Diagram of glial–neuronal metabolism of [1-13C]glucose and [1,2-13C]acetate

Diagram of glial–neuronal metabolism of [1-13C]glucose and [1,2-13C]acetate. The [1-13C]glucose is converted through glycolysis into one molecule of [3-13C]pyruvate, as well as one molecule of unlabeled pyruvate (not shown), in astrocytes and neurons. The [3-13C]pyruvate is then converted to either [3-13C]lactate in the cytosol, [3-13C]alanine in cytosol and mitochondria, oxaloacetate by pyruvate carboxylase in astrocyte mitochondria (for simplicity this pathway is not included), or [2-13C]acetyl CoA in neuronal and astrocytic mitochondria. The [2-13C]acetyl CoA condenses with oxaloacetate and enters the tricarboxylic acid cycle (TCA) cycle. The 13C label is then incorporated into TCA cycle intermediates, and can exit the cycle at the [4-13C]α-ketoglutarate step to form [4-13C]glutamate. In GABAergic neurons, [4-13C]glutamate is transformed into [2-13C]γ-aminobutyric acid (GABA) by glutamate decarboxylase (GAD). On release into the synaptic cleft, [4-13C]glutamate is taken up into astrocytes at which it can be converted to [4-13C]glutamine directly by the enzyme glutamine synthetase (GS), or enter the TCA cycle before conversion to [3 or 2-13C]glutamine. Ratios for the direct and indirect conversion can be calculated (see Materials and methods) and is shown in the figure as [glu–gln]direct and [glu–gln]indirect, respectively. Glutamine is transported back to the neurons where it is converted to glutamate by phosphate-activated glutaminase (PAG). The [1,2-13C]acetate is taken up into astrocytes and converted to [1,2-13C]acetyl CoA, which can enter the TCA cycle and result in the formation of [4,5-13C]glutamate that is rapidly converted to [4,5-13C]glutamine by the astrocytic GS. The ratio calculated for direct conversion of acetate-derived glutamine to glutamate is illustrated by [gln–glu]direct. Glutamine can be transported to neurons and regenerate [4,5-13C]glutamate via PAG, and subsequently give rise to [1,2-13C]GABA via GAD in GABAergic neurons. The ratio for this conversion is illustrated by [gln–GABA]direct in the figure. *Metabolism of [1-13C]glucose in astrocytes leads to the same labeling pattern as shown in neurons in the figure.

Publication

Reduced astrocytic contribution to the turnover of glutamate, glutamine, and GABA characterizes the latent phase in the kainate model of temporal lobe epilepsy. (2011) Silje Alvestad, et al. J Cereb Blood Flow Metab. 2011 Aug;31(8):1675-1686. Figure: F1.

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