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The complex isotopologue space of glucose as a framework for the study of human intermediary metabolism

The positional distributions of stable isotopes in metabolites provide specific fingerprints of the pathways and fluxes that have occurred in the organisms under study. In particular, modern nuclear magnetic resonance (NMR) spectroscopy enables the detailed assignment of isotope patterns in natural products, for example, in metabolites obtained from labelling experiments using 13C-enriched precursors, such as glucose, acetate or CO2. In this study, the transient 13C-isotopologue composition of blood glucose from an adult human volunteer after intravenous supply of [U-13C6]glucose was determined by high-resolution 13C NMR spectroscopy. The non-linear progression curves displaying the relative amounts of eight 13C-glucose isotopologues reflected the contributions of glucose metabolism by glycolytic cycling, the pentose phosphate pathway and anaplerotic reactions involving the citric acid cycle. The pilot study suggests that the experimental setting can be useful in analysing under non-invasive conditions the impact of physiological and pharmacological constraints on glucose turnover in humans.