It is well established that phase I metabolism of clinically useful drugs is generally carried out by the family of cytochrome P450 mono-oxygenases (CYP450). These enzymes reside in the endoplasmic reticulum of the hepatocyte and oxidize various types of chemical functionalities with particular reference to aromatic rings, which are often the main structural components of different drugs. In spite of this, there is growing evidence for the involvement of a distinct enzyme, i.e. human aldehyde oxidase 1 (AOX1), in phase I metabolism (Garattini and Terao, 2011, 2012, 2013; Pryde et al., 2010). Human AOX1 (EC is a cytosolic enzyme belonging to the family of molybdo-flavoproteins along with other mammalian AOX isoenzymes and the structurally related xanthine oxidoreductase (XOR) protein. AOXs and XOR are distributed throughout the animal kingdom and have been characterized in eukaryotic and prokaryotic organisms (Garattini et al., 2003; Hesberg et al., 2004; Mendel, 2007; Pritsos, 2000; Zhang and Gladyshev, 2008). While a single XOR form is known, up to four different AOXs have been described in insects (Marelja et al., 2014), plants (Kurosaki et al., 2013), and vertebrates (AOX1, AOX2; AOX3; AOX4) (Garattini et al., 2003, 2008; Kurosaki et al., 2013). 84Mammalian XOR is the key enzyme in the catabolism of purines, catalyzing the oxidation of hypoxanthine into xanthine as well as xanthine into uric acid, whereas the physiological function of mammalian AOXs is still largely obscure.