Aldehyde oxidase

Definition:

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.

References:

[1]. Tobias Hartmann, et al. The impact of single nucleotide polymorphisms on human aldehyde oxidase. Drug Metab Dispos. 2012 May;40(5):856-64. [Content Brief]

[2]. John T Barr, et al. Evidence for substrate-dependent inhibition profiles for human liver aldehyde oxidase. Drug Metab Dispos. 2013 Jan;41(1):24-9. [Content Brief]

[3]. Catarina Coelho, et al. Structural insights into xenobiotic and inhibitor binding to human aldehyde oxidase. Nat Chem Biol. 2015 Oct;11(10):779-83. [Content Brief]

[4]. J Matthew Hutzler, et al. Characterization of aldehyde oxidase enzyme activity in cryopreserved human hepatocytes. Drug Metab Dispos. 2012 Feb;40(2):267-75. [Content Brief]

[5]. Michael Zientek, et al. In vitro-in vivo correlation for intrinsic clearance for drugs metabolized by human aldehyde oxidase. Drug Metab Dispos. 2010 Aug;38(8):1322-7. [Content Brief]

[6]. M R Rashidi, et al. 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. [Content Brief]

[7]. Cexiong Fu, et al. 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. [Content Brief]

[8]. Timothy J Strelevitz, et al. 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. [Content Brief]

[9]. C Beedham, et al. 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. [Content Brief]

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