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

Dev Neurosci. 1998;20(4-5):434-43. doi: 10.1159/000017341.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetates / pharmacology
  • Ammonia / blood
  • Ammonia / metabolism*
  • Animals
  • Biological Transport / physiology
  • Brain / metabolism*
  • Glutamic Acid / metabolism
  • Glutamine / biosynthesis*
  • Magnetic Resonance Spectroscopy*
  • Male
  • Models, Biological
  • Nitrogen Isotopes
  • Osmolar Concentration
  • Rats
  • Rats, Sprague-Dawley


  • Acetates
  • Nitrogen Isotopes
  • Glutamine
  • Glutamic Acid
  • Ammonia
  • ammonium acetate