NADPHoksidaasin

NADPHoksidaasin, commonly called NADPH oxidase, is a family of membrane-associated enzyme complexes that generate reactive oxygen species by transferring electrons from NADPH to molecular oxygen. The best-known member is the phagocyte NADPH oxidase, which produces superoxide radicals used in antimicrobial defense during the respiratory burst. The system is essential for innate immunity, helping phagocytes kill engulfed bacteria and fungi.

Structure and regulation: The core catalytic component is a membrane-bound heterodimer formed by gp91phox (also known as NOX2) and p22phox, together referred to as cytochrome b558. In resting cells, cytosolic regulatory subunits including p47phox, p67phox, and p40phox, along with the small GTPase Rac (Rac1 or Rac2), reside in the cytosol. Activation signals trigger phosphorylation and assembly of these subunits at the membrane, forming an active oxidase complex. Other tissues utilize NOX family enzymes (NOX1-5, DUOX1-2) that share the same electron transfer mechanism but use distinct regulatory subunits and tissue-specific functions.

Mechanism and products: The activated oxidase transfers electrons from NADPH in the cytosol through FAD and heme cofactors within the catalytic subunit to molecular oxygen, reducing O2 to superoxide (O2−). Superoxide can be dismutated to hydrogen peroxide and other reactive oxygen species, contributing to microbial killing and to redox signaling.

Physiological and clinical significance: In phagocytes, this system drives antimicrobial defense and inflammation. NOX enzymes in non-phagocytic cells participate in signaling pathways related to cell growth, differentiation, and response to stress. Genetic defects in NADPH oxidase components cause chronic granulomatous disease, characterized by recurrent infections. Aberrant activity is linked to inflammatory diseases, vascular pathology, neurodegeneration, and cancer; selective NOX inhibitors are under investigation for therapy.