NADPHoksidase

NADPH oxidase, also spelled NADPHoksidase in some languages, is a multi-subunit enzyme complex that transfers electrons from NADPH to molecular oxygen, generating reactive oxygen species such as superoxide. This respiratory burst is a key antimicrobial mechanism in professional phagocytes and also participates in signaling roles in various cell types.

The core of the enzyme is the membrane-bound cytochrome b558, formed by gp91phox (also called NOX2) and p22phox. In resting cells, cytosolic subunits p47phox, p67phox, and p40phox, together with the small GTPase Rac, reside in the cytosol. Upon activation, these subunits assemble with cytochrome b558 at the membrane, enabling electron transfer from NADPH in the cytosol to flavin adenine dinucleotide (FAD) and heme groups in gp91phox, and finally to oxygen in the extracellular or luminal space, producing superoxide. Superoxide can dismutate to hydrogen peroxide and further react to form other reactive species, which contribute to microbial killing in phagosomes and can participate in signaling pathways.

NOX family enzymes encompass several isoforms beyond NOX2, including NOX1-5 and the dual oxidases DUOX1-2, with tissue-specific expression and functions. NOX enzymes in nonphagocytic cells largely regulate signaling processes such as cell growth, differentiation, and vascular tone; DUOX enzymes have established roles in mucosal defense and thyroid hormone synthesis.

Clinical relevance includes chronic granulomatous disease (CGD), caused by defects in components of the NADPH oxidase complex, leading to impaired microbial killing and recurrent infections. Researchers study NADPH oxidases as targets for controlling oxidative stress in inflammatory diseases and cancer, and as models for plant defense enzymes known as respiratory burst oxidase homologs (RBOHs).