Metabolism Matters – the Role of Glutamate/glutamine Metabolism in Brain Function and Disease

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The central role of metabolism is still stressed in biochemistry course but in recent studies of brain function and pathogenesis metabolic processes are overshadowed by the reigning views of the brain as an information processor supported primarily by small fluctuations in neurotransmitter and electrical signaling. However, understanding neural function requires that close attention be paid to key findings over the last 25 years that build on and extend a century of physiological biochemistry research and place brain metabolism squarely in the ongoing effort to understand neural health and disease. Glutamate and GABA, amino acids serving as both neurotransmitters and substrates for essential metabolic networks (also involving other amino acids such as glutamine and aspartate) linking across populations of neuronal and glial cells.

Alterations in enzymatic reactions or in cell transporter activities integral to the metabolic cycling of the glutamate system results in impaired brain function. Glutamate metabolism also links cellular metabolic reactions with energy production in the mitochondria and mitochondrial dysfunction has been identified as contributory to many brain pathologies and has been invoked as a cause of cognitive function in healthy aging. Imaging studies have found that levels of glutamate and GABA have a significant impact on brain network organization and plasticity. Glutaminases may play a key role in the pathogenesis, and treatment, of neurodegenerative disorders and brain cancer.

This symposium reviews elements of the current understanding of the role of brain glutamate/glutamine metabolism in brain function and in disease with the goal of identifying outstanding questions in the field and potential new treatment strategies based on this new understanding. In doing so, the symposium honors the ongoing contributions of Arthur J.L. Cooper, who in his more than 40 year career as an enzymologist focusing on neurochemical problems has made and continues to make significant advances to this fundamentally important area of research among many others.

The symposium is sponsored by the James S. McDonnell Foundation, and is consistent with the Foundation’s goals of identifying and supporting research leading to a deeper understanding of human cognition and brain diseases, especially brain cancer, and to applying research knowledge to the development of improved treatments for cognitive disorders and brain cancer.