Bonded cumomer analysis of tumor metabolism based on 13C magnetic resonance spectroscopy. (17th March 2022) - Shestov, Alexander A.
Abstract : Bonded cumomers are sets of isotopomers of 13 C‐labeled metabolites containing a particular sequence of contiguously or singly labeled carbon atoms. Only these isotopomers contribute to multiplet structure in the 13 C 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 13 C 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 13 C glucose tracers on fine‐structure multiplets is analyzed. Abstract : Methodology and advantages of the bonded cumomer formulation of dynamic metabolic network analysis are described. Multiplets in the 13 C NMR spectrum originate from contiguously isotopically labeled carbon atoms called bonded cumomers. Bonded cumomers are natural isotopic variables in kinetic differential equations. Solution of these equations describes the dynamics profiles of the corresponding multiplets. Analysis of these multiplet profiles yields a description of the corresponding metabolic network of fluxes and metabolic parameters like the Warburg effect, mitochondrial or glycolytic energy production.