The NADPH Oxidase of Leukocytes: The Respiratory Burst Oxidase

One of the most remarkable features of the host defense apparatus is its ability to deploy a large and complex group of highly reactive oxidizing agents for use in the destruction of invading pathogens. These reactive oxidants include a very large number of oxidized halogens and oxidizing radicals (Thomas et al. 1982; Liochev and Fridovich 1994), as well as singlet oxygen (Steinbeck et al. 1992). The starting material from which they all arise is superoxide (O 2 •− ; Fig. 1), which is generated under suitable conditions by certain cells of the immune system: professional phagocytes (neutrophils, eosinophils, and mononuclear phagocytes) and B lymphocytes (Babior et al. 1973; Volkman et al. 1984; Nathan 1987b; Maly et al. 1989; Sedgwick et al. 1990). The production of these reactive oxidants is associated with an abrupt but transient rise in oxygen consumption, so the metabolic event in which they are generated has come to be called the respiratory burst, and the O 2 •− -generating enzyme responsible for their production is known as the NADPH oxidase of leukocytes (also called respiratory burst oxidase ). The NADPH oxidase is a membrane-associated enzyme that catalyzes the one-electron reduction of oxygen to O 2 •− at the expense of NADPH (Babior et al. 1976; Dewald et al. 1979):2O2+NADPH→2O2⋅-+NADP++H+ The enzyme is dormant in resting cells, but comes to life when the cells are exposed to appropriate stimuli. Because the oxidants generated during the respiratory burst are so dangerous, the activity of the NADPH oxidase has to be tightly regulated in both time and space...