THE CYTOSOLIC ACTIVATING FACTORS P47(PHAX) AND P67(PHAX) HAVE DISTINCT ROLES IN THE REGULATION OF ELECTRON FLOW IN NADPH OXIDASE

We have previously shown that the human neutrophil superoxide-generating NADPH oxidase possesses a novel dye reductase activity (Cross, A. R., Yarchover, J. L., and Curnutte, J. T. (1994) J. Biol. Chem. 269, 21448-21454). This activity exhibited an absolute requirement for the cytosolic activating factor p67(phox) but not far p47(phox), suggesting that p67(phox) and p47(phox) have individual roles in controlling electron flow from NADPH to oxygen. Here, we provide direct evidence that p67(phox) alone can facilitate electron flow from NADPH to the flavin center of NADPH oxidase in the absence of p47(phox), resulting in the reduction of enzyme FAD, whereas the presence of p47(phox) is required in order for electron transfer to proceed beyond the flavin center to the heme in cytochrome b(-245) and thence to oxygen.