Figure 6

Expected ¹³C labeling patterns in mitochondrial Krebs cycle intermediates and byproducts with [U-¹³C]-Glc as tracer. The cycle reactions are depicted without (panel A) or with (panel B) anaplerotic pyruvate carboxylase (PC) reaction and the ¹³C positional isotopomer patterns illustrated are the result of one cycle turn. In the absence of pyruvate carboxylation, Glu is labeled at C4 and C5 positions via the forward cycle reactions while Glu is labeled at C2 and C3 when pyruvate carboxylation is active (panels A and B). The possibility that a separate pool of pyruvate derived from Ala for entry into the Krebs cycle via pyruvate carboxylation is depicted in panel B, along with the contribution of the non-oxidative branch of the pentose phosphate pathway (PPP) to the pyruvate pool. Isotopic scrambling occurs at the symmetric succinate, leading to the redistribution of ¹³C labels into its four carbons, two each at a time (blue and green carbons). Red or blue and green letter C's represent ¹³C labeled carbons before or after scrambling, respectively; blue pyruvate denotes a separate pool of pyruvate; solid and dashed arrows denote favorable single and multi-step reactions, respectively; open arrows in panel A delineate ¹³C-labeled OAA after one turn from unlabeled pre-existing OAA.