Compartmentation of Glutamine, Glutamate, and GABA Metabolism in Neurons and Astrocytes: Functional Implications

The classical concept regarding compartmentation of brain metabolism pertinent to the two neurotrans-mitter amino acids, glutamate and GABA (γ-aminobutyrate), operates with different pools of glutamate and glutamine in different cell types, that is, pools that have different sizes and turnover rates. As a result of more sophisticated technology (e.g., nuclear magnetic resonance spectroscopy and mass spectrometry used in relation to cultured neurons and astrocytes), a more complex scenario is emerging. Hence, both neurons and astrocytes exhibit a compartmentalized metabolism that very likely relates to individual cells containing mitochondrial populations having different metabolic roles. Models for this in neurons and astro-cytes, respectively, are presented. The functional implications of this for the homeostatic mechanisms regulating the levels of neurotransmitter glutamate and GABA are discussed in relation to development of therapeutic strategies for neurological disorders in which these transmitters are believed to play important roles.