Regulation of thiols in the brain. 3. Glucose metabolism in the cytoplasmic fraction of rat brain during stimulation of the hexose monophosphate shunt in vitro.

Abstract

<h2>Abstract</h2> The production of lactic acid by the cytoplasmic fraction of the brain cortex decreased by 50% in the presence of 0–5 mm-NADP+ and 2–5 mm-oxidized glutathione. Simultaneously 38% of the glucose, metabolized at an unchanged rate, entered the hexose monophosphate shunt, as was indicated by the increase in concentration of reduced glutathione due to the utilization (by glutathione reductase) of NADPH produced in the shunt. This competition between glycolysis and the hexose monophosphate shunt was not observed after the addition of exogenous hexokinase or glucose 6-phosphate instead of glucose. The experiments on the effects of different concentrations of glucose and glucose 6-phosphate on thiols and lactic acid formation indicated that hexokinase may influence the competition between the hexose monophosphate shunt and glycolysis by limiting the concentration of glucose 6-phosphate. Under experimental conditions the production of thiol groups reached the highest velocity in much lower concentrations of glucose 6-phosphate than did lactic acid production. The above results, together with the previously found increase in concentration of oxidized glutathione and activity of glucose 6-phosphate dehydrogenase under hypoxia, suggested that the increased flux of glucose 6-phosphate through the hexose monophosphate shunt as a result of competition of the shunt with glycolysis, may bypass phosphofructokinase, which was reported not to be stimulated by hypoxia.