New metabolic 13C isotopomer modeling approach for elucidating brain neuron‐glia metabolism

Abstract

Current brain two‐compartment neuronal‐glial metabolic models [1] use total 13C turnover curves at each carbon position (“positional models”) but do not take advantage of the additional information from 13C isotopomers, which appear as multiplets in 13C spectra and can now be measured and quantified in vivo [2], to determine metabolic fluxes, such as the glutamine‐glutamate neurotransmission flux VNT. We developed a new neuronal‐glial metabolic model (“isotopomer model”) capable of taking into account the additional information from 13C‐13C multiplets. The new metabolic model allows fitting of each dynamic NMR multiplet curve e.g. for glutamate obtained during i.v. C1,6‐glucose infusion (for example GluC4S, Glu‐C4D43, etc, Fig. 1). Monte‐Carlo simulations show that the new model leads to a significant improvement in the precision of metabolic fluxes (Fig. 2). For example, the standard deviation on VNT was 670% with the positional model and just 19% with the isotopomer model.Conclusion: we developed a new metabolic model to take into account the additional information from 13C isotopomers, which appear as multiplets in 13C spectra. The additional information provides significantly increased precision in fitted metabolic fluxes.This work was supported by NIH R01NS38672 and P41RR08079.