The Glutamate/GABA-Glutamine Cycle

Mary C. McKenna, Gustavo C. Ferreira, McKenna, Mary C., Ferreira, Gustavo C.

Transient multienzyme and/or multiprotein complexes (metabolons) direct substrates toward specific pathways and can significantly influence the metabolism of glutamate and glutamine in the brain. Glutamate is the primary excitatory neurotransmitter in brain. This neurotransmitter has essential roles in normal brain function including learning and memory. Metabolism of glutamate involves the coordinated activity of astrocytes and neurons and high affinity transporter proteins that are selectively distributed on these cells. This chapter describes known and possible metabolons that affect the metabolism of glutamate and related compounds in the brain, as well as some factors that can modulate the association and dissociation of such complexes, including protein modifications by acylation reactions (e.g., acetylation, palmitoylation, succinylation, SUMOylation, etc.) of specific residues. Development of strategies to modulate transient multienzyme and/or enzyme-protein interactions may represent a novel and promising therapeutic approach for treatment of diseases involving dysregulation of glutamate metabolism.