Chapter 21: Glutamate as an energy substrate for neuronal-astrocytic interactions

Abstract

This chapter discusses the role of glutamate as a metabolic substrate. Glutamate is the most plentiful amino acid and the major excitatory neurotransmitter in adult central nervous system (CNS). Glutamate participates in the synthesis of proteins, peptides and fatty acids, and in the control of osmotic or anionic balance. It is a constituent of at least two important co-factors, glutathione and folic acid; it contributes along with glutamine to the regulation of ammonia levels, and it serves as precursor for GABA and various tricarboxylic acid (TCA) cycle intermediates. Glutamate is released from neurons in large amounts. Uptake studies demonstrates that both neurons and astrocytes take up glutamate. The uptake of glutamate into astrocytes represents a net transfer of carbon skeleton from the neurons to astrocytes. There are three probable roles for this uptake process: (1) to remove the glutamate from extracellular space and synaptic clefts as a means of termination of the transmitter activity; (2) to form glutamine during the detoxification of ammonia and (3) to serve as a metabolic substrate for astrocytes. Metabolic studies have shown that, a part of the glutamate taken up by astrocytes is metabolized to CO2 and another part to glutamine, the latter of which then can be returned to neurons as a precursor for glutamate and GABA. Glutamate exerts a regulatory effect on glycogen metabolism in astrocytes and also affects glucose utilization in astrocytes. Glutamate also plays an important role in the pathogenesis of various neurologic diseases and insult.