NADPH oxidase

The NADPH oxidase (nicotinamide adenine dinucleotide phosphate-oxidase) is a membrane-bound enzyme complex that faces the extracellular space. It can be found in the plasma membrane as well as in the membranes of phagosomes used by neutrophil white blood cells to engulf microorganisms. Isoforms are designated NOX1, NOX2, NOX3, and NOX4.

It is made up of six subunits. These subunits are:

Under normal circumstances, the complex is latent in neutrophils and is activated to assemble in the membranes during respiratory burst.

NADPH oxidase generates superoxide by transferring electrons from NADPH inside the cell across the membrane and coupling these to molecular oxygen to produce superoxide anion, a reactive free-radical. Superoxide can be produced in phagosomes, which contain ingested bacteria and fungi, or it can be produced outside of the cell. In a phagosome, superoxide can spontaneously form hydrogen peroxide that will undergo further reactions to generate reactive oxygen species (ROS).

Superoxide kills bacteria and fungi by mechanisms that are not yet fully understood (see article on superoxide), but may inactivate critical metabolic enzymes, initiate lipid peroxidation, and liberate redox-active iron, which allows the generation of indiscriminate oxidants such as the hydroxyl radical. It is presumed that superoxide kills bacteria directly, as the virulence of many pathogens is dramatically attenuated when their superoxide dismutase (SOD) genes are deleted. However, downstream products of superoxide also include hydrogen peroxide and hypochlorous acid, the reactive agent in bleach.

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