• Journal of Microbiology and Biotechnology
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• v.15 no.1
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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.

• Journal of Microbiology and Biotechnology
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• v.23 no.11
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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.

• Korean Chemical Engineering Research
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• v.44 no.1
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• pp.97-105
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• 2006

In order to investigate the effect of inhibitors on L-threonine biosynthesis in Escherichia coli, we have constructed a metabolic network model of amino acid biosynthesis from L-aspartate to L-threonine by using available informations from literatures and databases. In the model, the effects of inhibitors on the biosynthesis of L-threonine was included as an appropriate mathematical form. For simulation study, we used initial values as L-aspartate 5 mM, ATP 5 mM, NADPH 2 mM, and observed the concentration changes of intermediate metabolites over concentration changes of respective inhibitors. As a result, we found that concentrations of intermediate metabolites were not significantly changed over concentration changes of L-lysine, L-methionine, and L-glutamate. But, there were considerable changes of intermediates over concentration changes of L-serine, L-cysteine, and L-threonine, which can be considered as essential effectors on L-threonine synthesis. Contrary, the synthesis of L-threonine seems to be not related to the amounts of L-aspartate, and inversely proportional to the accumulated amount of D,L-aspartic ${\beta}$-semialdehyde.

• Bulletin of the Korean Chemical Society
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• v.33 no.11
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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.

• Korean Journal of Environmental Agriculture
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• v.16 no.2
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• pp.142-148
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• 1997

This study was performed to develop the biological treatment technology of wastewater polluted with heavy metals. Heavy metal-tolerant microorganisms, such as Pseudomonas putida, P. aeruginosa, P. chlororaphis and P. stutzeri possessing the ability to accumulate cadmium, lead, zinc and copper, respectively, were isolated from industrial wastewaters and mine wastewaters polluted with various heavy metals. The effect of competing ions and metabolic inhibitors on heavy metal accumulation in the cells was investigated. Heavy metal accumulation into cells was drastically decreased in the presence of competing cation, $Al^{3+}$, and also decreased, at a lesser extent, in the presence of competing anions, $CO_3\;^{2-}$ and $PO_4\;^{2-}$. But heavy metal accumulation was not influenced generally in the presence of the other rations and anions. The accumulation of Cd, Zn or Cu by Cd-, Zn- or Cu-tolerant microorganism was remarkably decreased in the presence of metabolic inhibitors, but the accumulation of Pb by Pb-tolerant microorganism was little affected in the presence of metabolic inhibitors. These results suggested that the accumulation of Cd, Zn or Cu by Cd-, Zn- or Cu-tolerant microorganism was concerned with the biological activity depending on energy, and the accumulation of Pb by Pb-tolerant microorganism depended on not the biological activity but the physical adsorption on the cell surface. Each heavy metal-tolerant microorganism also exhibited some ability to accumulate the other heavy metals in solution containing equal concentrations of cadmium, lead, zinc and copper, when measured at 48 hours after inoculation of the microorganisms, but the accumulation rates were somewhat low as compared to the accumulation rates of heavy metal fitting to each tolerance. These results suggested that the accumulation of each heavy metal by each heavy metal-tolerant microorganism was a selective accumulation process.

• Archives of Obesity and Metabolism
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• v.1 no.2
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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.

• KSBB Journal
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• v.10 no.2
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• pp.143-148
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• 1995

The effects of various elicitors, metabolic inhibitors and growth regulators on the production of diterpenoid anticancer agent taxol were investigated in cell suspension cultures of Taxus brevifolia. Cell cultures of T. brevifolia were treated by 5 kinds of biotic elicitors, 5 kinds of abiotic elicitors, 2 kinds of metabolic inhibitors and 8 kinds of growth regulators at the end of exponential growth phase. Among those treatments, chlorocholine chloride-an inhibitor of plant steroid metabolism-increased the taxol production most significantly. From a series of optimization studies, it was found that the addition of 1mM of chlorocholine chloride at the 9th day of culture was the best for taxol production. Taxol yield under this condition was 0.72mg/$\ell$.

• Microbiology and Biotechnology Letters
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• v.18 no.3
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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.

• Journal of Medicine and Life Science
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• v.20 no.3
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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.

• The Korean Journal of Zoology
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• v.11 no.3
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• pp.75-82
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• 1968

The effects of x-irradiation on the utilization of glucose, succinate, citrate and $\\alpha$-ketoglutarate, on the response of the cell metabolism to $NaN_3$ and DNP, and on the uptake of lysine in the presence or absence of the metabolitesor the inhibitors were studied using HeLa cells and the results are summarized as follows: 1. 200r of x-irradiation had no immediate effect on the oxygen consumption of cells. 2. The oxygen consumption was greatly stimulated by succinate, $\\alpha$-ketoglutarate and citraed and in decreasing order and x-irradiation caused no remarkable change in this order. 3. The respiratory response of the cell to the metabolic inhibitors seems to be altered by x-irradiation. 4. The initial rate of the uptake of lysine was markedly retarded and the accumulation of lysine in the cell was decreased by irradiation. 5. Glucose increased the lysine uptake whereas succinate had no effect and citrate and $\\alpha$-ketoglutarate reduced the absorption. X-irradiation did not alter this tendency. 6. The inhibitory effects of $NaN_3$ and DNP on the lysine uptake were quite different from those seen in the oxygen consumption.