Glutamic acid is an amino acid with multiple biological roles. In the animal world, it links the metabolism of carbon and nitrogen and, depending on the need, serves either as a source of energy or as a reservoir of ammonia. It is also an important component in the synthesis of both small (glutathione) and large (peptides and proteins) molecules. In the CNS glutamate has two additional functions: it is a neurotransmitter in its own fight and a precursor of 7-aminobutyric acid (GABA). The purpose of this article is to discuss the metabolism of glutamate and evaluate its role in mammalian brain. The most direct approach is through a critical analysis of the metabolic pathways involved, together with an account of glutamate distribution and transport. Because of the range and complexity of the issues raised, as well as our primary emphasis on its metabolic functions, we will not discuss glutamate as a neurotransmitter.

This review is not intended to be a comprehensive and entirely objective account of the literature. Rather it expresses the views and prejudices of the authors. However to balance these tendencies and to provide the evidence on which our opinions are based, the article relies heavily on original publications by other authors with relatively few references to previous reviews. Moreover, to provide a fresh outlook on the subject, we have identified inconsistencies in the literature and where possible sought feasible explanations for seemingly contradictory observations and hypotheses. This approach, which in places challenges some areas of orthodox dogma, will we hope be thought-provoking and lead to the development of new concepts and the means to test them.