The relationships between the metabolic fluxes and 13C-labeled isotopomer distribution for the flux analysis of the main metabolic pathways
The relationships between the metabolic fluxes and 13C-labeled isotopomer distribution for the flux analysis of the main metabolic pathways
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DOI：
10.1016/j.bej.2010.01.007
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发表时间：
2010-05-15
影响因子：
3.9
通讯作者：
Shimizu, Kazuyuki
中科院分区：
文献类型：
--
作者：
Matsuoka, Yu;Shimizu, Kazuyuki
已知c -13标记技术在估计代谢通量方面是非常有用的。尽管基于程序的流量分析功能强大，但在实践中，如果没有经验和基于置信区间统计分析的详尽试错，所得到的结果并不容易令人信服。因此，掌握碳同位素通量与碳-13标记同位素分布之间的关系，对深入了解代谢通量分析具有重要意义。在目前的研究中，它明确地显示了同位素分布是如何变化的通量与底物的标记模式有关，其中标记葡萄糖，醋酸盐或丙酮酸盐被用作碳源。基于矩阵表示导出了一些解析表达式，并将其用于分析。结果表明，同位素形态不一定随通量的变化而均匀变化，而是以一种复杂的方式变化，特别是在使用丙酮酸作为碳源的情况下，某些同位素形态不一定单调变化。结果表明，掌握同位素形态随通量的变化以及底物的标记形态对通量测定和实验设计是非常重要的。从信息指标的角度来看，[1-C-13]醋酸酯和[2-C-13]醋酸酯的混合物不宜使用。用本方法对部分实验数据进行了评价。结果还表明，在可逆途径中，同位素体分布对双向通量不太敏感。(C) 2010 Elsevier B.V.版权所有
It has been known that C-13-labeling technique is quite useful in estimating the metabolic fluxes. Although the program-based flux analysis is powerful, it is not easy to be confident with the result obtained without experiences and exhaustive trial and errors based on statistical analysis for the confidence intervals in practice. It is, therefore, quite important to grasp the relationship between the fluxes and the C-13-labeled isotopomer distribution to get deeper insight into the metabolic flux analysis. In the present research, it was shown explicitly how the isotopomer distribution changes with respect to the fluxes in relation to the labeling patterns of the substrate, where either labeled glucose, acetate, or pyruvate was used as a carbon source. Some of the analytical expressions were derived based on the matrix representation, and they were utilized for analysis. It was shown that the isotopomer pattern does not necessarily change uniformly with respect to fluxes, but changes in a complicated way in particular for the case of using pyruvate as a carbon source where some isotopomers do not necessarily change monotonically. It was shown to be quite important to grasp how the isotopomer pattern changes with respect to fluxes and the labeling pattern of the substrate for flux determination and the experimental design. It was also shown that the mixture of [1-C-13] acetate and [2-C-13] acetate should not be used from the information index point of view. Some of the experimental data were evaluated from the present approach. It was also shown that the isotopomer distribution is less sensitive to the bidirectional fluxes in the reversible pathway. (C) 2010 Elsevier B.V. All rights reserved.