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101.
S Modi DE Gilham MJ Sutcliffe LY Lian WU Primrose CR Wolf GC Roberts 《Canadian Metallurgical Quarterly》1997,36(15):4461-4470
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a neurotoxin that produces Parkinsonism symptoms in man, has been examined as a substrate of recombinant human cytochrome P450 2D6. When cumene hydroperoxide is used as an oxygen and electron donor, a single product is formed, identified as 4-phenyl-1,2,3,6-tetrahydropyridine. The K(m) for formation of this product (130 microM) is in agreement with the dissociation constants for MPTP binding to the enzyme determined by optical and nuclear magnetic resonance (NMR) spectroscopy. When the reaction is carried out with nicotinamide adenine dinucleotide phosphate (reduced) (NADPH) and recombinant human NADPH-cytochrome P450 reductase, a second product, identified as 1-methyl-4-(4'-hydroxyphenyl)-1,2,3,6-tetrahydropyridine, is formed in addition to 4-phenyl-1,2,3,6-tetrahydropyridine. The K(m) values for formation of these two products are 19 microM and 120 microM, respectively. Paramagnetic relaxation experiments have been used to measure distances between the protons of bound MPTP and the heme iron, and these have been used to construct models for the position and orientation of MPTP in the active site. For the cytochrome alone, a single mode of binding was observed, with the N-methyl close to the heme iron in a position appropriate for the observed N-demethylation reaction. In the presence of the reductase, the data were not consistent with a single mode of binding but could be explained by the existence of two alternative orientations of MPTP in the active site. One of these, characterized by a dissociation constant of 150 microM, is essentially identical to that observed in the absence of the reductase. In the second, which has a K(d) of 25 microM, the MPTP is oriented so that the aromatic ring is close to the heme iron, in a position appropriate for p-hydroxylation leading to the formation of the product seen only in the presence of the reductase. In the case of codeine, another substrate for cytochrome P450 2D6, the addition of reductase had no effect on the nature of the product formed, the dissociation constant, or the orientation in the binding site. These observations show that NADPH-cytochrome P450 reductase has an allosteric effect on the active site of cytochrome P450 2D6 that affects the binding of some substrates but not others. 相似文献
102.
高速冷带轧机垂直自激振动稳定性分析的数值计算方法 总被引:5,自引:0,他引:5
本文在充分考虑轧机垂直振动过程中辊缝非线性的基础上,利用轧制理论方程和机械振动理论中的能量判据,给出了更精确的分析高速冷轧机垂直自激振动稳定性的数值计算方法。 相似文献
103.
104.
聚四氢呋喃及其下游产品的开发应用 总被引:2,自引:0,他引:2
本文论述了聚四氢呋喃技术进展、氨纶弹性纤维发展现状和国内外聚四氢呋喃产能和需求。 相似文献
105.
张峡 《核电子学与探测技术》2002,22(3):257-259
叙述了应用 Winsock技术与多线程技术实现高性能的 CAMAC通信服务器程序。介绍了整个程序的设计实现方法 ,重点介绍了网络通信服务的实现和多线程访问设备时的同步问题 相似文献
106.
107.
对几种增黑剂进行了筛选实验研究,选用了两种增黑剂组合使用,提高了遮盖力,使医用X光胶片涂布银量由原业的9g/m2降到了6.8g/m2,与美国医用X光胶片涂布银量(6.7g/m2)相当,照相性能不低于国产医用X光胶片。 相似文献
108.
109.
The effects of chronic injection of U50,488H (trans-3,4-dichloro-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeacetamidel++ +), a selective kappa opioid agonist, on the properties of the binding sites of tritiated U69593 [(5 alpha,7 alpha,8 beta)-(-)-N-methyl-N-(7-(1-pyrrolidinyl)-1-oxaspiro (4,5)dec-8-yl)benzeneacetamide], another selective kappa opioid agonist, and mechanical responses to U50,488H of the heart were studied. Rats received injection twice a day with U50,488H for 4 days. Binding studies on the crude membrane homogenates revealed that there was no change in maximum binding, but a significant increase in Kd after the treatment, indicating that the number of kappa binding sites remained unchanged whereas the affinity of the binding sites to kappa-agonist decreased. The study on the mechanical responses to U50,488H in the isolated perfused heart preparation showed that although the agonist at 10(-6) M caused MR2266 reversible reductions in heart rate and force of contraction as well as ventricular ectopic beat in the heart of rats in the control group, its effects were absent in the U50,488H-treated group, indicating the development of tolerance to the mechanical effects of U50,488H on the heart. The results indicate that the development of tolerance to the mechanical effects of a kappa-agonist after chronic treatment with the agonist was not accompanied by down-regulation, but only a slight and significant reduction in affinity of kappa binding sites in the rat heart. 相似文献
110.
This work reports the fabrication and the characterization of a new composite consisting of multiwalled carbon nanotubes (CNTs) and conducting titanium nitride (TiN) with a higher specific surface area ( S BET ), enhanced electrical conductivity (σ), and specific capacitance. With increasing CNT content, the electrical conductivity and electrochemical performance of the CNT–TiN composites gradually increase. In the presence of 5 wt% (12.0 vol%) CNTs, the electrical conductivity and the weight-specific capacitance of CNT–TiN composite are increased by 3.6 times and 54.8% compared with pure TiN, respectively. 相似文献