• Title/Summary/Keyword: Acetyl coenzyme A

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New evidences of neurotoxicity of aroclor 1254 in mice brain: potential of coenzyme q10 in abating the detrimental outcomes

  • Majumdar, Anuradha;Nirwane, Abhijit;Kamble, Rahul
    • Environmental Analysis Health and Toxicology
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    • v.29
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    • pp.1.1-1.7
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    • 2014
  • Objectives The present subacute study was designed to evaluate the effect of coenzyme Q 10 (CoQ10) in the 28 days aroclor 1254 exposure induced oxidative stress in mice brain. Methods Biochemical estimations of brain lipid peroxidation (LPO), reduced glutathione (GSH), and activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and acetyl cholinesterase (AChE), and histopathological investigations of brain tissue were carried out. Results Oral exposure of aroclor 1254 (5 mg/kg) led to significant decrease in levels of GSH, and activities of SOD, CAT, GPx, and AChE, and increase in LPO. These aberrations were restored by CoQ10 (10 mg/kg, intraperitoneal injection [IP]). This protection offered was comparable to that of L-deprenyl (1 mg/kg, IP) which served as a reference standard. Conclusions Aroclor 1254 exposure hampers the activities of various antioxidant enzymes and induces oxidative stress in the brains of Swiss albino mice. Supplementation of CoQ10 abrogates these deleterious effects of aroclor 1254. CoQ10 also apparently enhanced acetyl cholinesterase activity which reflects its influence on the cholinergic system.

Chiral effect of fenoxaprop-ethyl on rice (Orysa sativa) and barnyardgrass (Echinochloa crus-galli) (벼와 피에 대한 Fenoxaprop-ethyl의 이성체효과)

  • Kim, Tae-Joon;Kim, Jin-Seog;Cho, Jeong-Sup;Chang, Hae-Sung;Cho, Kwang-Yun
    • The Korean Journal of Pesticide Science
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    • v.5 no.2
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    • pp.58-61
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    • 2001
  • A greenhouse study was conducted to evaluate the effect of R(+), S(-) and racemic mixture of fenoxaprop-ethyl on rice and barnyardgrass. In addition, in wire acetyl-coenzyme A carboxylase inhibition to those chiral compounds was determined. In the greenhouse trial, the R(+) and S(-) fenoxaprop showed respectively tile highest and the lowest biological activity on both plants. This dose-response in whole plant level was consistent with the result of in vitro dose-response of acetyl-coenzyme A carboxylase. These results corfirmed tllat the R(+) isomer is biologically more active than the S(-) isomer, and the target site of fenoxaprop is the enzyme acetyl-coenzyme A carboxylase. It was an interesting result that rice safety was improved in the S(-) isomer compared with the R(+), and the respective selectivity index was 1.5 and 0.57 in a greenhouse experiment; however, those values resulting from ACCase assay were not substantially different each other at in vitro level. Those results suggested that the fundamental selectivity of fenoxaprop-ethyl between rice and barnyardgrass would not exist at target site level.

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Enantioselective N-Acetylation of 3-Amino-3-phenylpropionic Acid by Cell-free Extracts of Streptomyces neyagawaensis

  • Chung, Myung-Chul;Lee, Ho-Jae;Lee, Choong-Hwan;Chun, Hyo-Kon;Kho, Yung-Hee
    • Journal of Microbiology and Biotechnology
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    • v.7 no.5
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    • pp.329-332
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    • 1997
  • Cell-free extracts of Streptomyces neyagawaensis SL-387 grown on a chemically defined medium supplemented with DL-3-amino-3-phenylpropionic acid (APP) produced N-acetyl-APP (Ac-APP) in the presence of APP and acetyl coenzyme A. The APP obtained by acid hydrolysis of the Ac-APP was D-configuration: $[\alpha]_D+6.5^{\circ}(H_2O)\;at\;20^{\circ}C$, optical purity 92% enantiomeric excesses (ee). These results suggest that an N-acetyltransferase exists in the cell-free extract as a novel enzyme with specificity for D-APP.

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The Inactivation of Isonicotinic Acid Hydrazid (INH) (Isonicotinic Acid Hydrazid (INH)의 불활성화(不活性化)에 관한 연구(硏究))

  • Kim, Jae-Baek
    • Journal of Pharmaceutical Investigation
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    • v.9 no.3
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    • pp.1-8
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    • 1979
  • The main route of metabolism of isonicotinic acid hydrazid (INH) in man is its conjugation with acetyl coenzyme A to form acetyl-INH. The reaction is catalyzed by an N-acetyl transferase in the liver. The acetylated drug can be excreted by the kidney more efficiently than INH, and the biological half-life of the drug in the body depends upon how rapidly the drug can be acetylated. This report measured the concentration of INH in the blood of 147 individuals 6 hours after they received a standard dose (9.8mg/kg) and plotted the data as a frequeney distribution hiotogram. There was bimodality, with a mean for one subpopulation at approximately $0.6{\sim}0.8\;mcg/ml.$, and a mean for the other subpopulation between 2.8 and 4.0mcg/ml. As might be expected slow acetylators of INH are more likely to develop a cumulative toxicity to the drug. The principle ,toxicity to INH is a peripheral neuritis but this adverse effect can be prevented by given extra pyridoxin to the patients, and the vitamin does not alter the antitubercular activity of INH. This report carried out that pyridoxine does not alter the ratio of free INH to the total INH in blood.

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Isolation of Guaianolides with ACAT Inhibitory Activity from the Leaves and Stems of Chrysanthemum boreale Makino (산국의 잎과 줄기에서 ACAT 저해활성을 가지는 Guaianolides의 분리)

  • Lee, Jong Rok;Park, Moon Ki
    • Journal of Environmental Science International
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    • v.26 no.11
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    • pp.1275-1284
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    • 2017
  • Acyltransferase (AT) catalyzes the transfer of an acyl moiety from acyl-coenzyme A (acyl-CoA) to an acceptor. ATs play important roles in the maintenance of homeostasis in the human body and have been linked to various diseases; therefore, several ATs have been proposed as potential targets for the treatment or prevention of such diseases. The AT family includes acyl-CoA:cholesterol AT (ACAT), diacylglycerol AT, and monoacylglycerol AT for the metabolism of lipids. Furthermore, recent molecular biological studies revealed the existence of their isozymes with distinct functions in the body. ACAT plays a critical role in the formation of cholesteryl esters from cholesterol and fatty acids, and is a potential target for treating hypercholesterolemia. During an experiment designed to discover biologically active compounds from herbal medicines, we isolated two known guaianolide sesquiterpene lactones from Chrysanthemum boreale Makino (Compositae). The lactones were characterized from their spectroscopic data (NMR, IR, MASS). These compounds were subjected to ACAT inhibition assay. Here, we report the isolation and structural elucidation of the compounds 8-o-acetyl-2-methoxy-10-hydroxy-3,11(13)-guaiadiene-12,6-olide and 8-acetyl-3,10-hydroxy-4(15),11(13)-guaiadiene-12,6-olide. In the ACAT inhibition assay, compound 1 showed strong inhibitory activity, with an $IC_{50}$ value $45{\mu}g/mL$, whereas compound 2 did not exhibit significant inhibitory activity with an over $100{\mu}g/mL$.

Degradation of Toluene and Acetic Acid Using Cell-Free Enzyme System from Single Cell-Strain (Single cell-strain부터 유래된 무세포 효소 시스템을 이용한 톨루엔 및 아세트산 분해)

  • Jang, Jae Hyun;Kim, Yeji;Roh, Tae Yong;Park, Joong Kon
    • Korean Chemical Engineering Research
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    • v.54 no.5
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    • pp.665-670
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    • 2016
  • This study deals with the possible degradation of toluene and acetic acid when subjected to cell-free enzyme system from the toluene degrading bacteria Pseudomonas putida and acetic acid degrading bacteria Cupriavidus necator. P. putida produces toluene dioxygenase only under the existence of toluene in culture medium and toluene is degraded to cis-toluene dihydrodiol by this enzyme. C. necator produces acetyl coenzyme A synthetase-1 and converts acetic acid to acetyl CoA in order to synthesize ATP to need for growth or PHA which is biodegradable polymer. In case of toluene degradation, the experiment was conducted before and after production of toluene dioxygenase as this enzyme, produced by P. putida, is an inducible enzyme. Toluene was detected using gas chromatography (GC). Similar amount of toluene was found in control group and before production of toluene dioxygenase (experimental group 1). However, reduction in toluene was detected after the production of toluene dioxygenase (experimental group 2). Acetic acid was detected through application of gas chromatography-mass spectrometer (GC-MS). The results showed the acetic acid peak was not detected in the experimental group to apply cell-free enzyme system. These results show that the cell-free enzyme system obtained from P. putida and C. necator retained the ability to degrade toluene and acetic acid. However, P. putida needs to produce the inducible enzyme before preparation of the cell-free enzyme system.

Medium- and long-chain triglyceride propofol reduces the activity of acetyl-coenzyme A carboxylase in hepatic lipid metabolism in HepG2 and Huh7 cells

  • Wang, Li-yuan;Wu, Jing;Gao, Ya-fen;Lin, Duo-mao;Ma, Jun
    • The Korean Journal of Physiology and Pharmacology
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    • v.24 no.1
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    • pp.19-26
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    • 2020
  • Medium- and long-chain triglyceride (MCT/LCT) propofol is widely used as an intravenous anesthetic, especially in the intensive care unit. The present study aimed to assess whether MCT/LCT propofol is safe in the hyperlipidemic population for long-term use. Free fatty acids (FFAs) were used to establish high-fat stimulation of HepG2 and Huh7 cells. Subsequently, these cells were treated with propofol at the concentration of 0, 4, or 8 ㎍/ml for 24 and 48 h. The results indicated that the cell viability was notably decreased when the cells were stimulated with 2 mmol/L FFAs and treated with 12 ㎍/ml MCT/LCT propofol. Accordingly, we chose 2 mmol/L FFAs along with 4 and 8 ㎍/ml MCT/LCT propofol for the subsequent experiments. Four and 8 ㎍/ml MCT/LCT propofol inhibited FFA-induced lipid accumulation in the cells and significantly reversed acetyl coenzyme A carboxylase (ACC) activity. In addition, MCT/LCT propofol not only significantly promoted the phosphorylation of AMPK and ACC, but also reversed the FFA-induced decreased phosphorylation of AMPK and ACC. In conclusion, MCT/LCT propofol reverses the negative effects caused by FFAs in HepG2 and Huh7 cells, indicating that MCT/LCT propofol might positively regulate lipid metabolism.

Heterologous Expression of Hybrid Type II Polyketide Synthase System in Streptomyces Species

  • Kim, Chang-Young;Park, Hyun-Joo;Kim, Eung-Soo
    • Journal of Microbiology and Biotechnology
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    • v.13 no.5
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    • pp.819-822
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    • 2003
  • Polyketides are an extensive class of secondary metabolites with diverse molecular structures and biological activities. A plasmid-based minimal polyketide synthase (PKS) expression cassette was constructed using a subset of actinorhodin (act) biosynthetic genes (actI-orfl, actI-orf2, actI-orf3, actIII, actⅦ, and actIV) from Streptomyces coelicolor, which specify the construction of an orange-fluorescent anthraquinone product aloesaponarin II, a type II polyketide compound derived from one acetyl coenzyme A and 7 malonyl coenzyme A extender units. This system was designed as an indicator pathway in S. parvulus to generate a hybrid type II polyketide compound via gene-specific replacement. The act ${\beta}-ketoacyl$ synthase unit (actI-orfl and actI-orf2) in the expression cassette was specifically replaced with oxytetracycline ${\beta}-ketoacyl$ synthase otcY-orfl and otcY-orf2). This plasmid-based hybrid PKS cassette generated a novel orange-fluorescent compound structurally different from aloesaponarin II in both S. lividans and S. parvulus. In addition, several additional distinctive blue-fluorescent compounds were detected, when this hybrid PKS cassette was expressed in S. coelicolor B78 (actI-orf2 mutant), implying that the expression of plasmid-based hybrid PKS cassette in Streptomyces species should be an efficient way of generating hybrid type II polyketide compounds.

Soluble isocitrate dehydrogenase plays a key role in obesity and hyperlipidemia

  • Koh, Ho-Jin;Lee, Su-Min;Huh, Tae-Lin
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2003.11a
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    • pp.5-7
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    • 2003
  • NADPH is an essential co-factor for fat and cholesterol biosynthesis. However, the role of cytosolic NADP$\^$+/-dependent isocitrate dehydrogenase (IDPc), a putative NADPH producer, in the control of the fat and cholesterol metabolism has not been assessed. Here we report that increased or decreased IDPc expression in 3T3-Ll fat cells promoted or retarded adipogenesis, respectively. Furthermore, overexpression of IDPc in transgenic mice exhibited fatty liver, hypertriglyceridemia, hypercholesterolemia and obesity by increasing NADPH production leading to subsequent stimulation of acetyl-coenzyme A and malonyl-coenzyme A consumption. In contrast, administrations of a synthetic IDPc inhibitor, DAl1004, to ob/ob mice effectively reduced body weight with lowering cholesterol and triglyceride levels. In addition, a positive relationship (${\gamma}$ = 0.69, $\rho$<0.0l) between plasma IDPc activity and body mass indexes was observed in 98 randomly-selected human volunteers. Our findings strongly indicate that NADPH produced by IDPc plays an important role in controlling body fat and lipid biosynthesis.

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