Metabolite and isotopomer balancing in the analysis of metabolic cycles: I. Theory

Proper analysis of label distribution in metabolic pathway intermediates is critical for correct interpretation of experimental data and strategic exp erimental design. While, for example, C-13 nuclear magnetic resonance (NMR) spectroscopy is usually limited to the measurement of degrees of C-13 enri chment, more information about metabolic fluxes can be extracted from the f ine structure of NMR spectra, or molecular weight distributions of isotopom ers of metabolic intermediates (measured by gas chromatography-mass spectro metry). For this purpose, rigorous accounting for the contribution of all p athways to label distribution is required, especially contributions resulti ng from multiple turns of metabolic cycles, in this paper we present a math ematical model developed to analyze isotopomer distributions of tricarboxyl ic acid cycle (TCA) intermediates following the administration of C-13 (Or C-14) labeled substrates. The theory presented provides the basis to analyz e C-13 NMR spectra and molecular weight distributions of metabolites, in a companion paper (Park et al., 1999), the theory is applied to the analysis of several cases of biological significance. (C) 1999 John Wiley & Sons, In c.