Figure 4.

Current ascorbate cycling model for NTBI reduction and uptake. Ascorbate provides the necessary reducing equivalents to reduce ferric iron to ferrous iron, by becoming oxidized to DHA. Fe²⁺ is then transported, putatively by DMT1, across the membrane. DHA is now cycled back to the intracellular phase via glucose transporters such as GLUT1. Internal regeneration of DHA to ascorbate occurs via direct two-electron reduction using glutathione/glutathione disulfide couple (GSH/GSSG). Reduction also occurs enzymatically using NADPH and GSH dependent enzymes. The regenerated ascorbate crosses the membrane via anion channels and the process repeats.