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R J Morgan 《BMJ (Clinical research ed.)》1993,306(6893):1686-1687
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S de Vries S P Albracht J A Berden E C Slater 《The Journal of biological chemistry》1981,256(23):11996-11998
Using a combination of EPR and low temperature diffuse reflectance spectroscopy, a new species of semiquinone anion has been detected in QH2:cytochrome c oxidoreductase in submitochondrial particles under conditions of oxidant-induced extra reduction of cytochrome b. In contrast to the previously detected semiquinone anion, this new species is insensitive to antimycin but sensitive to treatment with 2,3-dimercaptopropanol and O2. The two species can easily be distinguished on the basis of their respective EPR properties since they differ in g-value, line width, and microwave power saturation behavior. It is concluded that the two species of semiquinone anion are bound to different domains on QH2:cytochrome c oxidoreductase. The existence of two different semiquinone anions in the enzyme strongly supports a mechanism of electron flow as proposed in the Q-cycle. 相似文献
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Noradrenaline caused a prompt but transient increase in the rate of45Ca2+ efflux from isolated rat islets of Langerhans perifused in Ca2+ depleted medium. The response was modest in size and was unaffected by isosmotic replacement of NaCl with choline chloride or by inclusion of 0.5 mM dibutyryl cAMP in the perifusion medium, suggesting that it was not mediated by Na+: Ca2+ exchange nor by lowered cAMP. Despite its effect on45Ca2+ efflux, noradrenaline treatment did not alter the kinetics of45Ca2+ efflux in response to the muscarinic agonist, carbamylcholine, nor did it change the magnitude of the response to this agent. Simultaneous introduction of 20 mM glucose with noradrenaline prevented a rise in45Ca2+ efflux and indeed resulted in inhibition of45Ca2+ efflux. The data suggest that noradrenaline does not directly activate the mechanisms which regulate Ca2+ extrusion from islets cells, and they do not support a primary role for the Ca2+ efflux response in mediating adrenergic inhibition of insulin secretion. 相似文献
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Susanne Berglund Bryan J. Egner Henrik Gradén Joakim Gradén David G.A. Morgan Tord Inghardt Fabrizio Giordanetto 《Bioorganic & medicinal chemistry letters》2009,19(15):4268-4273
Herein, we disclose the discovery and optimization of 2-piperidin-4-yl-acetamide derivatives as MCH-R1 antagonists. Structural investigation of piperidin-4-yl-amide and piperidin-4-yl-ureas identified 2-piperidin-4-yl-acetamide-based MCH-R1 antagonists with outstanding in vivo efficacy but flawed with high affinity towards the hERG potassium channel. While existing hERG SAR information was employed to discover highly potent MCH-R1 antagonists with minimized hERG inhibition, additional hurdles prevented their subsequent clinical exploration. 相似文献
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Pseudomonas aeruginosa and P. denitrificans accumulate more protoheme and considerably more protoporphyrin during anaerobic growth under denitrifying conditions than during aerobic growth. In Escherichia coli, the small accumulation of protoporphyrin and protoheme which occurs during anaerobic growth is slightly stimulated by nitrate and markedly stimulated by oxygen. 相似文献