Chapter 6 Synthesis of glutamate and its regulation

Abstract

Publisher Summary Glutamate (Glu) is a key substance in the brain, being involved in metabolism, pathology, and neurotransmission and is an essential source of energy. It is involved in the synthesis of proteins and peptides, as well as other compounds and in the detoxication of ammonia in the brain. Important regulatory processes are cellular uptake mechanisms for Glu and precursor substances, compartmentalization and enzymes involved in the synthesis, and degradation of Glu. It is now generally accepted that the Glu–Gln cycle has an important function in the brain. However, the cycle does not operate in a stoichiometric manner, and Glu and Gln are taken up and metabolized by both cultured astrocytes and neurons. Glutamine (Gln) and glucose-derived 2-oxoglutarate (2-OG) are considered to be the main precursors of metabolic and neurotransmitter Glu both in vitro and in vivo . The chapter discusses these substrates and the corresponding enzymes involved in Glu formation. However, as Gln appears to be the preferred precursor for transmitter Glu, the key enzyme in this reaction, phosphate activated glutaminase (PAG) (Gln amidohydrolase)—also called phosphate dependent glutaminase—is described in the chapter.