Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Brain Signaling of Indispensable Amino Acid Deficiency

Version 1 : Received: 20 November 2021 / Approved: 23 November 2021 / Online: 23 November 2021 (14:51:31 CET)

A peer-reviewed article of this Preprint also exists.

Gietzen, D.W. Brain Signaling of Indispensable Amino Acid Deficiency. J. Clin. Med. 2022, 11, 191. Gietzen, D.W. Brain Signaling of Indispensable Amino Acid Deficiency. J. Clin. Med. 2022, 11, 191.


Our health requires continual protein synthesis for maintaining and repairing tissues. For protein synthesis to function, all the essential (indispensable) amino acids (IAA) that must be available in the diet, along with those AAs that the cells can synthesize, the dispensable amino acids. Here we review studies that have shown the location of the detector for IAA deficiency in the brain, specifically for recognition of IAA deficient diets (IAAD diets) in the anterior piriform cortex (APC), with subsequent responses in downstream brain areas. The APC is highly excitable, uniquely suited to serve as an alarm for reductions in IAAs. With a balanced diet, these neurons are kept from over-excitation by GABAergic inhibitory neurons. Because several transporters and receptors on the GABAergic neurons have rapid turnover times, they rely on intact protein synthesis to function. When an IAA is missing, its unique tRNA cannot be charged. This activates the enzyme General Control Nonderepressible 2 (GCN2) that is important in the initiation phase of protein synthesis. Without the inhibitory control supplied by GABAergic neurons, excitation in the circuitry is free to signal an urgent alarm. Studies in rodents have shown rapid recognition of IAA deficiency by quick rejection of the IAAD diet.


protein synthesis initiation; neural signaling; Anterior Piriform Cortex; transfer RNA; GCN2


Biology and Life Sciences, Food Science and Technology

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