Depiction of ¹³C labeling of cerebral metabolites from labeled glucose and acetate.

(A) Metabolism of [U-¹³C₆]glucose via glutamatergic and GABAergic TCA cycles labels Glu_4,5 which is de-carboxylated to GABA_1,2 in GABAergic neurons by GAD. Labeling of Gln_4,5 occurs from Glu_4,5 and GABA_1,2 via glutamate-glutamine and GABA-glutamine cycle. (B) As transporters of acetate are present on astroglia only, [2-¹³C]acetate is selectively transported and metabolized in these cells and labels Gln₄ by the combined action of astroglial TCA cycle and glutamine synthetase. Neurotransmitters Glu₄ and GABA₂ are labeled from Gln₄ via glutamate-glutamine and GABA-glutamine substrates cycling between astroglia and neurons. Isotopomers of Glu₄, GABA₂ and Gln₄ derived from [U-¹³C₆]glucose and [2-¹³C]acetate are different. Open and filled circles represent ¹²C and ¹³C atoms, respectively.