Bonded cumomer analysis of tumor metabolism based on 13C magnetic resonance spectroscopy

Bonded cumomers are sets of isotopomers of C-13-labeled metabolites containing a particular sequence of contiguously or singly labeled carbon atoms. Only these isotopomers contribute to multiplet structure in the C-13 NMR spectrum. We discuss the application of this technique to the study of quantitative tumor metabolism, bioenergetics, and the Warburg effect. The advantages and sensitivity of bonded cumomer analysis over positional enrichment analysis are discussed. When sensitivity requirements are met, bonded cumomer analysis enables the extraction of fluxes through specific metabolic pathways with higher precision. In conjunction with isotopomer control analysis, we evaluate the sensitivity of experimentally measurable metabolite multiplets to determine the robustness of flux analysis in C-13 spectra of tumors. This review examines the role of glycolytic and tricarboxylic acid cycle metabolism with special emphasis on flux through the pentose phosphate pathway (PPP). The impact of reversibility of the nonoxidative branch of the PPP with various C-13 glucose tracers on fine-structure multiplets is analyzed.