Role of Nicotinamide Quinone Oxidoreductase 1 (NQO1) in Protection against Toxicity of Electrophiles and Reactive Oxygen Intermediates

Abstract

This chapter elaborates the role of nicotinamide quinone oxidoreductase 1 (NQO1) in protection against toxicity of electrophiles and reactive oxygen intermediates. NQO1 is a broadly distributed FAD-dependent flavoprotein that catalyzes the reduction of a wide variety of quinones, quinone imines, nitroaromatics, and azo dyes. Its notable characteristics include: equal efficiency of NADH and NADPH as electron donors; an obligatory two-electron reduction mechanism without semiquinone intermediates; potent inhibition by dicumarol and similar anticoagulants which has been a valuable tool for assessing the functional role of this enzyme; and induction by a plethora of chemically diverse inducers that activate the regulatory antioxidant response element (ARE) of the NQO1 gene. The physiological functions of NQO1 are described in this chapter. Evidences are presented for the fact that NQO1 protects against electrophile toxicity, oxidative stress, and neoplasia. Regulation of NQO1 by antioxidant response elements (ARE) and consequences of disruption of the NQO1 Gene are discussed in the chapter. The chapter explores the epidemiological links of NQO1 polymorphism to the risk of developing cancer.