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The role of aldehyde oxidase in drug metabolism
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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“Although the function of AO in mammals is yet to be established (434, 935), AO appears to play an important role in drug metabolism and other metabolic pathways (335, 512, 513, 756, 920).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [335]
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Modern advances in heterocyclic chemistry in drug discovery
Taylor, A. P., Robinson, R. P., Fobian, Y. M., Blakemore, D. C., Jones, L. H., & Fadeyi, O. (2016) · Organic & Biomolecular Chemistry · doi:10.1039/c6ob00936k · Cited by 903
Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation
Tejero, J., Shiva, S., & Gladwin, M. T. (2019) · Physiological Reviews · doi:10.1152/physrev.00036.2017 · Cited by 541
Fan, J., & de Lannoy, I. A. M. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2013.09.007 · Cited by 309
The role of drug metabolizing enzymes in clearance
Di, L. (2014) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.2014.876006 · Cited by 216
Laskar, A. A., & Younus, H. (2018) · Drug Metabolism Reviews · doi:10.1080/03602532.2018.1555587 · Cited by 202
Metadata
- Authors
- Garattini, E., & Terao, M.
- Affiliations
- Mario Negri Institute for Pharmacological Research (IT)
- 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
- 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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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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