Abstract
Rats were given intravenous ^15^NH~4~^+^ infusion at a rate of 2.2 or 5.5 mmol/h/kg body wt to induce hyperammonemia, as animal models of hepatic encephalopathy. Its effect on cerebral amino acid metabolism was studied in vivo by ^15^N NMR spectroscopy at 20.27 MHz for ^15^N. Cerebral [Ξ³β^15^N]glutamine (present at a tissue concentration of 4β9 ΞΌmol/g) and [Ξ±β^15^N]glutamate/glutamine (6 ΞΌmol/g) were clearly observed in living rats within 9β18 min. In portacavalβshunted rats, final cerebral [Ξ³β^15^N]glutamine concentrations were higher than those in controls after the same infusion period, presumably because decreased ^15^NH removal in the liver led to increased ^15^NH~3~ diffusion into the astrocytes. In control rats, cerebral [Ξ³β^15^N]glutamine pool increased at a rate of 1.7 ΞΌmol/h/g when blood ammonia concentration was 0.8 mM. ^15^N enrichment in Ξ³β^15^N was 71%. From these observations, in vivo activity of glutamine synthetase in rat brain was estimated to be 3.5 ΞΌmol/h/g. Comparison with reported optimum in vitro activity suggests that in situ concentrations of some substrates and cofactors limit the activity of glutamine synthetase in vivo.