(485o) Dynamic 13C Metabolic Modeling of Acetate Metabolism in Human Brain

Carbon-13 MRS combined with metabolic modeling allows measurement of metabolic rates in vivo. Most 13C metabolic modeling studies have been performed using 13C-glucose as the infused substrate. Acetate, glial-specific substrate, is an attractive alternative to glucose to study neuronal-glial interactions [1,2]. The goals of the present study were to determine kinetic parameters for acetate transport and utilization and to perform dynamic metabolic modeling of glutamate and glutamine 13C turnover curves obtained during [2-13C]acetate infusion in the human brain with a two-compartment neuronal-glial model.

Results

Fitted values for acetate transport and uptake kinetics were: Vtrmax=0.3±0.07 μmol/g/min and Vutmax=0.17±0.03 μmol/g/min assuming KtrM=4.2±1.8 mM and KutilM=0.01±0.14 mM for acetate transport and utilization respectively [3]. The steady-state cerebral metabolic rate of acetate (CMRace) was 0.061±0.02 μmol/g/min (mean ± SD; n = 4). Metabolic fluxes determined from metabolic modeling of the glutamate and glutamine 13C time courses were (in μmol/g/min): VTCA(n)=0.68±0.2, VTCA(g)=0.088±0.02, VPC=0.0±0.01, VX=0.83±0.2 and VNT=0.14±0.03. These values are in agreement with rates reported in previous studies [2,4].

Conclusion

Dynamic metabolic modeling of glutamate and glutamine 13C turnover curves measured during [2-13C]acetate infusion with a two-compartment neuronal-glial model is feasible and allows determination of compartmentalized metabolic rates.

References

[1] Bluml et al. NMR Biomed 2002 ; [2] Lebon et al. JNeurosci 2002 [3] Deelchand et al. JNeurochem 2009; [4] Gruetter et al . AJP 2001.

This work was supported by NIH P41RR008079, P30NS057091, R01NS038672 and the Keck Foundation.