ArticleDrug metabolism and disposition: the biological fate of chemicals2012
The impact of single nucleotide polymorphisms on human aldehyde oxidase.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 101 citations in OpenAlex.
- A systematic review of single nucleotide polymorphisms affecting allopurinol pharmacokinetics and serum uric acid level.Pharmacogenomics · 2024Pooled it
- Favipiravir pharmacokinetics in Ebola-Infected patients of the JIKI trial reveals concentrations lower than targeted.PLoS neglected tropical diseases · 2017Trial
- Structure of human aldehyde oxidase under tris(2-carboxyethyl)phosphine reducing conditions.Acta crystallographica. Section F, Structural biology communications · 2026Article
- Identification of PCSK9-like human gene knockouts using metabolomics, proteomics, and whole-genome sequencing in a consanguineous population.Cell genomics · 2023Article
- Considerations into pharmacogenomics of COVID-19 pharmacotherapy: Hope, hype and reality.Pulmonary pharmacology & therapeutics · 2022Review
- Biotransformation novel advances - 2021 year in review.Drug metabolism reviews · 2022Review
- Aldehyde Oxidase Contributes to All-Drug metabolism and disposition: the biological fate of chemicals · 2021Article
- Enzyme Kinetics, Pharmacokinetics, and Inhibition of Aldehyde Oxidase.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Functional mononuclear molybdenum enzymes: challenges and triumphs in molecular cloning, expression, and isolation.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2020Review
- Evolution, expression, and substrate specificities of aldehyde oxidase enzymes in eukaryotes.The Journal of biological chemistry · 2020Review
- Systematic exploration of predicted destabilizing nonsynonymous single nucleotide polymorphisms (nsSNPs) of human aldehyde oxidase: A Bio-informatics study.Pharmacology research & perspectives · 2019Article
- Human aldehyde oxidase (hAOX1): structure determination of the Moco-free form of the natural variant G1269R and biophysical studies of single nucleotide polymorphisms.FEBS open bio · 2019Article
- Survey of allele specific expression in bovine muscle.Scientific reports · 2019Article
- A novel in vitro allometric scaling methodology for aldehyde oxidase substrates to enable selection of appropriate species for traditional allometry.Xenobiotica; the fate of foreign compounds in biological systems · 2018Article
- Severe Delayed Drug Reactions: Role of Genetics and Viral Infections.Immunology and allergy clinics of North America · 2017Review
- ecoAO: A Simple System for the Study of Human Aldehyde Oxidases Role in Drug Metabolism.ACS omega · 2017Article
- The genetics of gout: towards personalised medicine?BMC medicine · 2017Review
- Genomic sequencing of uric acid metabolizing and clearing genes in relationship to xanthine oxidase inhibitor dose.Rheumatology international · 2017Article
- Distribution bias analysis of germline and somatic single-nucleotide variations that impact protein functional site and neighboring amino acids.Scientific reports · 2017Article
- A single nucleotide polymorphism causes enhanced radical oxygen species production by human aldehyde oxidase.PloS one · 2017Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
Aldehyde oxidase (AO) is a complex molybdo-flavoprotein that belongs to the xanthine oxidase family. AO is active as a homodimer, and each 150-kDa monomer binds two distinct [2Fe2S] clusters, FAD, and the molybdenum cofactor. AO has an important role in the metabolism of drugs based on its broad substrate specificity oxidizing aromatic aza-heterocycles, for example, N(1)-methylnicotinamide and N-methylphthalazinium, or aldehydes, such as benzaldehyde, retinal, and vanillin. Sequencing the 35 coding exons of the human AOX1 gene in a sample of 180 Italian individuals led to the identification of relatively frequent, synonymous, missense and nonsense single-nucleotide polymorphisms (SNPs). Human aldehyde oxidase (hAOX1) was purified after heterologous expression in Escherichia coli. The recombinant protein was obtained with a purity of 95% and a yield of 50 μg/l E. coli culture. Site-directed mutagenesis of the hAOX1 cDNA allowed the purification of protein variants bearing the amino acid changes R802C, R921H, N1135S, and H1297R, which correspond to some of the identified SNPs. The hAOX1 variants were purified and compared with the wild-type protein relative to activity, oligomerization state, and metal content. Our data show that the mutation of each amino acid residue has a variable impact on the ability of hAOX1 to metabolize selected substrates. Thus, the human population is characterized by the presence of functionally inactive hAOX1 allelic variants as well as variants encoding enzymes with different catalytic activities. Our results indicate that the presence of these allelic variants should be considered for the design of future drugs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.