Figure 7
Relative steady state concentrations of all metabolites in the RPE and the rods as [GLUT1] decreases from 1 to 0, with all metabolites scaled to 100 at GLUT1 = 1 (representing the healthy case). Left panel: Metabolite concentrations in the RPE. The glucose concentration in the RPE (gray curve) stays close to its healthy value up until [GLUT1] has decreased by approximately 80% , i.e., [GLUT] = 0.2, likely due to the regulating mechanisms that block the glucose passage to the rods. There is a slight increase in the G6P and significant increase in the F16BP. Initially, the pyruvate concentration decreases at an almost constant rate because it highly depends on the rods’ contribution of lactate, which is lower with every step. However, when [GLUT1] decreases from approximately 0.45 down to 0.2, the rate at which pyruvate decreases and the rate at which F16BP increases both slow down. As [GLUT1] becomes even scarcer ([GLUT1] less than approximately 0.2), the glucose concentration decays rapidly. Right panel: Metabolite concentrations in the rods. The RPE’s regulating mechanisms block the passage of glucose to the rods, making its concentration decrease with every step. As [GLUT1] decreases, the production of aerobic glycolysis intermediate products is favored (slowest overall decrease). Among these are the production of G3P by the KP (essential for the rods’ OS renewal) and the production of lactate (that contributes to the RPE’s survival); the others are G6P and F16BP. Meanwhile, the production of NADPH (by the PPP, and the metabolite that undergoes the most rapid decrease) and pyruvate (that fuels the rods’ OXPHO) are the most affected by the response of the regulating mechanisms to the [GLUT1] decrease and the consequential glucose shortage. When [GLUT1] is less than approximately 0.2, the glucose directed to the rods is too small to maintain any of its functions, and all the metabolites concentrations rapidly go to zero.
