Figure 3.

Sampling of brain extracellular metabolite levels versus assays of metabolism. Glucose is taken up and metabolized by neurons and astrocytes via the glycolytic pathway (glucose to pyruvate), pentose phosphate shunt pathway (PPP), and tricarboxylic acid (TCA) cycle. Glutamine is synthesized in astrocytes via the pyruvate carboxylase reaction to generate a “new” molecule of oxaloacetate that condenses with acetyl CoA from a second pyruvate molecule to sequentially form α-ketoglutarate, glutamate, and glutamine. The glutamine is shuttled to neurons where it serves as precursor for the glutamate and GABA neurotransmitter pools. Glutamate released to interstitial fluid during excitatotory neurotransmission is avidly taken up into astrocytes, and converted (in part) to glutamine for transfer back to neurons. This process is called the glutamate-glutamine (Glu-Gln) cycle and the cycle rate is directly proportional to the rate of oxidative metabolism over a wide range of brain activity levels (reviewed by Rothman et al.²²). Cerebral metabolic rates (CMR) can be determined by assay of arteriovenous differences (A-V) and cerebral blood flow (CBF) rates to obtain global rates, use of [¹⁸F]fluorodeoxyglucose-positron emission tomography (FDG-PET) to assay the hexokinase (HK) step and obtain total glucose utilization, or assays of oxidation of ¹³C-labeled substates using MRS and metabolic modeling. Glycogen is contained predominantly in astrocytes and it is a dynamic participant in brain metabolism. Microdialysis samples the ECs of compounds in ECF. After entry into cells (IC: intracellular concentration), compounds are metabolized via different pathways to generate ATP that provides energy for the cells. Note that ECs are the net balance of influxes and effluxes to and from blood and brain cells, whereas intracellular concentrations are the net balance between transport and metabolism. Glc: glucose; Lac: lactate; Pyr: pyruvate; Glu: glutamate; Gln: glutamine. Modified from Figure 1 of Dienel GA and Cruz NF. Contributions of glycogen to astrocytic energetics during brain activation. Metab Brain Dis 2015; 30: 281–298. Copyright © 2014, Springer Science+Business Media New York, with permission.