FIG. 3.

Electron flow from NADPH to substrates via the Trx and GSH/Grx systems. NADPH as the main electron source reduces the selenoprotein thioredoxin reductase (TrxR), which delivers electrons to Trx, which then reduces protein (P) disulfides. NADPH also donates electrons to glutathione reductase (GR), which reduces glutathione disulfide (GSSG), thereby generating two molecules of reduced GSH. Electrons can then be delivered to oxidized Grx, which either possesses an active site disulfide bridge due to reduction of protein disulfides or a glutathionylated N-terminal active site Cys from reducing a GSH-mixed disulfide.