Oxidase with broad substrate specificity, oxidizing aromatic azaheterocycles, such as N1-methylnicotinamide, N-methylphthalazinium and phthalazine, as well as aldehydes, such as benzaldehyde, retinal, pyridoxal, and vanillin. Plays a role in the metabolism of xenobiotics and drugs containing aromatic azaheterocyclic substituents. Participates in the bioactivation of prodrugs such as famciclovir, catalyzing the oxidation step from 6-deoxypenciclovir to penciclovir, which is a potent antiviral agent. Is probably involved in the regulation of reactive oxygen species homeostasis. Is a prominent source of superoxide generation via the one-electron reduction of molecular oxygen. Also catalyzes nitric oxide (NO) production; under anaerobic conditions, reduces nitrite to NO with NADH or aldehyde as electron donor, but under aerobic conditions, NADH is the preferred substrate. These reactions may be catalyzed by several isozymes. May play a role in adipogenesis. an aldehyde + H2O + O2 = a carboxylate + H(+) + H2O2 H2O + O2 + retinal = H(+) + H2O2 + retinoate Binds 2 [2Fe-2S] clusters per subunit. Binds 1 FAD per subunit. Binds 1 Mo-molybdopterin (Mo-MPT) cofactor per subunit. Inhibited by menadione and isovanillin. Not inhibited by allopurinol, a xanthine dehydrogenase potent inhibitor. Inhibited by the flavonoids quercetin, myricetin and genistein. Nitric oxide generation is inhibited by raloxifene and competitively inhibited by an increase in oxygen levels. Optimum pH is 6.0 for nitrite oxide generation. Activity decreases below pH 5.0 and above pH 8.0 (PubMed:19801639). Homodimer. Expression in liver (at protein level). Also detected in heart, lung, spleen and kidney. The N-terminus is blocked. The sequence variants between males and females could be due to differences between individual animals, reflect gender differences or arise from technical problems (PubMed:9920943). The sequence shown here is that of a Sprague-Dawley female. Male and female rats possess kinetically distinct forms which may be due to differences in redox states. AOX genes evolved from a xanthine oxidoreductase ancestral precursor via a series of gene duplication and suppression/deletion events. Different animal species contain a different complement of AOX genes encoding an equivalent number of AOX isoenzymes. In mammals, the two extremes are represented by certain rodents such as mice and rats, which are endowed with 4 AOX genes, and by humans, whose genome is characterized by a single active gene (PubMed:23263164). Belongs to the xanthine dehydrogenase family. The experimental design does not allow to distinguish AOX1 from AOX3 in rat liver as the effector of the superoxide and nitric oxide production (PubMed:17353002 and PubMed:19801639).