Effects of Hypercarbia and Porta-Caval Shunting on Amino Acids and High Energy Phosphates of the Rat Brain: a ¹H and ³¹P NMR Study

Abstract

Intracellular acidosis and hyperammonemia are associated with numerous metabolic encephalopathies. Conditions such as cerebral hypoxia, ischemia, seizures, and hypercarbia are accompanied by marked increases in intracellular [H⁺] and [NH ⁺₄ ]. Changes in either [H⁺] or [NH ⁺₄ ] lead to changes in the concentrations of cerebral amino acids and metabolic intermediates of both the glycolytic and TCA cycle (Miller et al, 1975; Cooper and Lai, 1987). The mechanism(s) involved and the site(s) of regulation of substrate flux by changes in the concentrations of these ions is not known with certainty. It is known that nearly all encephalopathies that involve an increase in ammonium ion concentration are accompanied by a decrease in the concentration of cerebral glutamate and an increase in glutamine. Hypercarbic acidosis also results in a decrease in the concentration of glutamate in rat brain and an increase of glutamine and ammonium ion (Folbergrová et al, 1972; Miller et al, 1975). It is important to note that neither acute hyperammonemia (Fitzpatrick et al, 1989) nor porta-caval shunting affects intracellular pH (Fitzpatrick et al, 1988); therefore, changes in pH_i cannot be responsible for the decrease in glutamate, observed in response to elevated ammonium ion.