Flux determination by isotopomer balancing – a successful application of theory to experiment

Abstract

Metabolic flux analysis is an ever increasing theoretical framework that not only includes metabolite balancing but also linear programming approaches, network analyses and isotopomer balancing. The isotopomers of a given type of molecule are the various combinations of positions of labelled atoms. For example, when the 12C isotope can be replaced by 13C independently at each position in glucose, there are 64 (26 = 64) different isotopomers. Modern NMR techniques allow the measurement of some or all isotopomer fractions of many substances; this yields more information than measuring isotope fractions (positional enrichments). In a biotechnological context, it is of great interest to determine in vivo fluxes. These cannot, however, be measured directly using NMR but can only be calculated from the isotope and/or isotopomer fractions (provided that at least one flux is known for scaling). The relevant equations are, however, nonlinear.Recently, Wiechert et al 1xBidirectional reaction steps in metabolic networks: III. Explicit solution and analysis of isotopomer labeling systems. Wiechert, W et al. Biotechn. Bioeng. 1999; 66: 69–85Crossref | Scopus (190)See all