• 제목/요약/키워드: Acetyl coenzyme A

검색결과 39건 처리시간 0.025초

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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    • 제29권
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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.

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

  • 김태준;김진석;최정섭;장해성;조광연
    • 농약과학회지
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    • 제5권2호
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    • pp.58-61
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    • 2001
  • Fenoxaprop-ethyl R(+), S(-) 및 racemic mixture의 벼와 피에 대한 온실조건에서 제초활성 및 선택성과 aryloxyphenoxypropionate계열 제초제의 작용점으로 알려진 ACCase의 억제정도를 비교하였다. 온실에서의 벼와 피에 대한 식물체반응에서 R(+) 이성체가 가장 강한 생육저해를 보였고, S(-) 이성체에서 가장 약한 반응을 나타내어 fenoxaprop-ethyl R(+) 이성체가 활성형태임을 확인하였다. 온실에서 피에 대한 억제정도는 ACCase에 대한 in vitro 억제반응의 결과와 일치하여 fenoxaprop의 작용점은 효소 ACCase임을 알았다. 벼, 피간의 선택성 지수의 비교에서 온실실험의 결과 R(+)과 racemic mixture인 경우에는 각 각의 값이 0.6과 0.8로 비교적 낮았으나, S(-) 이성체의 경우에는 약 1.5로써 S(-) 이성체의 벼에 대한 안전성 폭이 R(+) 이성체보다 넓은 것으로 나타났다. 하지만, 이러한 경향이 in vitro수준에서는 이성체간 선택성지수의 차이는 인정되지 않았다. 따라서 작용점상에서 fenoxaprop-ethyl의 벼, 피간 근본적 선택성은 존재하지 않는 것으로 판단된다.

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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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    • 제7권5호
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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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Isonicotinic Acid Hydrazid (INH)의 불활성화(不活性化)에 관한 연구(硏究) (The Inactivation of Isonicotinic Acid Hydrazid (INH))

  • 김재백
    • Journal of Pharmaceutical Investigation
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    • 제9권3호
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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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산국의 잎과 줄기에서 ACAT 저해활성을 가지는 Guaianolides의 분리 (Isolation of Guaianolides with ACAT Inhibitory Activity from the Leaves and Stems of Chrysanthemum boreale Makino)

  • 이종록;박문기
    • 한국환경과학회지
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    • 제26권11호
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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 $100{\mu}g/mL$.

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

  • 장재현;김예지;노태용;박중곤
    • Korean Chemical Engineering Research
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    • 제54권5호
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    • pp.665-670
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    • 2016
  • 본 연구에서는 톨루엔 분해 균주인 Pseudomonas putida와 아세트산 분해 균주인 Cupriavidus necator에 무세포 효소 시스템(cell-free enzyme system)을 적용하여 톨루엔과 아세트산에 대한 분해 가능성을 확인하는 실험을 수행하였다. P. putida는 톨루엔 존재 하에서만 toluene dioxygenase를 생성하여 톨루엔을 cis-toluene dihydrodiol로 분해하며, C. necator는 acetyl coenzyme A synthetase-1을 생성하여 아세트산을 acetyl CoA로 전환시켜 생존에 필요한 ATP나 생분해성(biodegradable) 고분자인 Polyhydroxyalkanoate (PHA)를 합성한다. P. putida의 톨루엔 분해 효소인 toluene dioxygenase는 유도효소이기 때문에 toluene dioxygenase 생성 전과 후로 나누어 실험을 진행하였다. P. putida의 톨루엔 분해능력 확인을 위한 gas chromatography (GC) 분석 결과, 대조군과 toluene dioxygenase 생성 전인 실험군 1에서는 검출된 톨루엔의 양이 거의 유사하였으나, toluene dioxygenase 생성 후인 실험군 2에서는 검출된 톨루엔의 양이 대조군 및 실험군 1에 비해 감소하였다. 또한 C. necator의 아세트산 분해능력 확인을 위한 gas chromatography-mass spectrometer (GC-MS) 분석 결과, 무세포 효소 시스템을 적용한 실험군에서는 아세트산에 대한 피크가 검출되지 않았다. 따라서 P. putida와 C. necator는 무세포 효소 시스템 적용 후에도 톨루엔 및 아세트산 분해 능력이 유지되었으나, P. putida는 무세포 효소 시스템을 적용하기 전에 유도 효소를 생성하는 과정이 필요하다.

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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    • 제24권1호
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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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    • 제13권5호
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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
    • 한국응용약물학회:학술대회논문집
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    • 한국응용약물학회 2003년도 Annual Meeting of KSAP : International Symposium on Pharmaceutical and Biomedical Sciences on Obesity
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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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