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NAD(P)H oxidase
NAD(P)H oxidase is a membrane-associated enzyme that catalyzes the production of superoxide– a reactive free radical– through a one electron transfer from NAD(P)H (NADH or NADPH) to oxygen as the electron acceptor. It is considered one of the major sources of superoxide anions in humans as well as bacteria, used in oxygen-dependent killing mechanisms for invading pathogens.
==Biological Function==
Superoxide produced from NADPH oxidase is used to kill bacteria and fungi by mechanisms that are not yet fully understood. Thus far, in E. coli it has been shown to undergo spontaneous dismutation in a pH and concentration-dependent reaction to yield hydrogen peroxide which together with superoxide anion damage a variety of biomolecules, most importantly damaging iron clusters.〔Djaman, O. (2004). Repair of Oxidized Iron-Sulfur Clusters in Escherichia coli. Journal of Biological Chemistry.〕 Release of iron can undergo Fenton reaction with hydrogen peroxide to yield hydroxyl radicals, which damage any biological molecule, including DNA.〔Cadet, J., Delatour, T., Douki, T., Gasparutto, D., Pouget, J., Ravanat, J., & Sauvaigo, S. (1999). Hydroxyl radicals and DNA base damage. Mutation Research-fundamental and Molecular Mechanisms of Mutagenesis.〕〔Slauch, J. (2011). How does the oxidative burst of macrophages kill bacteria? Still an open question. NCBI.〕 The enzymatic activity for producing this type of Reactive Oxygen Species (ROS) exceeds those of other oxidase enzymes including Xanathine oxidase and mitochondrial oxidase.〔Rajagopalan S, Kurz S, Mu ̈nzel T, Tarpey M, Freeman BA, Griendling KK, Harrison DG. Angiotensin II mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation: contribution to alterations of vasomotor tone. J Clin Invest. 1996;97:1916 –1923.〕〔Mohazzab-H KM, Kaminski PM, Wolin MS. Lactate and PO2 modulate superoxide anion production in bovine cardiac myocytes: potential role of NADH oxidase. Circulation. 1997;96:614–620.〕 In most studies, NADH is believed to be the preferred electron donor, although reports have shown that NAPDH is equally used as the electron donor.
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