Figure 1.

Chemical pathways used for Glc metabolism modeling. The mathematical model considers metabolic steady-state conditions and is simplified in order to consider only the chemical pools with high concentration, such as NAA and Glyc, as well as the pools located at chemical branch points. The carbon chain, composed of 6 carbons, is split into 2 chains of three carbons at the level of F-1,6-bisP resulting in the production of 2 molecules of GA-3-P. Therefore, the total flux of molecules (in micromol/g/min) is doubled. Subsequently to a labeling procedure with [1-¹³C]-labeled Glc, only one carbon in the F-1,6-bisP molecule is labeled, and only one of the two produced GA-3-P is labeled. Therefore, a dilution of the labeling by a factor of 2 is observed after F-1,6-bisP. Thus, the labeling flux remains the same as the one entering the pool of F-1,6-bisP (i.e. V_Glc). Glc, Glyc, G-6-P, F-1,6-bisP, GA-3-P, Pyr, TCA, A CoA and NAA stand for glucose, glycogen, glucose-6-phosphate, fructose 1,6-bisphosphate, glyceraldehyde-3-phosphate, pyruvate, tricarboxylic acid cycle, Acetyl-CoA, and N-acetyl-aspartate, respectively. V_Glc represents the rate of Glc metabolism via glycolysis and V_Glyc the exchange rate with the Glyc molecule. V_PDH represents the flux of pyruvate into acetyl-CoA catalysed by pyruvate dehydrogenase (PDH), and V_PC the rest of the efflux from pyruvate to oxaloacetate thank to the pyruvate carboxylase (PC). The TCA cycle flux is represented by V_TCA.