The relationships between the metabolic fluxes and 13C-labeled isotopomer distribution for the flux analysis of the main metabolic pathways |
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| Institution: | 1. Department of Bioscience and Bioinformatics, Kyushu Institute of Technology, Iizuka, Fukuoka 820-8502, Japan;2. Institute of Advanced Bioscience, Keio University, Tsuruoka, Yamagata 997-0017, Japan;1. Department of Clinical Pharmacology, Xiangya Hospital, Central South University, 410078, Changsha, PR China;2. Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, Hunan, 410078, PR China;3. Hunan Provincial Tumor Hospital, The Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha, Hunan, 410013, PR China;1. Hainan Provincial Key Laboratory of Quality and Safety for Tropical Fruits and Vegetables, Analysis and Testing Center, Chinese Academy of Tropical Agriculture Sciences, Haikou 571101, PR China;2. Guangdong Institute of Eco-Environmental and Soil Sciences, Guangzhou 510650, PR China;1. Department of Food Engineering, Woosuk University, Jeonbuk, 55338, Republic of Korea;2. College of Pharmacy, Dankook University, Cheonan, 31116, Republic of Korea;3. College of Pharmacy, Woosuk University, Jeonbuk, 55338, Republic of Korea;1. School of Geographical Sciences, Guangzhou University, Guangzhou, 510006, China;2. Guangdong Province Engineering Technology Research Center for Geographical Conditions Monitoring and Comprehensive Analysis, Guangzhou University, Guangzhou, 510006, China |
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| Abstract: | It has been known that 13C-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 13C-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 1-13C] acetate and 2-13C] 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. |
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