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 key 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. May be a prominent source of superoxide generation via the one-electron reduction of molecular oxygen. May also catalyze nitric oxide (NO) production via the reduction of nitrite to NO with NADH or aldehyde as electron donor. 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. Is very potently inhibited by raloxifene (PubMed:26842593). Also inhibited by estradiol, ethinyl estradiol, hydralazine, menadione, isovanillin and thioridazine. Not inhibited by allopurinol, a xanthine dehydrogenase potent inhibitor (PubMed:22031625, PubMed:22522748, PubMed:22996261, PubMed:9224775, PubMed:26322824). kcat is 6.4 min(-1) for benzaldehyde oxidation, 5.6 min(-1) for phthalazine oxidation, 12.2 min(-1) for phenanthridine oxidation and 5.6 min(-1) for chloroquinazolinone oxidation. Homodimer. Abundant in liver, expressed in adipose tissue and at lower levels in lung, skeletal muscle, pancreas. In contrast to mice, no significant gender difference in AOX1 expression level (at protein level). Not detected in preadipocytes but strongly induced in mature adipocytes. In liver, is down-regulated by adiponectin and by the PPARA agonist, fenofibric acid. 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:22335465). Belongs to the xanthine dehydrogenase family. Was originally thought to be a xanthine dehydrogenase.