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Neuronal Glutamine Utilization: Glutamine/Glutamate Homeostasis in Synaptosomes
Author(s) -
Erecińska Maria,
Zaleska Malgorzata M.,
Nelson David,
Nissim Itzhak,
Yudkoff Marc
Publication year - 1990
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1990.tb04911.x
Subject(s) - glutamate receptor , glutamine , glutamine synthetase , homeostasis , biochemistry , synaptosome , chemistry , neuroscience , biology , microbiology and biotechnology , amino acid , in vitro , receptor
The synaptosomal metabolism of glutamine was studied under in vitro conditions that simulate depolarization in vivo. With [2‐ 15 N]glutamine as precursor, the [glutamine]i was diminished in the presence of veratridine or 50 m M KCl, but the total amounts of [ 15 N]glutamate and [ 15 N]aspartate formed were either equal to those of control incubations (veratridine) or higher (50 m M [KCl]). This suggests that depolarization decreases glutamine uptake and independently augments glutaminase activity. Omission of sodium from the medium was associated with low internal levels of glutamine which indicates that influx occurs as a charged Na + ‐amino acid complex. It is postulated that a reduction in membrane potential and a collapse of the Na + gradient decrease the driving forces for glutamine accumulation and thus inhibit its uptake and enhance its release under depolarizing conditions. Inorganic phosphate stimulated glutaminase activity, particularly in the presence of calcium. At 2 m M or lower [phosphate] in the medium, calcium inhibited glutamine utilization and the production of glutamate, aspartate, and ammonia from glutamine. At a high (10 m M ) medium [phosphate], calcium stimulated glutamine catabolism. It is suggested that a veratridine‐induced increase in intrasyn‐aptosomal inorganic phosphate is responsible for the enhancement of flux through glutaminase; calcium affects glutaminase indirectly by modulating the level of free intramitochondrial [phosphate]. Because phosphate also lowers the K m of glutaminase for glutamine, augmentation of the amino acid breakdown may occur even when depolarization lowers [glutamine] i . Reducing the intrasynaptosomal glutamate to 26 nmol/mg of protein had little effect on glutamine catabolism, but raising the pH to 7.9 markedly increased formation of glutamate and aspartate. It is concluded that phosphate and H + are the major physiologic regulators of glutaminase activity.