The role of aldehyde oxidase in drug metabolism

Expert Opin Drug Metab Toxicol. 2012 Apr;8(4):487-503. doi: 10.1517/17425255.2012.663352. Epub 2012 Feb 16.


Introduction: Aldehyde oxidases (AOXs) are molybdo-flavoenzymes with complex evolutionary profiles, as the number and types of active AOX genes vary according to the animal species considered. Humans and higher primates have a single functional AOX1 gene, while rodents are endowed with four AOXs. Along with the endoplasmic cytochrome P450 system (CYP450), cytoplasmic AOX1 is the major enzyme involved in the hepatic phase I metabolism of numerous xenobiotics.

Areas covered: The authors review literature to highlight the fact that aldehydes are not the only AOX substrates, as aza- and oxo-heterocycles, that represent the scaffold of many drugs, are also oxidized efficiently by these enzymes. Additionally, the ndefine the different complements of AOX isoenzymes expressed in humans and animal models used in drug metabolism studies and discuss the implications. Furthermore, the authors report on human AOX1 allelic variants that alter the activity of this enzyme. Finally, they discuss the factors of potential importance in controlling the functional activity of AOX1.

Expert opinion: There is evidence for an increasing relevance of AOX1 in the metabolism and clearance of new drugs, as measures aiming at controlling CYP450-dependent metabolism of prospective therapeutic agents are becoming routine. This calls for investigations into the biology, catalytic properties and substrate specificity of human AOX1.

Publication types

  • Review

MeSH terms

  • Aldehyde Oxidase / genetics
  • Aldehyde Oxidase / metabolism*
  • Aldehydes / metabolism
  • Alleles
  • Animals
  • Drug Discovery
  • Humans
  • Isoenzymes
  • Pharmaceutical Preparations / metabolism*
  • Species Specificity
  • Substrate Specificity
  • Xenobiotics / metabolism


  • Aldehydes
  • Isoenzymes
  • Pharmaceutical Preparations
  • Xenobiotics
  • AOX1 protein, human
  • Aldehyde Oxidase