Structure and mechanism of cytosolic quinone reductases.

نویسندگان

  • M A Bianchet
  • C Foster
  • M Faig
  • P Talalay
  • L M Amzel
چکیده

Introduction Quinones are ubiquitous dietary compounds. Reduction of quinones by one-electron reduction systems (cytochrome P450 reductases) results in the formation of reactive semiquinones that can be re-oxidized to quinones by molecular oxygen with the formation of superoxide radical (02-*). Superoxide can lead to the formation of other reactive oxygen species, including the highly mutagenic and carcinogenic hydroxyl radical. In addition, the presence of quinones and their one-electron reduction products can result in the depletion of reduced thiol species. Cytosolic quinone reductase (QR) 1 provides a pathway that obviates all these deleterious reactions. Reduction of quinones via the obligatory two-electron reduction carried out by QR results in the formation of hydroquinones that can be glucuronidated and readily excreted. QR1 [NAD(P)H : (quinone acceptor) oxidoreductase; EC 1.6.99.21 is a widely distributed, predominantly cytosolic, FAD-containing flavoprotein that promotes the obligatory two-electron reduction of many quinones and quinoneimines. (The enzyme has also been referred to as menadione reductase, DT-diaphorase and vitamin-K reductase). It uses NADH or NADPH as reductants with equal facility and is potently inhibited by dicoumarol and similar anticoagulants. Furthermore, QR activity is elevated in many animal tissues and cell lines by addition of xenobiotics. The discovery, purification, molecular characteristics, induction and other properties of this enzyme have been presented previously [ 1,2]. The purification and properties of another mammalian cytosolic FAD-dependent flavoprotein was described in the early 1960's by Liao et al. [3]. This enzyme was able to catalyse the oxidation of reduced N-ribosyland N-alkylnicotinamides by menadione and other quinones. Recently, the determination of the sequence indicated that this enzyme is highly homologous with QR1 [4,5], leading to the conclusion that it is

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عنوان ژورنال:
  • Biochemical Society transactions

دوره 27 4  شماره 

صفحات  -

تاریخ انتشار 1999