NRH : quinone oxidoreductase2 (NQO2)

The quinone oxidoreductases [NAD(P)H:quinone oxidoreductase1 (NQO1) and NRH :quinone oxidoreductase2 (NQO2)] are flavoproteins. NQO1 is known to cataly se metabolic detoxification of quinones and protect cells from redox cyclin g, oxidative stress and neoplasia. NQO2 is a 231 amino acid protein (25 956 mw) that is 43 amino acids shorter than NQO1 at its carboxy-terminus. The human NQO2 cDNA and protein are 54 and 49% similar. to the human liver cyto solic NQO1 cDNA and protein. Recent studies have revealed that NQO2 differs from NQO1 in its cofactor requirement. NQO2 uses dihydronicotinamide ribos ide (NRH) rather than NAD(P)H as an electron donor. Another difference betw een NQO1 and NQO2 is that NQO2 is resistant to typical inhibitors of NQO1, such as dicoumarol, Cibacron blue and phenindone. Flavones, including querc etin and benzo(a)pyrene, are known inhibitors of NQO2. Even though overlapp ing substrate specificities have been observed for NQO1 and NQO2, significa nt differences exist in relative affinities for the various substrates. Ana lysis of the crystal structure of NQO2 revealed that NQO2 contains a specif ic metal binding site, which is not present in NQO1. The human NQO2 gene ha s been precisely localized to chromosome 6p25. The human NQO2 gene locus is highly polymorphic, The NQO2 gene is ubiquitously expressed and induced in response to TCDD. Nucleotide sequence analysis of the NQO2 gene promoter r evealed the presence of several cis-elements, including SP1 binding sites, CCAAT box, xenobiotic response element (XRE) and an antioxidant response el ement (ARE). The complement of these elements regulates tissue specific exp ression and induction of the NQO2 gene in response to xenobiotics and antio xidants. The in vivo role of NQO2 and its role in quinone detoxification re mains unknown, (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.