Fig. 5: Simplified schematic depicting the route of [1-13C]pyruvate (1-Pyr) to [4-13C]oxaloacetate (4-OAA) to yield [13C]bicarbonate from PEPCK flux.

Pyruvate carboxylation takes place in the mitochondrion and transporters of the malate-aspartate shuttle facilitate export to the cytoplasm. Label exchange of malate from the 1- to 4-position is mediated by fumarase (FH). Reversible reactions and transport steps between PC and PEPCK are indicated as unidirectional for simplicity and to illustrate label flow. The main route to cytoplasmic 4-OAA is indicated in bold. MPC1, mitochondrial pyruvate carrier-1; GOT, glutamate oxaloacetate aminotransferase; MDH, malate dehydrogenase; AGC2, aspartate-glutamate antiporter; OGC, 2-oxoglutarate/malate carrier; PEPCKm, mitochondrial PEPCK; PEPCKc, cytoplasmic PEPCK.