Regulation of Glycolysis in Brain, in Situ, during Convulsions

Abstract

Abstract The concentrations of metabolites, including glucose, glycogen, glycolytic intermediates, adenine nucleotides, phosphates, amino acids, and citrate, in mouse brain in situ were measured from 15 to 180 sec after exposure of mice to the convulsant, Indoklon (bis(2,2,2-trifluoroethyl) ether). An increase in glycolytic flux of at least 3 times the basal rate was estimated for the brain in the convulsive state. During the period of hyperactivity, new steady state levels were established for several metabolites. In the transition, the concentrations of glucose and hexose monophosphates in the brain decreased. Coincident with these decreases, the concentration of fructose 1,6-diphosphate increased rapidly but transiently. The concentration of cerebral glycogen was unchanged during the first 30 sec, decreased about 20% during the next min, and then remained constant. Lactate accumulated throughout the period of convulsion. At the initiation of convulsion, the concentration of creatine phosphate fell precipitously to half its original value. The decrease in adenosine triphosphate was relatively small. Correspondingly, the concentrations of ADP, AMP, and inorganic phosphate in the brain increased rapidly with the induction of hyperactivity. The concentrations of citrate, glutamate, and aspartate did not change significantly. The level of proline was lowered during the convulsion. With the induction of convulsions and concomitant with the increased rate of glycolysis, the enzymes phosphofructokinase and hexokinase were coordinately activated. These two enzymatic sites represent the major control points of glycolysis in cerebral tissue in vivo. The ability of the brain to adjust to a new steady state following an increase in glycolytic rate, as well as its ability to maintain adequate supplies of energy reserves and oxygen, serves to distinguish the convulsive from the ischemic condition.