Xanthine dehydrogenase/aldehyde oxidase family
xanthine dehydrogenase/aldehyde oxidase family
AOX1 and XDH are classified as molybdo-flavoenzymes, since they require FAD besides Moco to oxidize their substrates. The primary structure of AOX1 and XDH is very similar and the catalytically active form of both types of enzymes is a homodimer consisting of two 150 kDa subunits. The monomeric subunit of both AOX1 and XDH is divided into three distinct regions: an amino-terminal 25-kDa domain containing two non-identical 2Fe/2S redox centers, a central 40-kDa domain where the FAD-binding site is located and a carboxy-terminal 85-kDa domain consisting of the Moco-binding site mapping close to the substrate pocket. XDH and AOX1 differ in their substrate specificity. XDH acts preferentially on the two purines, hypoxanthine and xanthine, oxidizing them to xanthine and uric acid, respectively. XDH is a key enzyme in the catabolism of purines. In contrast, the physiological role of human AOX1 is still a matter of debate but the substrate specificity is much broader and AOX1 is known to play an important role in the metabolism of drugs and other xenobiotics.