Numerical isotopomer analysis: estimation of metabolic activity

The use of stable isotopes to analyze intracellular metabolism is a powerful technique because of the wealth of information contained in the distribution of isotopes in key metabolites. We present a new numerical method of using measurements of isotope isomer (isotopomer) distributions to calculate the fluxes through a biochemical reaction network. Nuclear magnetic resonance (NMR) and/or mass spectroscopy can quantify the isotopomers which result from the metabolism of an isotopically enriched substrate. These data can be analyzed via a numerical model of the metabolic network which uses atom-mapping matrices to simplify model construction. The atom-mapping matrices describe the transfer of atoms from reactant to product and the resulting isoopomer balance equations are compact and intuitive. These equations are solved iteratively to determine the unknown intracellular fluxes. Results from the numerical method agreed with an analytical solution developed for the analysis of the tricarboxylic acid cycle in perfused hearts.