Molecular Arrangement for Physiological Action of Glutamic Acid and γ-Aminobutyric Acid

Abstract

On combination of the amino group of glutamate or γ-aminobutyric acid (GABA) with a receptor site, RN, the steric influence of the α-carboxyl or γ-hydrogen on the adjacent carbon directs that this site in the receptor separate from surrounding protein structures. In this manner a space may be created in the membrane which measures 5.70–6.30 Å in the case of glutamate and 3.70–4.50 Å for GABA. These values are in good agreement with the diameter of hydrated sodium ions (4.80–5.12 Å) and chloride ions (3.32–3.86 Å). A selective increase in the permeability of the membrane towards sodium or chloride causes, respectively, excitation or inhibition in neurons. The pharmacological action of certain ω-amino acids may therefore be associated with a conformational change in the membrane, required to accommodate the space-filling configuration around the carbon, adjacent to nitrogen. In order that the steric influence of a substituent on this carbon exclusively directs the dimensions of the space to be formed, and for several other reasons, the amino acids probably adopt a specific molecular conformation when interacting with the receptor.