ABSTRACT

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 but not for p47, suggesting that p67 and p47 have individual roles in controlling electron flow from NADPH to oxygen. Here, we provide direct evidence that p67 alone can facilitate electron flow from NADPH to the flavin center of NADPH oxidase in the absence of p47, resulting in the reduction of enzyme FAD, whereas the presence of p47 is required in order for electron transfer to proceed beyond the flavin center to the heme in cytochrome b and thence to oxygen.

FOOTNOTES

*

This work was supported by National Institutes of Health Grant AI24838 and General Clinical Research Center Grant RR00833 (to J. T. C.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked ``advertisement'' in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§

To whom correspondence should be addressed: Dept. of Molecular & Experimental Medicine, CAL-1, The Scripps Research Institute, 10666 North Torrey Pines Rd., La Jolla, CA 92037. Tel.: 619-554-3654; Fax: 619-554-6988.

¶

Present address: Immunology Dept., Genentech Inc., South San Francisco, CA 94080.

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The abbreviations used are: O, superoxide anion radical; CGD, chronic granulomatous disease; OG, octyl--D-glucopyranoside.

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J. Rae and J. T. Curnutte, unpublished data.

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J. Rae and J. T. Curnutte, manuscript in preparation.

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A. R. Cross, P. G. Heyworth, J. Rae, and J. T, Curnutte, manuscript in preparation.

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