Influence of Phenobarbital Anesthesia on Carbohydrate and Amino Acid Metabolism in Rat Brain

Abstract

Experiments were undertaken to study whether phenobarbital decreases cerebral O2 utilization and glucose consumption by proportional amounts or decreases glycolytic rate to such an extent that endogenous substrates must be mobilized to cover oxidative requirements. Concentrations in brain tissue of glycolytic metabolites, citric acid cycle intermediates, associated amino acids (glutamate, aspartate, alanine, .gamma.-aminobutyric acid and glutamine) and ammonia were measured 2, 30 or 180 min after administration of phenobarbital, 150 mg/kg, to rats. Values were compared with those obtained from animals anesthetized with NO2 70%. In all phenobarbital-treated groups, there was accumulation of G-6-P, with depletion of fructose-1,6-diphosphate and subsequent glycolytic metabolites. After 30 min, phenobarbital decreased concentrations of citric acid cycle intermediates (citrate, .alpha.-ketoglutarate, fumarate, malate and [calculated] oxaloacetate], as well as glutamate and increased aspartate concentration. Phenobarbital apparently retards glycolytic flux at the phosphofructokinase step, and endogenous substrates may be mobilized from existing carbohydrate and amino acid pools. The size of the pool of carbohydrate substrates did not decrease further when phenobarbital anesthesia was prolonged from 30 to 180 min; none of the phenobarbital-treated groups showed a decrease in the amino acid pool, and there was no increase in ammonia concentration. There was no indication that endogenous substrates are continuously consumed or that phenobarbital leads to oxidative deamination of amino acids.