STEADY-STATE IN-VIVO GLUTAMATE-DEHYDROGENASE ACTIVITY IN RAT-BRAIN MEASURED BY N-15 NMR

The in vivo activity of glutamate dehydrogenase (GDH) in the direction of reductive amination was measured in rat brain at steady-state concentrations of brain ammonia and glutamate after intravenous infusion of the substrate (NH4+)-N-15. The in vivo rate was determined from the steady-state fractional. N-15 enrichment of brain ammonia, measured by selective observation of (NH4+)-N-15 protons in brain extract by H-1 -N-15 heteronuclear multiple-quantum coherence transfer MMR, and the rate of increase of brain [N-15]glutamate and [2-N-15]glutamine measured by N-15 NMR. The in vivo GDH activity was 0.76-1.17 mu mol/h/g at a brain ammonia concentration of 0.87 +/- 0,18 mu mol/g, and 1.1-1.2 mu mol/h/g at 1.0 +/- 0.17 mu mol/g. Comparison of the observed in. vivo GDH activity with the in vive rates of glutamine synthesis and of phosphate-activated glutaminase suggests that, under mild hyperammonemia, GDH-catalyzed de novo synthesis can provide a minimum of 19% of the glutamate pool that is recycled from neurons to astrocytes through the glutamate-glutamine cycle.