The acute action of ammonia on rat brain metabolism in vivo

R. A. Hawkins, A. L. Miller, R. C. Nielsen, R. L. Veech

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196 Scopus citations

Abstract

Acute NH4+ toxicity was studied by using a new apparatus that removes and freezes the brains of conscious rats within 1 sec. Brains were removed and frozen 5 min after intraperitoneal injection of ammonium acetate (2 to 3 min before the onset of convulsions). Arterial [NH4+] rose from less than 0.01 to 1.74 mM at 4 to 5 min. The concentrations of all glycolytic intermediates measured, except glucose 6 phosphate, were increased by the indicated percentage above the control value as follows: glucose (by 41%), fructose 1,6 diphosphate (by 133%), dihydroxyacetone phosphate (by 164%), α glycerophosphate (by 45%), phosphoenolpyruvate (by 67%) and pyruvate (by 26%). Citrate and α oxoglutarate concentrations were unchanged and that of malate was increased (by 17%). Adenine nucleotides and P(i) concentrations were unchanged but the concentration of creatine phosphate decreased slightly (by 6%). Brain [NH4+] increased from 0.2 to 1.53 mM. Net glutamine synthesis occurred at an average rate of 0.33 μmol/min per g. The rate of brain glucose utilization was measured in vivo as 0.62 μmol/min per g in controls and 0.81 μmol/min per g after NG4+ injection. The arteriovenous difference of glucose and O2 increased by 35%. No significant arteriovenous differences of glutamate or glutamine were detected. Thus, although much NG4+ was incorporated into glutamine the latter was not rapidly released from the brain to the circulation. Plasma [K+] increased from 3.3 to 5.4 mM. The results indicate that NH4+ stimulates oxidative metabolism but does not interfere with brain energy balance. The increased rate of oxidative metabolism could not be accounted for only on the basis of glutamine synthesis. It is suggested that increased extracellular [NH4+] and [K+] decreased the resting transmembrane potential and stimulated Na+, K+ stimulated adenosine triphosphatase activity thus accounting for the increased metabolic rate.

Original languageEnglish (US)
Pages (from-to)1001-1008
Number of pages8
JournalBiochemical Journal
Volume134
Issue number4
DOIs
StatePublished - 1973

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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