Alternative Pathways of Glucose Utilization in Brain; Changes in the Pattern of Glucose Utilization in Brain Resulting from Treatment of Rats with 6‐Aminonicotinamide

Abstract

The effect of 6-aminonicotinamide (6AN) treatment on the activities of alternative pathways of glucose metabolism in 20-day-old rat brain was evaluated; measurements of yields of 14CO2 from glucose labeled with 14C on carbons 1, 2, 3 + 4 or 6 and uniformly labeled glucose, and from the incorporation of 14C from specifically labeled glucose into lipids by brain slices from cerebral hemispheres and cerebellum were used. At the highest dose of 6AN used (35 mg/kg body wt) there was a significant decrease in the 14CO2 yields via the pentose phosphate pathway, the glycolytic route, tricarboxylic acid (TCA) cycle and via the glutamate-GABA pathway. Giving a graded series of doses (20-35 mg 6AN/kg body wt) revealed a hierarchy of responses in which the pentose phosphate pathway, lactate, glyceride-glycerol and fatty acid formation were most sensitive; this was followed, in sequence, by the pyruvate dehydrogenase reaction, the glutamate-GABA route and the TCA cycle. The nature of the blocks in the various pathways was examined by the use of metabolite profiles.