Alternative Pathways of Glucose Utilization in Brain: Changes in the Pattern of Glucose Utilization and of the Response of the Pentose Phosphate Pathway to 5‐Hydroxytryptamine During Aging

Abstract

The oxidation of differentially labeled glucose, pyruvate and glutamate in brain slices from rats aged 20 days to 26 mo. was studied and the partition of the glucose used into the glycolytic-tricarboxylic acid cycle pathway, the pentose phosphate pathway and the glutamate-GABA shunt was calculated. Over the time range 4-26 mo., there is an .apprx. 20% decrease in the production of CO2 via the glycolytic-tricarboxylic acid cycle route, as there is in the rate of glucose phosphorylation. The glutamate-GABA pathway falls by about 50% over this same time span. The broad activity of the pentose phosphate pathway falls rapidly and cannot be detected in the brains of rats aged 18 mo. or more, whereas the fully stimulated pathway, i.e., in the presence of the artificial electron acceptor phenazine methosulfate, declines only marginally over this period, falling sharply only after 23 mo. The pentose phosphate pathway is stimulated by the presence of 5-hydroxytryptamine and this stimulation appears to increase with age.