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21.
Comparative study of acetaldehyde, furfural and 5-hydroxymethyl furfural from celluloses which differed in crystallinity was made by pyrolytic gas chromatography.Pyrolysis of tobacco cellulose at 200~300°C resulted in rapid increase in the yields of furfurals from the amorphous regions in comparison with that from the crystalline regions. At 500°C, however, acetaldehyde was obtained in higher yields from microcrystalline cellulose than that from tobacco cellulose under the same condition.In thermogravimetric analysis, the threshold temperature for the pyrolysis of tobacco cellulose was lower than that of microcrystylline cellulose. These results showed that the yields of the volatile compounds from pyrolysis of cellulose depended on temperature and crystallinity. 相似文献
22.
《Process Biochemistry》2014,49(2):295-300
The perturbation in the growth and fatty acid profile of the microscopic fungus Cochliobolus lunatus IM 4417 in the presence of octyltin compounds (trioctyltin – TOT, dioctyltin – DOT and monooctyltin – MOT) was studied. Fungal resistance to the tested organotins decreased with a reduction in the number of octyl groups bonded with a tin atom. Also, the fatty acid unsaturation index decreased according to the mentioned scheme. Among all tested octyltin compounds, TOT was removed with the highest efficiency. The efficiency of MOT removal was correlated with the initial concentration of the compounds and for concentrations 20 and 100 mg l−1 reached the value of 75% and 40%, respectively. Elimination of octyltins depended on the metabolic activity of the fungus and was not the result of passive sorption. During bioconversion of TOT the hydroxylated derivative of substrate was detected. Moreover, the addition of cytochrome P-450 inhibitors significantly reduced the metabolism of octyltin compounds. Thus, it is postulated that the process of degradation of octyltin compounds is similar to that described for tributyltin (TBT) and it is mediated by cytochrome P-450. 相似文献
23.
We describe initial results on a Western blotting method, using a ployclonal antibody and chemiluminescence detection, for the measurement of cytochrome P450 2E1 in human lymphocytes. The method has been used to study the levels of 2E1 in lymphocytes isolated from 5 ml blood samples collected from a small group of well-controlled type 1 diabetics and healthy individuals. The described method offers increased sensitivity compared with a previously published method and does not need in vitro culturing of the lymphocytes prior to 2E1 measurement. The apparent molecular weight of the lymphocyte P450 2E1 was 55 kDa. There was approximately a six-fold difference in expression levels of 2E1 detected by this immunochemical technique across the study population. 相似文献
24.
The effects of pretreatment with toluene, o-, m-, p-xylene and mesitylene were investigated on the microsomal enzymes of liver, kidney and lung in rats. The activities of aminopyrine N-demethylase, aryl hydrocarbon hydroxylase, aniline hydroxylase, NADPH-cytochrome c reductase, as well as the concentrations of cytochrome P-450 and cytochrome b5 were determined. The effects were most marked in the liver, where toluene caused increase in aniline hydroxylase and cytochrome P-450; o-xylene in aminopyrine N-demethylase and cytochrome b5; m-xylene and mesitylene in all the enzymes investigated. In kidneys, all the compounds increased the activity of aniline hydroxylase; m-xylene induced cytochrome P-450 and b5 as well as NADPH-cytochrome c reductase; p-xylene induced cytochrome P-450, and mesitylene cytochrome P-450 and b5. Aminopyrine N-demethylase activity was decreased by toluene. In lungs, only mesitylene caused any significant differences from the controls: increase in aminopyrine N-demethylase and aryl hydrocarbon hydroxylase, decrease in aniline hydroxylase. The methylbenzenes tested induced the microsomal enzymes in a rough correlation to the number of their methyl groups and their hydrophobic properties. 相似文献
25.
Kristin E Williams Douglas L Anderton Maxwell P Lee Brian T Pentecost Kathleen F Arcaro 《Epigenetics》2014,9(2):297-307
Roughly two-thirds of all breast cancers are ERα-positive and can be treated with the antiestrogen, Tamoxifen, however resistance occurs in 33% of women who take the drug for more than 5 y. Aberrant DNA methylation, an epigenetic mechanism that alters gene expression in cancer, is thought to play a role in this resistance. To develop an understanding of Tamoxifen-resistance and identify novel pathways and targets of aberrant methylation, DNA from MCF-7 breast cancer cells and Tamoxifen-resistant derivatives, TMX2–11 and TMX2–28, were analyzed using the Illumina HumanMethylation450 BeadChip. Normalizing against MCF-7 values, ERα-positive TMX2–11 had 4000 hypermethylated sites and ERα-negative TMX2–28 had over 33 000. Analysis of CpG sites altered in both TMX2–11 and TMX2–28 revealed that the Tamoxifen-resistant cell lines share 3000 hypermethylated and 200 hypomethylated CpGs. ZNF350 and MAGED1, two genes hypermethylated in both cell lines, were examined in greater detail. Treatment with 5-aza-2′deoxycitidine caused a significant reduction in promoter methylation of both ZNF350 and MAGED1 and a corresponding increase in expression in TMX2–28. A similar relationship between methylation and expression was not detected in TMX2–11. Our findings are indicative of the variable responses to methylation-targeted breast cancer therapy and highlight the need for biomarkers that accurately predict treatment outcome. 相似文献
26.
Z. Gross Shay Nimri Claudia M. Barzilay Liliya Simkhovich 《Journal of biological inorganic chemistry》1997,2(4):492-506
A series of oxoiron(IV) porphyrin cation radical complexes was investigated as compound I analogs of cytochrome P-450. Both
the spectroscopic features and the reactivities of the complexes in oxygen atom transfer to olefins were examined as a function
of only one variable, the axial ligand trans to the oxoiron(IV) bond. The results disclosed two important kinetic steps – electron transfer from olefin to oxoiron(IV)
and intramolecular electron transfer from metal to porphyrin radical – which are affected differently by the axial ligands.
The large kinetic barrier of the latter step in the reaction of olefins with the perchlorato-bound oxoiron(IV) porphyrin cation
radical complex enabled the trapping of a reaction intermediate in which the metal, but not the porphyrin radical, is reduced.
The first electron transfer step is probably followed by σ-bond formation, which readily accounts for formation of isomerized
organic products at low temperatures. It is finally postulated that part of the enhanced oxygenation activities of cytochrome
P-450 monooxygenases and chloroperoxidases is due to a lowering of the energy barrier for the second electron transfer step
via participation of their redox-active cysteinate ligand.
Received: 16 January 1997 / Accepted: 24 May 1997 相似文献
27.
Manabu Nukaya Bernice C. Lin Edward Glover Susan M. Moran Gregory D. Kennedy Christopher A. Bradfield 《The Journal of biological chemistry》2010,285(46):35599-35605
The aryl hydrocarbon receptor (AHR) plays an essential role in the toxic response to environmental pollutants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin), in the adaptive up-regulation of xenobiotic metabolizing enzymes, and in hepatic vascular development. In our model of AHR signaling, the receptor is found in a cytosolic complex with a number of molecular chaperones, including Hsp90, p23, and the aryl hydrocarbon receptor-interacting protein (AIP), also known as ARA9 and XAP2. To understand the role of AIP in adaptive and toxic aspects of AHR signaling, we generated a conditional mouse model where the Aip locus can be deleted in hepatocytes. Using this model, we demonstrate two important roles for the AIP protein in AHR biology. (i) The expression of AIP in hepatocytes is essential to maintain high levels of functional cytosolic AHR protein in the mammalian liver. (ii) Expression of the AIP protein is essential for dioxin-induced hepatotoxicity. Interestingly, classical AHR-driven genes show differential dependence on AIP expression. The Cyp1b1 and Ahrr genes require AIP expression for normal up-regulation by dioxin, whereas Cyp1a1 and Cyp1a2 do not. This differential dependence on AIP provides evidence that the mammalian genome contains more than one class of AHR-responsive genes and suggests that a search for AIP-dependent, AHR-responsive genes may guide us to the targets of the dioxin-induced hepatotoxicity. 相似文献
28.
29.
Haijun Qu Xiaoxiao Hu Xiaoli Shi Chuan Wang Guoping Wang 《Animal cells and systems.》2019,23(3):155-163
N-(2-pyridylmethyl)-2-hydroxiymethyl-1-pyrrolidinyl-4-(3-chloro-4-methoxy-benzylamino)-5-pyrimidine-carboxamide (NHPPC) is a new potential of type 5 phosphodiesterase (PDE5) inhibitors, synthesized from the avanafil analogue for the treatment of erectile dysfunction. The targets of this article were to assess plasma protein binding, liver microsomal metabolic stability, inhibition and induction on cytochrome P450 isozymes and the pharmacokinetics of NHPPC. Equilibrium dialysis technique was applied to determine Plasma protein binding (PPB) and NHPPC was evaluated in male Sprague–Dawley rats and Beagle dogs in vivo pharmacokinetic. The NHPPC was highly bound to plasma proteins in rats, dogs and human tested and the mean values for PPB rate were 96.2%, 99.6% and 99.4%, respectively. After in vitro liver microsomes incubated for 60?min, the percent remaining of NHPPC was 42.8%, 0.8% and 42.0% in rats, dogs and human, respectively. In vitro intrinsic clearance was found to be 0.0233, 0.1204 and 0.0214 mL/min/mg protein in rat, dog and human liver microsomes of NHPPC, respectively. NHPPC showed no significant inhibitory effects on major CYP450 enzymes, and had no significant induction potential on CYP1A2 and CYP3A4. Following oral administration in rats and dogs, tmax was 6 and 0.5?h, respectively. The clearance for NHPPC was 1.19 and 1.46?L/h/kg in rats and dogs, respectively. And absolute bioavailability in rat and dog were approximately 34.5% and 53.1%, respectively. These results showed that NHPPC has a good development prospect. 相似文献
30.
《Bioorganic & medicinal chemistry letters》2019,29(16):2016-2024
Cytochromes P450 (CYPs) play an important role in the metabolism of endogenic and xenobiotic substances, especially drugs. In addition, many CYPs may serve as targets for disease treatment. However, due to the presence of a common heme, the hydrophobicity of the CYP binding cavity, and the high homology within the binding pocket, most CYP inhibitors lack selectivity, which often leads to drug-drug interactions. Therefore, it is meaningful to develop highly selective CYP inhibitors. In this review, we summarize some of the strategies that have been used to develop highly selective CYP inhibitors, such as the weakening of the heme-binding group interaction, reduction of molecular lipophilicity and introduction of small structural changes within compounds. 相似文献