FIG. 5.

Redox sensing and metabolic reprioritization by GAPDH. GAPDH, a critical enzyme on the energy generating triosephosphate pathway, has a highly reactive Cys-thiolate ion in the active site (S⁻). In normal conditions, GAPDH is active and flux of glucose through the triose-P pathway for energetics versus through the pentose-P pathway for generating NADPH is balanced. During oxidative stress, H₂O₂ oxidizes the active site thiolate, which inactivates glycolytic activity of GAPDH, lowering glycolytic flux and making more glucose available for the pentose-P pathway; and converts GAPDH into a nuclear-localized transcription factor that further favors antioxidant activities of NADPH arising from the pentose-P pathway. GAPDH, glyceraldehyde-3-phosphate dehydrogenase.