Simulations of 6PGDH inhibition and 6-PG accumulation.

(A–B) The effects of inhibition of 6PGDH on 6-PG concentrations and metabolic fluxes were simulated by reducing V_max,6PGDH in model C and D at high oxidative stress (k_TOX = 200 µl·min⁻¹·mg protein⁻¹). Simulations at low oxidative stress (k_TOX = 2 µl·min⁻¹·mg protein⁻¹) are shown in Figure S6. ATP production flux as steady-state flux through PFK is indicated in red, while trypanothione reductase steady-state flux is indicated in yellow, both plotted on the left y-axis. Steady-state concentration of cytosolic (blue) and glycosomal (green) 6-phosphogluconate are plotted on the right y-axis. Shaded areas indicate interquartile ranges. (C) Steady-state flux through glycolysis as a function of the glycosomal 6-PG concentration in model A. A glycosomal 6-PG concentration of around 500 mM reduces the glycolytic flux by 50%.