The effect of inhibition of hexosemonophosphate shunt on the metabolism of glucose and function in rat brain in vivo.

Rats treated 4 hr previously with 6-aminonicotinamide showed a twenty-four fold increase of [14C]phosphogluconate in the adult brain at 30 min after injection of [U-14C]glucose indicating a blockade of the hexosemonophosphate shunt. There was a significant increase in the 14C-content of glucose and glucose-6-phosphate, and a decrease in that of amino acids. [14C]Phosphoglycerate content showed no consistent change after 6-aminonicotinamide treatment. The concentration of glucose and glucose 6-phosphate increased significantly without a significant change in the lactate pool in the brain of 6-aminonicotinamide treated rats. The rate of utilization of glucose in the brain of control rats was 0.73 mumol/min per g of brain. It decreased by 16% in rats treated with 6-aminonicotinamide; the results suggested that both glycolysis and pyruvate oxidation were affected. The amount of glucose utilized in the brain by the hexosemonophosphate shunt was approximately 0.0093 mumol/min per g of brain, i.e. 1.3% of the total rate of utilization of glucose. The observed changes were not due to hypothermia. The rate of glucose utilization was higher in animals exposed to higher ambient temperature and to stress caused by handling. The results were explained by postulating a role for the hexosemonophosphate shunt in providing neurotransmitter amino acids glutamate and gamma-aminobutyrate, and interdependence of brain function and glucose utilization.