Differential roles of alanine in GABAergic and glutamatergic neurons

Studies in different preparations of neurons and astrocytes of alanine transport and activities of its metabolizing enzyme alanine aminotransferase have led to the proposal that this amino acid is preferentially synthesized in astrocytes and transferred from the astrocytic to the neuronal compartment. From a functional point of view this may well be the case in a GABAergic synapse since theoretically alanine can be utilized as a metabolic fuel in GABAergic neurons where the GABA shunt is operating. Thus, a metabolic scheme is proposed, according to which alanine catabolism is coupled to the TCA cycle where the GABA shunt replaces the alpha-ketoglutarate dehydrogenase/succinyl CoA synthetase reactions. In a glutamatergic synapse in which the large demand for synthesis of neurotransmitter glutamate leads to a large production of ammonia, it is possible that alanine could play a completely different role. Hence, experimental evidence is reviewed suggesting that alanine may serve as a carrier of ammonia nitrogen from the neuronal compartment to the astrocytic compartment using a flux of lactate in the opposite direction to account for transfer of the C-3 carbon skeleton.