FIGURE 1.

Schematic of ¹³C labeling of amino acids from [1,6-¹³C₂]glucose. Metabolism of [1,6-¹³C₂]glucose via glutamatergic and GABAergic TCA cycles labels [4-¹³C]glutamate, which is decarboxylated to [2-¹³C]GABA by GAD enzyme present specifically in GABAergic neurons. Labeling of [4-¹³C]glutamine occurs from [4-¹³C]glutamate and [2-¹³C]GABA via glutamate–glutamine and GABA–glutamine cycle. Further metabolism of [4-¹³C]glutamate and [2-¹³C]GABA in the corresponding TCA cycle incorporates label into [2-¹³C]/[3-¹³C]glutamate and [3-¹³C]/[4-¹³C]GABA, respectively. [3-¹³C]Pyruvate, the glycolytic product of [1,6-¹³C₂]glucose is also metabolized by pyruvate carboxylase pathway (PC), and incorporates label into [2-¹³C]glutamine, [2-¹³C]glutamate, and [4-¹³C]GABA. For the simplicity, ¹³C labeling of amino acids from [1,6-¹³C₂]glucose via the first turn of TCA cycle is depicted. Abbreviations used are: αKG, α-ketoglutarate; OAA, oxaloacetate; Asp, aspartate; GABA, γ-aminobutyric acid; Glu, glutamate; Gln, glutamine; V_{cyc(GABA-Gln)}, GABA–glutamine cycling flux; V_cyc(Glu-Gln), glutamate–glutamine cycling flux; V_gad, glutamate decarboxylase flux; V_gln, glutamine synthesis rate; V_pc, pyruvate carboxylase flux; V_shunt, flux of GABA shunt; V_tca(A), Astroglial TCA cycle flux; V_tca(GABA), GABAergic TCA cycle flux; V_tca(Glu), glutamatergic TCA cycle flux; V_x, exchange rate between α-ketoglutarate and glutamate. ^∗Represents the position of ¹³C carbon.