13C distribution in first turn of the Krebs cycle with [13C3]- or [lsqb]13C1-1]pyruvate.
A, [13C3]pyruvate enters the Krebs cycle either through pyruvate carboxylase (PC, blue circles) or pyruvate dehydrogenase (PDH, red circles). Colored circles indicate 13C label for selected metabolites. PDH-derived and PC-derived metabolites are represented in the inner and outer circle, respectively. PC notably produces M + 3 citrate, malate, and fumarate during the first turn of the Krebs cycle, whereas PDH notably produces M + 2 citrate. [13C2-2,3]Glu and [13C2-3,4]Glu isotopomers are associated with PC and PDH activity, respectively. B, labels from [13C-1]pyruvate (blue circle, derived from [13C2-3,4]glucose) enter the Krebs cycle exclusively through PC as the labeled carbon is lost in the PDH reaction. Other isotopomers are possible but not shown. IDH, isocitrate dehydrogenase; GDH, glutamate dehydrogenase; GS, glutamine synthetase; GLS, glutaminase; ME, malic enzyme; GOT, glutamic-oxaloacetic transaminase.