Redox Dependence and Compartmentation of [13C]Pyruvate in the Brain of Deuterated Rats Bearing Implanted C6 Gliomas

Tiago Brandao Rodrigues¹, Pilar Lopez-Larrubia¹, Sebastin Cerdn¹

We investigated the redox dependence and compartmentation of the pyruvate pool in the brain of partially deuterated rats bearing C6 gliomas. The rats were infused with [1-¹³C]glucose and [2-¹³C]pyruvate or [U-¹³C₃]lactate. The relative amounts of [3-¹³C]lactate derived from glucose to the [2-¹³C] or [U-¹³C₃]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. Deuterated animals bearing C6 tumors, infused with [1-¹³C]glucose and [2-¹³C]pyruvate, showed different deuterium enrichments in the methyl groups of cerebral [3-¹³C] and [2-¹³C]lactate, revealing a slow mixing of the [3-¹³C] and [2-¹³C]pyruvate precursors in the ²H exchange timescale of their methyl groups.