Cerebral energy reserves and glycolysis in neural tissue of 6‐aminonicotinamide‐treated mice

Cerebral energy metabolism was studied in brains of mice treated with the nicotinamide analog, 6‐aminonicotinamide (6‐AN), which is converted to a potent inhibitor of 6‐phosphogluconate dehydrogenase in viro. Six hours after administration of 6‐AN, the level of cerebral 6‐phosphogluconate was increased at least 170‐fold, whereas substrates for other NADP +‐dependent dehydrogenases either did not change or increased only slightly. Large increases in 6‐phosphogluconate were observed in the cerebral cortex, three layers of the cerebellum, and the dorsal column and anterior horn regions of the spinal cord after administration of 6‐AN. Thus, glucose was metabolized via the oxidative enrymes of the pentose phosphate pathway in a wide variety of neuronal structures in vivo. Highest concentrations of 6‐phosphogluconate were observed in the cerebellar molecular layer. Energy use rates and glycolysis were studied by measuring the disappearance of the major energy reserves during periods of anoxic‐ischemia imposed on cerebral tissue of 6‐AN‐treated mice. Production of lactate and utilization of glycogen during anoxic‐ischemia were reduced in brain of 6‐AN‐treated mice, which is in accord with the suggestion that glycolysis is inhibited in cerebral tissue of 6‐AN‐treated animals. Levels and ratios of pyridine nucleotides in cerebral tissue were not altered by 6‐AN treatment. From changes in levels of ATP, phosphocreatine, glucose, and glycogen in brain during ischemia, the rate of energy use was calculated to be 21.7 mmol · kg wet tissue−1 · min−1, which was not significantly different from that observed in normal adult mouse brain. Therefore, despite an apparent slowing of hexose utilization in cerebral tissue 6‐AN‐treated mice, normal cerebral energy use was maintained during the initial period of anoxic‐ischemia.