Glutamine and alpha-ketoglutarate uptake and metabolism by nerve terminal enriched material from mouse cerebellum

In order to provide evidence relevant to the hypothesis that nonsynaptically derived alpha-ketoglutarate serves as a metabolic precursor of the neurotransmitter pools of glutamate and GABA the uptake and metabolism of alpha-ketoglutarate by nerve terminal enriched material was studied and compared to corresponding data for glutamine. Both alpha-ketoglutarate and glutamine were transported across the cell membrane by high affinity and low affinity carriers. Under conditions prevailing in vivo alpha-ketoglutarate probably is transported primarily by its high affinity carrier, whereas gluatmine should be transported primarily by one or more low affinity carriers. Based upon reciprocal uptake inhibition experiments glutamine appeared to be transported by the alanine preferring system, and to a lesser extent by the basic amino acid and large neutral amino acid carriers. A comparison of the rate of uptake by different cellular preparations enriched in either nerve terminals or cell bodies indicated that alpha-ketoglutarate is transported selectively by nerve terminals. Both substrates were rapidly converted to glutamate; however, glutamine was more readily metabolized to GABA. The results of our study are consistent with the concept that both glutamine and alpha-ketoglutarate derived from extra-neuronal sources are taken up by nerve terminals and utilized to replenish the neurotransmitter pools of glutamate and GABA.