Combined analysis of NMR and MS spectra (CANMS)

Cellular metabolism in mammalian cells represents an emerging challenge for analytical chemistry in the context of current biomedical research. Mass spectrometry (MS) and Nuclear Magnetic Resonance (NMR) spectroscopy in connection with computational tools have been used to study metabolism in cells. Compartmentalization of metabolism complicates the interpretation of stable isotope patterns in mammalian cells owing to the superimposition of different pathways contributing to the same pool of analytes in whole cell extracts. This indicates a need for a model-free approach to interpret such tracer-based data. MS and NMR provide complementary analytical information for metabolites with partial label incorporation in different positions. Here we present an approach that first simulates 13C-multiplets in NMR spectra and utilizes mass increments to obtain long-range information. In a second step the combined information is utilized to derive isotopomer distributions for key metabolites. This is a first rigorous analytical and computational approach for a model-free analysis of metabolic flux data applicable to mammalian cells.