Cited by 187Pharmacogenetics and Drug MetabolismDrug-Induced Hepatotoxicity and ProtectionMetal-Catalyzed Oxygenation Mechanisms

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The role of aldehyde oxidase in drug metabolism

Garattini, Enrico, Terao, Mineko·2012·Expert Opinion on Drug Metabolism & Toxicology

DOI 10.1517/17425255.2012.663352

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Abstract

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.

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Authors: Garattini, E., & Terao, M.
Affiliations: Mario Negri Institute for Pharmacological Research (IT)
ORCID: Garattini, Enrico
Terao, Mineko
Venue: Expert Opinion on Drug Metabolism & Toxicology
Publisher: Informa UK Limited
Published: 2012-02-16
Volume: 8
Issue: 4
Pages: 487-503
ISSN: 1742-5255 (ISSN-L)
1744-7607
DOI: 10.1517/17425255.2012.663352
OpenAlex: W2156168853
Cited by: 174
References: 102
Citations by year: 2026: 10 · 2025: 7 · 2024: 8 · 2023: 8 · 2022: 9 · 2021: 16 · 2020: 8 · 2019: 8 · 2018: 18 · 2017: 19 · 2016: 12 · 2015: 14 · 2014: 16 · 2013: 9 · 2012: 12
FWCI: 2.94
Type: journal article
Language: en
Open access: closed
Locations: Expert Opinion on Drug Metabolism & Toxicology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
Keywords: aldehyde oxidase, AOX1, drug metabolism, phase I metabolism, xenobiotic metabolism, aldehyde oxidation, cytochrome P450, hepatic clearance, substrate specificity
MeSH terms: Aldehydes, Alleles, Animals, Pharmaceutical Preparations, Humans, Isoenzymes, Species Specificity, Substrate Specificity, Xenobiotics, Aldehyde Oxidase, Drug Discovery

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The role of aldehyde oxidase in drug metabolism

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