ArticleDrug metabolism and disposition: the biological fate of chemicals2013
Evidence for substrate-dependent inhibition profiles for human liver aldehyde oxidase.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 40 citations in OpenAlex.
- Roles of selected non-P450 human oxidoreductase enzymes in protective and toxic effects of chemicals: review and compilation of reactions.Archives of toxicology · 2022Review
- In Vitro ADME and Preclinical Pharmacokinetics of Ulotaront, a TAAR1/5-HTPharmaceutical research · 2022Article
- Case Study 11: Considerations for Enzyme Mapping Experiments-Interaction Between the Aldehyde Oxidase Inhibitor Hydralazine and Glutathione.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Site-Directed Mutagenesis at the Molybdenum Pterin Cofactor Site of the Human Aldehyde Oxidase: Interrogating the Kinetic Differences Between Human and Cynomolgus Monkey.Drug metabolism and disposition: the biological fate of chemicals · 2020Article
- The Metabolic Rainbow: Deep Learning Phase I Metabolism in Five Colors.Journal of chemical information and modeling · 2020Article
- Time Course of Aldehyde Oxidase and Why It Is Nonlinear.Drug metabolism and disposition: the biological fate of chemicals · 2019Article
- Effects of Phenothiazines on Aldehyde Oxidase Activity Towards Aldehydes and N-Heterocycles: an In Vitro and In Silico Study.European journal of drug metabolism and pharmacokinetics · 2019Article
- Fast Methods for Prediction of Aldehyde Oxidase-Mediated Site-of-Metabolism.Computational and structural biotechnology journal · 2019Article
- Computationally Assessing the Bioactivation of Drugs by N-Dealkylation.Chemical research in toxicology · 2018Article
- Article
- ecoAO: A Simple System for the Study of Human Aldehyde Oxidases Role in Drug Metabolism.ACS omega · 2017Article
- Interspecies differences in the metabolism of methotrexate: An insight into the active site differences between human and rabbit aldehyde oxidase.Biochemical pharmacology · 2015Article
- A novel reaction mediated by human aldehyde oxidase: amide hydrolysis of GDC-0834.Drug metabolism and disposition: the biological fate of chemicals · 2015Article
- Inhibition of human aldehyde oxidase activity by diet-derived constituents: structural influence, enzyme-ligand interactions, and clinical relevance.Drug metabolism and disposition: the biological fate of chemicals · 2015Article
- In vitro oxidative metabolism of 6-mercaptopurine in human liver: insights into the role of the molybdoflavoenzymes aldehyde oxidase, xanthine oxidase, and xanthine dehydrogenase.Drug metabolism and disposition: the biological fate of chemicals · 2014Article
- Why do most human liver cytosol preparations lack xanthine oxidase activity?Drug metabolism and disposition: the biological fate of chemicals · 2014Article
- Inhibition of xanthine oxidase by the aldehyde oxidase inhibitor raloxifene: implications for identifying molybdopterin nitrite reductases.Nitric oxide : biology and chemistry · 2014Article
- Absolute quantification of aldehyde oxidase protein in human liver using liquid chromatography-tandem mass spectrometry.Molecular pharmaceutics · 2013Article
- Evaluation of rhesus monkey and guinea pig hepatic cytosol fractions as models for human aldehyde oxidase.Drug metabolism and disposition: the biological fate of chemicals · 2013Article
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2 authors at 1 institution in 1 country.
Funding
Abstract
The goal of this study was to provide a reasonable assessment of how probe substrate selection may impact the results of in vitro aldehyde oxidase (AO) inhibition experiments. Here, we used a previously studied set of seven known AO inhibitors to probe the inhibition profile of a pharmacologically relevant substrate N-[(2-dimethylamino)ethyl]acridine-4-carboxamide (DACA). DACA oxidation in human liver cytosol was characterized with a measured V(max) of 2.3 ± 0.08 nmol product · min(-1) · mg(-1) and a K(m) of 6.3 ± 0.8 µM. The K(ii) and K(is) values describing the inhibition of DACA oxidation by the panel of seven inhibitors were tabulated and compared with previous findings with phthalazine as the substrate. In every case, the inhibition profile shifted to a much less uncompetitive mode of inhibition for DACA relative to phthalazine. With the exception of one inhibitor, raloxifene, this change in inhibition profile seems to be a result of a decrease in the uncompetitive mode of inhibition (an affected K(ii) value), whereas the competitive mode (K(is)) seems to be relatively consistent between substrates. Raloxifene was found to inhibit competitively when using DACA as a probe, and a previous report showed that raloxifene inhibited uncompetitively with other substrates. The relevance of these data to the mechanistic understanding of aldehyde oxidase inhibition and potential implications on drug-drug interactions is discussed. Overall, it appears that the choice in substrate may be critical when conducting mechanistic inhibition or in vitro drug-drug interactions prediction studies with AO.
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