Two-compartment model describing the incorporation of label from [3-13C]lactate into the brain glutamate and glutamine pools. Left, Neuronal compartment; right, astroglial compartment. Lac, Lactate; Glc, glucose; Pyr, pyruvate; AcCoA, acetyl coenzyme A; OAA, oxaloacetate; αKG, α-ketoglutarate; Glu, glutamate; Gln, glutamine; Asp, aspartate; Vin, influx of lactate; Vout, efflux of lactate; CMRglc, glucose consumption; VPDHn, neuronal flux through the pyruvate dehydrogenase; VPDHg, astroglial flux through the pyruvate dehydrogenase; VTCAn, neuronal TCA cycle rate; VTCAg, astroglial TCA cycle rate; VPC, flux through the pyruvate carboxylase; Vcycle, glutamate/glutamine cycle flux; VXn, mitochondrial/cytosolic glutamate/α-ketoglutarate exchange rate in neurons; VXg, mitochondrial/cytosolic glutamate/α-ketoglutarate exchange rate in astrocytes. In our experiment, 13C-labeled lactate cross the blood–brain barrier back and forth through the monocarboxylate transporters (KT, VMAX) and arrives at the C3 of the lactate/pyruvate pool (regrouped as a unique pool because of the very fast exchange between them through the lactate dehydrogenase), where the label enters the TCA cycle via pyruvate carboxylase or pyruvate dehydrogenase reaction. It is ultimately detected at the first turn of the TCA cycle in the C4 position of glutamate and glutamine then, after label scrambling by the TCA activity, on the C2 and C3 positions of glutamate and glutamine.