Model of NADPH oxidase activation.

In unstimulated neutrophils, the subunits of the NADPH oxidase are separated in the cytoplasmic and membrane compartments. The plasma and specific granule membranes contain flavocytochrome b with its p22^phox and glycosylated gp91^phox subunits and the small GTPase Rap1a. The flavin and heme groups (Fe) that mediate the transfer of electrons from NADPH to molecular oxygen appear to be localized in the gp91^phox subunit. The cytosolic components p47^phox and p67^phox may exist as a preformed complex of 260 kDa, which also includes at least one additional protein, p40^phox. The small GTPase Rac is also present in the cytosol in its inactive GDP bound state, in a complex with a GDP dissociation inhibitor (Rho-GDI). With neutrophil activation, the cytosolic phox subunits translocate to the membrane, which is dependent upon phosphorylation of p47^phox and exposure of an SH3 domain that binds to p22^phox. Other binding sites between p47^phox and gp91^phox are also likely to be important. Neutrophil activation also triggers the conversion of Rac-GDP to Rac-GTP and dissociation from Rho-GDI. Rac-GTP is membrane-associated, interacting with p67^phox and another undetermined site in the oxidase complex.