Modeling isotopomer distributions in biochemical networks using isotopomer mapping matrices

作者：Schmidt Karsten, Morten Carlsen, JENS KVIST NIELSEN, John Villadsen · 发表于：Biotechnology and Bioengineering · 年份：1997 · DOI：10.1002/(sici)1097-0290(19970920)55:6<831::aid-bit2>3.0.co;2-h · 被引用次数：304 · 研究领域：Microbial Metabolic Engineering and Bioproduction、Metabolomics and Mass Spectrometry Studies、Bioinformatics and Genomic Networks

Within the last decades NMR spectroscopy has undergone tremendous development and has become a powerful analytical tool for the investigation of intracellular flux distributions in biochemical networks using (13)C-labeled substrates. Not only are the experiments much easier to conduct than experiments employing radioactive tracer elements, but NMR spectroscopy also provides additional information on the labeling pattern of the metabolites. Whereas the maximum amount of information obtainable with (14)C-labeled substrates is the fractional enrichment in the individual carbon atom positions, NMR spectroscopy can also provide information on the degree of labeling at neighboring carbon atom positions by analyzing multiplet patterns in NMR spectra or using 2-dimensional NMR spectra. It is possible to quantify the mole fractions of molecules that show a specific labeling pattern, i.e., information of the isotopomer distribution in metabolite pools can be obtained. The isotopomer distribution is the maximum amount of information that in theory can be obtained from (13)C-tracer studies. The wealth of information contained in NMR spectra frequently leads to overdetermined algebraic systems. Consequently, fluxes must be estimated by nonlinear least squares analysis, in which experimental labeling data is compared with simulated steady state isotopomer distributions. Hence, mathematical models are required to compute the steady state isotopomer distribution as a function of a given set ...