Structural highlightsFunctionAOXA_HUMAN Oxidase with broad substrate specificity, oxidizing aromatic azaheterocycles, such as N1-methylnicotinamide and N-methylphthalazinium, 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. Also may 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.[1] [2] [3] [4] [5] [6] [7] [8]
References
- ↑ Zientek M, Jiang Y, Youdim K, Obach RS. In vitro-in vivo correlation for intrinsic clearance for drugs metabolized by human aldehyde oxidase. Drug Metab Dispos. 2010 Aug;38(8):1322-7. doi: 10.1124/dmd.110.033555. Epub 2010 , May 5. PMID:20444863 doi:http://dx.doi.org/10.1124/dmd.110.033555
- ↑ Hutzler JM, Yang YS, Albaugh D, Fullenwider CL, Schmenk J, Fisher MB. Characterization of aldehyde oxidase enzyme activity in cryopreserved human hepatocytes. Drug Metab Dispos. 2012 Feb;40(2):267-75. doi: 10.1124/dmd.111.042861. Epub 2011 , Oct 26. PMID:22031625 doi:http://dx.doi.org/10.1124/dmd.111.042861
- ↑ Hartmann T, Terao M, Garattini E, Teutloff C, Alfaro JF, Jones JP, Leimkuhler S. The impact of single nucleotide polymorphisms on human aldehyde oxidase. Drug Metab Dispos. 2012 May;40(5):856-64. doi: 10.1124/dmd.111.043828. Epub 2012 , Jan 25. PMID:22279051 doi:http://dx.doi.org/10.1124/dmd.111.043828
- ↑ Strelevitz TJ, Orozco CC, Obach RS. Hydralazine as a selective probe inactivator of aldehyde oxidase in human hepatocytes: estimation of the contribution of aldehyde oxidase to metabolic clearance. Drug Metab Dispos. 2012 Jul;40(7):1441-8. doi: 10.1124/dmd.112.045195. Epub 2012 , Apr 20. PMID:22522748 doi:http://dx.doi.org/10.1124/dmd.112.045195
- ↑ Barr JT, Jones JP. Evidence for substrate-dependent inhibition profiles for human liver aldehyde oxidase. Drug Metab Dispos. 2013 Jan;41(1):24-9. doi: 10.1124/dmd.112.048546. Epub 2012, Sep 20. PMID:22996261 doi:http://dx.doi.org/10.1124/dmd.112.048546
- ↑ Fu C, Di L, Han X, Soderstrom C, Snyder M, Troutman MD, Obach RS, Zhang H. Aldehyde oxidase 1 (AOX1) in human liver cytosols: quantitative characterization of AOX1 expression level and activity relationship. Drug Metab Dispos. 2013 Oct;41(10):1797-804. doi: 10.1124/dmd.113.053082. Epub, 2013 Jul 15. PMID:23857892 doi:http://dx.doi.org/10.1124/dmd.113.053082
- ↑ Beedham C, Critchley DJ, Rance DJ. Substrate specificity of human liver aldehyde oxidase toward substituted quinazolines and phthalazines: a comparison with hepatic enzyme from guinea pig, rabbit, and baboon. Arch Biochem Biophys. 1995 Jun 1;319(2):481-90. PMID:7786031 doi:http://dx.doi.org/10.1006/abbi.1995.1320
- ↑ Rashidi MR, Smith JA, Clarke SE, Beedham C. In vitro oxidation of famciclovir and 6-deoxypenciclovir by aldehyde oxidase from human, guinea pig, rabbit, and rat liver. Drug Metab Dispos. 1997 Jul;25(7):805-13. PMID:9224775
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