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Dev Neurosci. 1998;20(4-5):434-43.

15N-NMR spectroscopy studies of ammonia transport and glutamine synthesis in the hyperammonemic rat brain.

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Department of Internal Medicine, Yale University School of Medicine, New Haven, Conn., USA.


Ammonia transport and glutamine synthesis were studied in the hyperammonaemic rat brain in vivo using 15N-NMR spectroscopy at a plasma ammonia level of approximately 0.39 mM raised via an intravenous [15N]-ammonium acetate infusion. The initial slope of the time course of the summed cerebral 15N-labelled metabolites was used to determine the rate of ammonia net transport during hyperammonemia as 0.13 +/- 0.02 micromol/min/g (mean +/- SD; n = 5). Based on the total accumulation of glutamine and the 1:2 stoichiometric relationship between fluxes of four-carbon skeletons and nitrogen atoms, the rate of de novo glutamine synthesis through anaplerosis and subsequent glutamate dehydrogenase action was calculated to be 0.065 +/- 0.01 micromol/min/g. The rate of total glutamine synthesis was estimated to be 0.20 +/- 0.06 micromol/min/g (n = 5) by fitting the [5-15N]glutamine time course to a previously described model of glutamate-glutamine cycling between astrocytes and neurones. A large dilution was also observed in [2-15N]glutamine, which supports the glutamate-glutamine cycle as being an important pathway for neuronal glutamate repletion in vivo.

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