Production and purification of [U-13 C; U-2 H]G6P. Doubly labelled G6P was produced and purified using an ad hoc protocol developed in our laboratory and optimized for this work. [U-13 C, U-2 H]-G6P was enzymatically produced in a reaction medium containing 1.4 mg of Hexokinase from Saccharomyces cerevisiae (corresponding to 100 U), 2.6•10 -3 moles of [U-13 C, U-2 H]-Glucose , 3.4 • 10 -3 moles of ATP in 45 mL of a 100 mM Phosphate Buffer (pH = 7.25) and 6.9 • 10 -2 M of MgCl 2 solution. The reaction was monitored by 31 P and C NMR and completion attested after 25 h at ambient temperature. The reaction medium was then lyophilized, and the obtained solid was dissolved in the least possible H 2 O volume. This solution was then purified by size-exclusion chromatography (SEC) on a Sephadex® G25 resin. Fractions of 3 mL containing carbohydrates were collected and identified by a dehydration reaction with sulfuric acid (Figure SI-5 in the SI). Fractions #40 to #60 containing carbohydrates (brown spots) were lyophilized, weighted (Table -3), and the solids obtained were dissolved in 500 µL D 2 O. The amounts of G6P in these samples were measured by means of 13 C NMR. Peak assignment is presented in Fig. of the Supplementary Information. For quantification purposes, a capillary containing a 60 mM solution of 13 C-labelled glycine was placed inside an NMR tube filled with these 500 µL volumes of resuspended fractions. Quantification was performed using 13 C 1 (sum of both anomers) and C 6 resonance peaks. The 13 C 2 -13 C 5 region, was used for cross-checking (see Figure SI-8 in Supplementary Information).