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Gene Review

AOX1  -  aldehyde oxidase 1

Homo sapiens

Synonyms: AO, AOH1, Aldehyde oxidase, Aldehyde oxidase 1, Azaheterocycle hydroxylase
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Disease relevance of AOX1


Psychiatry related information on AOX1


High impact information on AOX1

  • Anaerobic reduction kinetics of the zucchini squash ascorbate oxidase (AO; L-ascorbate:oxygen oxidoreductase, EC by pulse radiolytically produced CO2- radical ions were investigated [6].
  • On the basis of these results, it was apparent that the success of 6- deoxyacyclovir as a prodrug in vivo would depend upon how well its desired activation by xanthine oxidase competed with the nonactivating oxidations by aldehyde oxidase [7].
  • 6- Deoxyacyclovir and the major products of its oxidation by aldehyde oxidase lacked appreciable activity against herpes simplex type I in vitro [7].
  • It was also oxidized by aldehyde oxidase (EC largely to 8-hydroxy-6- deoxyacyclovir [2-amino-8-hydroxy-9-[(2-hydroxyethoxy)methyl]-9H-purine] and then to 8- hydroxyacyclovir [2-amino-6,8-dihydroxy-9[(2-hydroxyethoxy)methyl]-9H-purine] [7].
  • The apoplastic enzyme ascorbate oxidase (AO) also regulates the reduction/oxidation (redox) state of the apoplastic ascorbate pool [8].

Chemical compound and disease context of AOX1

  • The molybdenum iron-sulphur protein from Desulfovibrio gigas as a form of aldehyde oxidase [9].
  • The intramolecular electron transfer (ET) between the type 1 Cu(I) and the type 2 Cu(II) sites of Alcaligenes xylosoxidans dissimilatory nitrite reductase (AxNiR) has been studied in order to compare it with the analogous process taking place in ascorbate oxidase (AO) [10].
  • Pargyline protected human lymphoma U937 cells against UVB-induced apoptosis, by reducing AO activity, mitochondrial uncoupling and cytochrome c release [11].
  • In order to establish an efficient process to decompose environmentally toxic aldehydes, dioxygen-dependent aldehyde oxidase (ALOD) from microorganisms was first sought, and some bacteria and actinomycetes were found to produce the enzyme in their cells [12].

Biological context of AOX1

  • A sequence homologous to AOX2-UAS was also found in the AOX1 promoter, and in methanol-regulated promoters in other methylotrophic yeast [13].
  • The C. neoformans alternative oxidase gene (AOX1) was found to exist as a single copy in the genome, and it encodes a putative protein of 401 amino acids [14].
  • Different expression plasmids were constructed in which the cDNAs of the two receptors were cloned under the transcriptional control of the highly inducible promoter of the P. pastoris alcohol oxidase 1 (AOX1) gene [15].
  • Strains using either the AOX1 or the GAP promoter were compared at different gene copy numbers [16].
  • P. pastoris with a MutS phenotype was selected to express A33scFv, which was cloned under regulation of the methanol-inducible AOX1 promoter [17].

Anatomical context of AOX1

  • The AO gene is highly expressed in glial cells of human spinal cord [1].
  • The aox1 mutant strain was significantly less virulent than both the wild type and the reconstituted strain in the murine inhalational model, and it also had significantly impaired growth within a macrophage-like cell line [14].
  • Incubation of O6-benzylguanine with human liver cytosol resulted in the formation of O6-benzyl-8-oxoguanine, which was inhibited by menadione, a potent inhibitor of aldehyde oxidase [18].
  • Respiratory rates involving the alternative oxidase (AO) were studied in mitochondria from Tapesia acuformis [19].
  • An oxidized product formed by cytosolic aldehyde oxidase was the predominant species both in urine and human hepatocytes in vitro [20].

Associations of AOX1 with chemical compounds


Regulatory relationships of AOX1


Other interactions of AOX1

  • Two 2039 bp koala liver AOX cDNAs, designated AOX1 and AOX2, were cloned by reverse transcription-polymerase chain reaction and rapid amplification of cDNA ends [26].
  • The human molybdenum cofactor sulfurase (HMCS) gene, the human ma-l homologue, is therefore a candidate gene responsible for classical xanthinuria type II, which involves both XDH and AO deficiencies [27].
  • The human endothelin B receptor (ET(B) receptor) was produced in the methylotrophic yeast Pichia pastoris under transcriptional control of the highly inducible alcohol oxidase 1 (AOX1) gene promoter [28].
  • Xanthine dehydrogenase and aldehyde oxidase, but not sulfite oxidase and nitrate reductase, require the post-translational sulfuration of their Mo-site for becoming active [29].
  • However, one would expect interindividual variation in the extent of oxidation of O6-benzylguanine depending on the levels of aldehyde oxidase, CYP1A2, and CYP3A4 [18].

Analytical, diagnostic and therapeutic context of AOX1

  • GeneChip experiments indicated that recombinant adiponectin downregulates aldehyde oxidase 1 (AOX1) expression and this was confirmed by real-time RT-PCR and immunoblot [2].
  • METHODS: Amplifying hVEGF165 cDNA by PCR, after confirmed by DNA sequence analysis, the gene was inserted into the Pichia pastoris expression vector pPIC9K containing AOX1 promoter and a secreting signal peptides, the recombinant expression plasmid pPIC9K/VEGF165 was constructed and transformed into KM71 [30].
  • Significant correlations were found between AO activity and various growth indices (age, body weight, body surface area, and liver volume) [31].
  • This work focuses on the elucidation of the electron-transfer mechanism of the monoenzymatic unmediated AO-modified biosensor [32].
  • Southern blot analysis conducted on genomic DNA from various animal species with specific cDNA probes indicates that the AO gene is less conserved than the XOR gene during evolution [33].


  1. Analysis of aldehyde oxidase and xanthine dehydrogenase/oxidase as possible candidate genes for autosomal recessive familial amyotrophic lateral sclerosis. Berger, R., Mezey, E., Clancy, K.P., Harta, G., Wright, R.M., Repine, J.E., Brown, R.H., Brownstein, M., Patterson, D. Somat. Cell Mol. Genet. (1995) [Pubmed]
  2. Aldehyde oxidase 1 is highly abundant in hepatic steatosis and is downregulated by adiponectin and fenofibric acid in hepatocytes in vitro. Neumeier, M., Weigert, J., Sch??ffler, A., Weiss, T.S., Schmidl, C., B??ttner, R., Bollheimer, C., Aslanidis, C., Sch??lmerich, J., Buechler, C. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  3. High-level production in Pichia pastoris of an anti-p185HER-2 single-chain antibody fragment using an alternative secretion expression vector. Gurkan, C., Symeonides, S.N., Ellar, D.J. Biotechnol. Appl. Biochem. (2004) [Pubmed]
  4. Production of human tissue factor using the Pichia pastoris expression system. Austin, A.J., Jones, C.E., Heeke, G.V. Protein Expr. Purif. (1998) [Pubmed]
  5. Differences in aldehyde oxidase activity in cytosolic preparations of human and monkey liver. Sugihara, K., Kitamura, S., Tatsumi, K., Asahara, T., Dohi, K. Biochem. Mol. Biol. Int. (1997) [Pubmed]
  6. Low activation barriers characterize intramolecular electron transfer in ascorbate oxidase. Farver, O., Pecht, I. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  7. 6-Deoxyacyclovir: a xanthine oxidase-activated prodrug of acyclovir. Krenitsky, T.A., Hall, W.W., de Miranda, P., Beauchamp, L.M., Schaeffer, H.J., Whiteman, P.D. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  8. Apoplastic ascorbate metabolism and its role in the regulation of cell signalling. Pignocchi, C., Foyer, C.H. Curr. Opin. Plant Biol. (2003) [Pubmed]
  9. The molybdenum iron-sulphur protein from Desulfovibrio gigas as a form of aldehyde oxidase. Turner, N., Barata, B., Bray, R.C., Deistung, J., Le Gall, J., Moura, J.J. Biochem. J. (1987) [Pubmed]
  10. The intramolecular electron transfer between copper sites of nitrite reductase: a comparison with ascorbate oxidase. Farver, O., Eady, R.R., Abraham, Z.H., Pecht, I. FEBS Lett. (1998) [Pubmed]
  11. Oxidation products of polyamines induce mitochondrial uncoupling and cytochrome c release. Maccarrone, M., Bari, M., Battista, N., Di Rienzo, M., Falciglia, K., Finazzi Agrò, A. FEBS Lett. (2001) [Pubmed]
  12. Production of aldehyde oxidases by microorganisms and their enzymatic properties. Yasuhara, A., Akiba-Goto, M., Fujishiro, K., Uchida, H., Uwajima, T., Aisaka, K. J. Biosci. Bioeng. (2002) [Pubmed]
  13. The positive and negative cis-acting elements for methanol regulation in the Pichia pastoris AOX2 gene. Ohi, H., Miura, M., Hiramatsu, R., Ohmura, T. Mol. Gen. Genet. (1994) [Pubmed]
  14. Role of alternative oxidase gene in pathogenesis of Cryptococcus neoformans. Akhter, S., McDade, H.C., Gorlach, J.M., Heinrich, G., Cox, G.M., Perfect, J.R. Infect. Immun. (2003) [Pubmed]
  15. Comparative biochemical and pharmacological characterization of the mouse 5HT5A 5-hydroxytryptamine receptor and the human beta2-adrenergic receptor produced in the methylotrophic yeast Pichia pastoris. Weiss, H.M., Haase, W., Michel, H., Reiländer, H. Biochem. J. (1998) [Pubmed]
  16. Effects of gene dosage, promoters, and substrates on unfolded protein stress of recombinant Pichia pastoris. Hohenblum, H., Gasser, B., Maurer, M., Borth, N., Mattanovich, D. Biotechnol. Bioeng. (2004) [Pubmed]
  17. An optimized fermentation process for high-level production of a single-chain Fv antibody fragment in Pichia pastoris. Damasceno, L.M., Pla, I., Chang, H.J., Cohen, L., Ritter, G., Old, L.J., Batt, C.A. Protein Expr. Purif. (2004) [Pubmed]
  18. Human liver oxidative metabolism of O6-benzylguanine. Roy, S.K., Korzekwa, K.R., Gonzalez, F.J., Moschel, R.C., Dolan, M.E. Biochem. Pharmacol. (1995) [Pubmed]
  19. New sequence data enable modelling of the fungal alternative oxidase and explain an absence of regulation by pyruvate. Joseph-Horne, T., Babij, J., Wood, P.M., Hollomon, D., Sessions, R.B. FEBS Lett. (2000) [Pubmed]
  20. Metabolic profile of XK469 (2(R)-[4-(7-chloro-2-quinoxalinyl)oxyphenoxy]-propionic acid; NSC698215) in patients and in vitro: low potential for active or toxic metabolites or for drug-drug interactions. Anderson, L.W., Collins, J.M., Klecker, R.W., Katki, A.G., Parchment, R.E., Boinpally, R.R., LoRusso, P.M., Ivy, S.P. Cancer Chemother. Pharmacol. (2005) [Pubmed]
  21. Comparison of levels of aldehyde oxidase with cytochrome P450 activities in human liver in vitro. Rodrigues, A.D. Biochem. Pharmacol. (1994) [Pubmed]
  22. Genetic studies of a cluster of acute lymphoblastic leukemia cases in Churchill County, Nevada. Steinberg, K.K., Relling, M.V., Gallagher, M.L., Greene, C.N., Rubin, C.S., French, D., Holmes, A.K., Carroll, W.L., Koontz, D.A., Sampson, E.J., Satten, G.A. Environ. Health Perspect. (2007) [Pubmed]
  23. Genome-wide expression profiling of the response to azole, polyene, echinocandin, and pyrimidine antifungal agents in Candida albicans. Liu, T.T., Lee, R.E., Barker, K.S., Lee, R.E., Wei, L., Homayouni, R., Rogers, P.D. Antimicrob. Agents Chemother. (2005) [Pubmed]
  24. Expression and characterization of a synthetic protein C activator in Pichia pastoris. Kunes, Y.Z., Sanz, M.C., Tumanova, I., Birr, C.A., Shi, P.Q., Bruguera, P., Ruiz, J.A., Sánchez-Martínez, D. Protein Expr. Purif. (2002) [Pubmed]
  25. Expression of a novel regenerating gene product, Reg IV, by high density fermentation in Pichia pastoris: production, purification, and characterization. Li, A., Crimmins, D.L., Luo, Q., Hartupee, J., Landt, Y., Ladenson, J.H., Wilson, D., Anant, S., Dieckgraefe, B.K. Protein Expr. Purif. (2003) [Pubmed]
  26. Identification and cloning of two forms of liver peroxisomal fatty Acyl CoA Oxidase from the koala (Phascolarctos cinereus). Ngo, S.N., McKinnon, R.A., Stupans, I. Gene (2003) [Pubmed]
  27. Mutation of human molybdenum cofactor sulfurase gene is responsible for classical xanthinuria type II. Ichida, K., Matsumura, T., Sakuma, R., Hosoya, T., Nishino, T. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  28. The human ET(B) endothelin receptor heterologously produced in the methylotrophic yeast Pichia pastoris shows high-affinity binding and induction of stacked membranes. Schiller, H., Haase, W., Molsberger, E., Janssen, P., Michel, H., Reiländer, H. Recept. Channels (2000) [Pubmed]
  29. Cell biology of molybdenum. Mendel, R.R., Bittner, F. Biochim. Biophys. Acta (2006) [Pubmed]
  30. [Expression and characterization of human vascular endothelial growth factor in Pichia pastoris]. Ma, L., Zhang, Z., Chen, A. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi (2000) [Pubmed]
  31. Developmental changes of aldehyde oxidase activity in young Japanese children. Tayama, Y., Miyake, K., Sugihara, K., Kitamura, S., Kobayashi, M., Morita, S., Ohta, S., Kihira, K. Clin. Pharmacol. Ther. (2007) [Pubmed]
  32. Electrooxidation mechanism of biogenic amines at amine oxidase modified graphite electrode. Niculescu, M., Ruzgas, T., Nistor, C., Frébort, I., Sebela, M., Pec, P., Csöregi, E. Anal. Chem. (2000) [Pubmed]
  33. Isolation and characterization of the human aldehyde oxidase gene: conservation of intron/exon boundaries with the xanthine oxidoreductase gene indicates a common origin. Terao, M., Kurosaki, M., Demontis, S., Zanotta, S., Garattini, E. Biochem. J. (1998) [Pubmed]
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