ALTERNATIVE PATHWAYS OF GLUCOSE-UTILIZATION IN BRAIN - CHANGES IN THE PATTERN OF GLUCOSE-UTILIZATION IN BRAIN DURING DEVELOPMENT AND THE EFFECT OF PHENAZINE METHOSULFATE ON THE INTEGRATION OF METABOLIC ROUTES

The activities of alternative pathways of glucose metabolism in developing rat brain were evaluated by measurement of the yields of 14CO2 from glucose labeled with 14C on carbons 1, 2, 3 + 4, 6 and uniformly labeled glucose, from the detritiation of [2-3H]glucose and from the incorporation of 14C from specifically labeled glucose into lipids by brain slices from cerebral hemispheres and cerebellum. The glycolytic route and tricarboxylic acid cycle (14CO2 yield from carbons 3, 4, and 6 of glucose) increased during development. The flux through the glutamate-γ-aminobutyric route (14CO2 yield from carbon 2-carbon 6 of glucose) also showed an increase with development. In contrast, the proportion of glucose metabolized via the pentose phosphate pathway was markedly decreased as development progressed. The artificial electron acceptor, phenazine methosulfate, was used as a probe to investigate the effect of alterations in the redox state of NADP+ NADPH couple on a number of NADP-linked systems in developing brain. Phenazine methosulfate produced a massive (20- to 50-fold) stimulation of the pentose phosphate pathway, in contrast, the incorporation of glucose carbon into fatty acids and flux through the glutamate-γ-aminobutyrate shunt were sharply decreased. The effects of phenazine methosulfate on the incorporation of glucose into glyceride glycerol, on the flux of glucose through the pyruvate dehydrogenase reaction and tricarboxylic acid cycle, all processes linked to the NAD+ NADH couple, appeared to be minimal in the brain at the stages of development studied, i.e., 1, 5, 10, 20 days, and in the adult rat. The significance of the massive reserve potential of the pentose phosphate pathway in the developing brain is discussed. © 1979.