Fig. 1: Carbon flow from [1-¹³C]pyruvate through TCA cycle and GNG in liver and representative evolution of the ¹³C MR spectra measured in the rat liver.

a ¹³C labeling of injected pyruvate is converted to C1 of lactate and alanine through lactate dehydrogenase (LDH) and alanine aminotransferase (ALT), respectively. Decarboxylation of [1-¹³C]pyruvate through pyruvate dehydrogenase (PDH) yields ¹³CO₂ and acetyl-CoA. The released ¹³CO₂ is interconverted with bicarbonate (H¹³CO₃) through carbonic anhydrase. Pyruvate carboxylase (PC) converts [1-¹³C]pyruvate to [1-¹³C]oxaloacetate (OAA). C4 of OAA is labeled after conversion to fumarate and 1,4-label scrambling. OAA contributes to citrate formation in condensation with acetyl-CoA and is also converted to phosphoenolpyruvate (PEP) through phosphoenolpyruvate-carboxykinase (PEPCK). PEP contributes to the production of glucose via an eight-step pathway. 3-mercaptopicolinic acid (3-MPA) inhibits glucose synthesis by blocking conversion of OAA to PEP. *¹³CO₂ indicates labeled CO₂/bicarbonate from PDH flux; **¹³CO₂—from PEPCK flux; Spectra in fed (b) and fasted (c) animals were measured every ~3 s following the injection of 0.023 ± 0.002 mmol/kg HP [1-¹³C]pyruvate in the femoral vein. The summed ¹³C MR spectra are also shown.