Figure 4

MPA of the 100% 1-¹³C glucose ILE data suggests an active ED pathway. (a) Four different Metabolic Models (I-IV) were constructed to explain the ILE data; each column represents a different model. Pathways included in a model are denoted by a “Y”, color-coded according to the color of the pathway in Figure 3. (b) Vertical bars represent the SSR of each model and horizontal lines represent the acceptable SSR corresponding to the number of redundant isotopomer measurements in each model. Models II and IV, both containing the ED pathway show a significantly decreased SSR compared to otherwise identical models lacking the ED pathway. (c) The carbon rearrangements of the EMP and ED pathways are shown, with ¹³C atoms shown as blue squares and ¹²C atoms shown as white squares. The EMP pathway transfers ¹³C from glucose C-1 to pyruvate C-3, whereas the ED pathway transfers ¹³C from glucose C-1 to pyruvate C-1 (red boxes). (d) The isotopomers of pyruvate reflect those of the amino acid alanine. The measured abundances of alanine isotopomers are compared against the simulated enrichments of Models I and II. Model I that lacks the ED pathway over-simulates the abundance alanine{123}, and under-simulates the abundance of alanine{1 23}. These errors are corrected in Model II, which utilizes the ED pathway. Isotopomer notation is explained in text.