycemic diabetic ketoacidosis (DKA) while on dapagliflozin, an SGLT2 inhibitor, and following a carbohydrate-restricted diet. She presented with nausea, vomiting, and epigastric pain. Hospital tests showed a blood glucose of 172 mg/dL, metabolic acidosis, and increased ketone levels, confirming euglycemic DKA. Treatment involved discontinuing dapagliflozin and administering fluids, glucose, and insulin. She recovered and was discharged on the fourth day. This is considered a case of euglycemic DKA induced by SGLT2 inhibitors and triggered by a carbohydrate-restricted diet. This case highlights the importance of physicians in confirming the symptoms and laboratory results of DKA, even in patients with normal blood glucose levels taking SGLT2 inhibitors and following carbohydrate-restricted diets. It is also crucial to advise patients to maintain an adequate carbohydrate intake.

培養 HeLa 細胞의 酸素消費量과 Lysine 吸收에 미치는 X-線 照射의 影響 (Effects of X-irradiation on the Oxygen Consumption and Lysine Uptake of HeLa Cells in the Presence of Metabolic Substrates and Inhibitors)

  • Kang, Yung-Sun;Ha, Doo-Bong;Ahn, Kyung-Ja
    • 한국동물학회지
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    • 제11권3호
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    • pp.75-82
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    • 1968
  • 培養 HeLa 細胞의 酸素消費量과 Lysine 吸收에 미치는 X-線 照射의 영향을 측정하였다. 1. 200r의 X-線 照射는 酸素消費量에 아무러한 영향이 없다. 酸素消費量은 succinate, citrate, 및 $\\alpha$-ketoglutarate에 의하여 增大되며 X-線 照射群에서도 이 傾向은 同一하다. 2. 酸素消費量에 미치는 sodium azide 와 2,4-dinitrophenol 의 영향은 X-線 照射에 의하여 상당히 변화된다. 3. Lysine의 初期吸收率은 X-線 照射에 의하여 甚히 低下되며, 또한 飽和吸收量도 減少된다. 4. Glucose는 lysine의 吸收를 促進시키고, succinate는 아무러한 영향이 없으며 citrate와 $\\alpha$-ketoglutarate는 억제한다. X-線 照射는 이러한 傾向에 아무런 변화를 초래하지 않는다. 5. Lysine의 吸收에 미치는 sodium azide와 2,4-dinitrophenol의 영향은 酸素消費量에 미치는 이들의 영향과 判異하다. 이러한 傾向은 X-線 照射群에서도 대체로 동일하다.

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