Redox dependence and compartmentation of [13C]pyruvate in the brain of deuterated rats bearing implanted C6 gliomas

We investigated the redox dependence and compartmentation of the pyruvate pool in the brain of partially deuterated rats bearing C6 gliomas. Adult male Wistar rats implanted with C6 cells drunk (H2O)-H-2 (50% v/v) or tap water for 9 days before they were infused with solutions containing [1-C-13]glucose and [2-C-13]pyruvate or [U-C-13(3)]lactate. Their brains were fixed with high-power focused microwaves and biopsies prepared from the contralateral, ipsilateral, and tumor regions. C-13 NMR analysis of the extracts allowed the determination of the relative amounts of [C-13]lactate isotopomers derived from infused glucose or monocarboxylates. The relative amounts of [3-C-13]lactate derived from glucose to the [2-C-13] or [U-C-13(3)]lactate isotopomers derived from monocarboxylates decreased in the order contralateral > ipsilateral > tumor regions, revealing a progressive reduction in glycolysis for regions containing increasing endogenous lactate concentrations. Cortical astrocytes depicted similar reductions in glycolysis when incubated with [1,2-C-13(2)]glucose and increasing concentrations of [3-C-13]lactate. Deuterated animals bearing C6 tumors, infused with [1-C-13]glucose and [2-C-13]pyruvate, showed different deuterium enrichments in the methyl groups of cerebral [3-C-13] and [2-C-13]lactate, revealing a slow mixing of the [3-C-13] and [2-C-13]pyruvate precursors in the H-2 exchange timescale of their methyl groups. Together, these evidences reveal the role of the redox state of the pyruvate pool derived from monocarboxylates in the modulation of cerebral glycolytic flux in vivo and in vitro.