Metabolic modeling of dynamic brain 13C NMR multiplet data: Concepts and simulations with a two-compartment neuronal-glial model

Alexander A. Shestov, Julien Valette, Dinesh K. Deelchand, Kǎmil Ugurbil, Pierre Gilles Henry

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Metabolic modeling of dynamic 13C labeling curves during infusion of 13C-labeled substrates allows quantitative measurements of metabolic rates in vivo. However metabolic modeling studies performed in the brain to date have only modeled time courses of total isotopic enrichment at individual carbon positions (positional enrichments), not taking advantage of the additional dynamic 13C isotopomer information available from finestructure multiplets in 13C spectra. Here we introduce a new 13C metabolic modeling approach using the concept of bonded cumulative isotopomers, or bonded cumomers. The direct relationship between bonded cumomers and 13C multiplets enables fitting of the dynamic multiplet data. The potential of this new approach is demonstrated using Monte- Carlo simulations with a brain two-compartment neuronalglial model. The precision of positional and cumomer approaches are compared for two different metabolic models (with and without glutamine dilution) and for different infusion protocols ([1,6-13C2]glucose, [1,2-13C2]acetate, and double infusion [1,6-13C2]glucose + [1,2-13C2]acetate) . In all cases, the bonded cumomer approach gives better precision than the positional approach. In addition, of the three different infusion protocols considered here, the double infusion protocol combined with dynamic bonded cumomer modeling appears the most robust for precise determination of all fluxes in the model. The concepts and simulations introduced in the present study set the foundation for taking full advantage of the available dynamic 13C multiplet data in metabolic modeling.

Original languageEnglish (US)
Pages (from-to)2388-2401
Number of pages14
JournalNeurochemical Research
Issue number11
StatePublished - Nov 2012

Bibliographical note

Funding Information:
Acknowledgments This work was supported by NIH grants P41R R008079, P41EB015894, P30NS057091 and R01NS038672 (P.G.H.).


  • Bonded cumomer
  • Brain
  • C Magnetic resonance spectroscopy
  • Isotopomer
  • Metabolic modeling
  • Monte-Carlo simulation
  • Neuronal-glial metabolism


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