The role of G6PD in protecting red blood cells from oxidative damage. (A) In G6PD-normal red blood cells, G6PD and 6-phosphogluconate dehydrogenase—2 of the enzymes of the PPP—provide an ample supply of NADPH, which in turn regenerates GSH when this is oxidized by ROS (eg, superoxide, O₂⁻ and H₂O₂). Thus, when O₂⁻ (meant here to represent itself and other ROS) is produced by pro-oxidant compounds such as primaquine, or the glucosides in fava beans (divicine), or the oxidative burst of neutrophils, these ROS are rapidly neutralized; similarly, when rasburicase administered to degrade uric acid produces an equimolar amount of H₂O₂, this is rapidly degraded by the combined action of GSH peroxidase, catalase, and Prx2 (peroxiredoxin-2: all 3 mechanisms are NADPH dependent). (B) In G6PD-deficient red blood cells, where the enzyme activity is reduced, NADPH production is limited, and it may not be sufficient to cope with the excess ROS generated by pro-oxidant compounds and the consequent excess H₂O_2. This diagram also explains why a defect in GSH reductase has very similar consequences to G6PD deficiency. Modified from Luzzatto, Nannelli, and Notaro.⁵³  PPP, pentose phosphate pathway.