Tandem mass spectrometry: A novel approach for metabolic flux analysis

Tandem mass spectrometry: A novel approach for metabolic flux analysis
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DOI:
10.1016/j.ymben.2010.11.006
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发表时间:
2011-03-01
影响因子:
8.4
通讯作者:
Antoniewicz, Maciek R.
Antoniewicz, Maciek R.
中科院分区:
工程技术1区
文献类型:
--
作者:
Choi, Jungik;Antoniewicz, Maciek R.

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代谢流分析(MFA)的目标是准确估计代谢网络中的细胞内通量。在这里,我们介绍了一种新的方法MFA串联质谱(MS)和稳定同位素示踪实验的基础上。我们表明,串联MS提供更多的标记信息比可以从传统的全扫描MS分析,并允许估计通量具有更好的精度。我们提出了一个建模框架,充分利用额外的标签信息从串联MS MFA。我们表明,串联MS数据可以计算任何网络模型,任何化合物和任何串联MS碎片使用线性映射的同位素。利用模拟数据和文献数据,在两个网络模型中说明了串联MS的固有优势。串联MS的应用增加了模型的可观测性,并提高了2至5倍,传统的MS分析相比,估计通量的精度。(C)2010年爱思唯尔公司All rights reserved.
The goal of metabolic flux analysis (MFA) is the accurate estimation of intracellular fluxes in metabolic networks. Here, we introduce a new method for MFA based on tandem mass spectrometry (MS) and stable-isotope tracer experiments. We demonstrate that tandem MS provides more labeling information than can be obtained from traditional full scan MS analysis and allows estimation of fluxes with better precision. We present a modeling framework that takes full advantage of the additional labeling information obtained from tandem MS for MFA. We show that tandem MS data can be computed for any network model, any compound and any tandem MS fragmentation using linear mapping of isotopomers. The inherent advantages of tandem MS were illustrated in two network models using simulated and literature data. Application of tandem MS increased the observability of the models and improved the precision of estimated fluxes by 2- to 5-fold compared to traditional MS analysis. (C) 2010 Elsevier Inc. All rights reserved.