a systems biology approach to investigating apoptotic stimuli as effectors of cell metabolism practical application of top-down control analysis to attached neurons系统生物学的方法研究凋亡刺激的感受器细胞代谢自上而下控制的实际应用分析神经元连接.pdfVIP

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a systems biology approach to investigating apoptotic stimuli as effectors of cell metabolism practical application of top-down control analysis to attached neurons系统生物学的方法研究凋亡刺激的感受器细胞代谢自上而下控制的实际应用分析神经元连接.pdf

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a systems biology approach to investigating apoptotic stimuli as effectors of cell metabolism practical application of top-down control analysis to attached neurons系统生物学的方法研究凋亡刺激的感受器细胞代谢自上而下控制的实际应用分析神经元连接

Int. J. Mol. Sci. 2009, 10, 702-722; doi:10.3390/ijm OPEN ACCESS International Journal of Molecular Sciences ISSN 1422-0067 /journal/ijms Review A Systems Biology Approach to Investigating Apoptotic Stimuli as Effectors of Cell Metabolism: Practical Application of Top-Down Control Analysis to Attached Neurons Mika B. Jekabsons Department of Biology, University of Mississippi / 110 Shoemaker Hall, University, MS 38677 USA; E-Mail: jekabson@; Tel. +1-662-915-3998; Fax: +1-662-915-5144 Received: 20 January 2009; in revised form: 19 February 2009 / Accepted: 19 February 2009 / Published: 23 February 2009 Abstract: Reduced glycolytic and mitochondrial respiration rates are common features of apoptosis that may reflect key events contributing to cell death. However, it is unclear to what extent the rate changes can be explained by direct alterations in the kinetics of the participating reactions, as changes in the concentrations of intermediates also affect reaction rates. Direct kinetic changes can be identified, ranked, and compared to the indirect effects mediated by the intermediates using top-down control analysis. Flux changes that are explained primarily by direct effects are likely to be prime targets of the pathways that signal death, and thus important contributors to apoptosis. Control analysis concepts relevant to identifying such effects are reviewed. Metabolic