title: Flavin-containing reductase: new perspective on the detoxification of nitrobenzodiazepine.
abstract: BACKGROUND
  Nitrobenzodiazepines (NBDZs) are important hypnotic-sedative drugs prescribed in clinic for treating sleeping disorders. The long-lasting efficacy of NBDZs has made them to be used purposely resulting in neurophysiological impairment and internal toxicity. While many studies have investigated the biotransformation of NBDZs, studies seldom are found on their reductive metabolism or the enzymes that act on these drugs.
  
  
  METHODS
  In this review, we describe the finding of human hepatic NADPH-cytochrome P450 reductase (EC 1.6.2.4) and Escherichia coli nitroreductase NfsB (EC 1.5.1.34) in the reductive conversion of NBDZ to a harmless metabolite 7-aminobenzodiazepine and present the facts of reductive activity in other flavin-containing reductases. A historic investigation on the reduction of nitroaromatics and quinones by the selected flavoenzymes is performed. In addition, flavin domain structures of these enzymes are discussed.
  
  
  RESULTS
  The reader will gain a comprehensive understanding of the reductive metabolism of NBDZs including the structure-activity relationship of the selected flavoproteins.
  
  
  CONCLUSIONS
  The discovery of novel flavin-containing reductase on NBDZ in the body is essential for the development of more active nitroreductases which may find applications in the detoxification of NBDZ.
authors.affiliation: Institute of Biological Chemistry, Nankang, Taipei, Taiwan.
authors.forename: Shiuan-Woei
authors.initials: SW
authors.lastname: LinWu
authors.forename: Andrew H-J
authors.initials: AH
authors.lastname: Wang
authors.forename: Fu-Chuo
authors.initials: FC
authors.lastname: Peng
mesh_terms: D000818:Animals; D001569:Benzodiazepines / Q000009:adverse effects / Q000378:metabolism* / Q000633:toxicity; D004926:Escherichia coli / Q000201:enzymology; D029968:Escherichia coli Proteins / Q000378:metabolism*; D005420:Flavoproteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism*; D009601:Nitroreductases / Q000378:metabolism*; D011809:Quinones / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D029968:Escherichia coli Proteins; D005420:Flavoproteins; D006993:Hypnotics and Sedatives; D011809:Quinones; D001569:Benzodiazepines; D009251:NADPH-Ferrihemoprotein Reductase; C116054:NfsB protein, E coli; D009601:Nitroreductases