Pair your accounts.

Export articles to Mendeley

Get article recommendations from ACS based on references in your Mendeley library.

Pair your accounts.

Export articles to Mendeley

Get article recommendations from ACS based on references in your Mendeley library.

You’ve supercharged your research process with ACS and Mendeley!

Click to create an ACS ID

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

Your Mendeley pairing has expired. Please reconnect
ACS Publications. Most Trusted. Most Cited. Most Read
My Activity

Figure 1Loading Img

Contribution of Aldehyde Oxidase, Xanthine Oxidase, and Aldehyde Dehydrogenase on the Oxidation of Aromatic Aldehydes

View Author Information
Department of Pharmaceutical Chemistry, School of Pharmacy, University of Bradford, Bradford, West Yorkshire BD7 1DP, United Kingdom, and School of Biochemistry and Biotechnology, University of Thessaly, 26 Ploutonos Street, Larissa 412 21, Greece
Cite this: Chem. Res. Toxicol. 2004, 17, 10, 1368–1376
Publication Date (Web):September 16, 2004
Copyright © 2004 American Chemical Society

    Article Views





    Other access options


    Abstract Image

    Aliphatic aldehydes have a high affinity toward aldehyde dehydrogenase activity but are relatively poor substrates of aldehyde oxidase and xanthine oxidase. In addition, the oxidation of xenobiotic-derived aromatic aldehydes by the latter enzymes has not been studied to any great extent. The present investigation compares the relative contribution of aldehyde dehydrogenase, aldehyde oxidase, and xanthine oxidase activities in the oxidation of substituted benzaldehydes in separate preparations. The incubation of vanillin, isovanillin, and protocatechuic aldehyde with either guinea pig liver aldehyde oxidase, bovine milk xanthine oxidase, or guinea pig liver aldehyde dehydrogenase demonstrated that the three aldehyde oxidizing enzymes had a complementary substrate specificity. Incubations were also performed with specific inhibitors of each enzyme (isovanillin for aldehyde oxidase, allopurinol for xanthine oxidase, and disulfiram for aldehyde dehydrogenase) to determine the relative contribution of each enzyme in the oxidation of these aldehydes. Under these conditions, vanillin was rapidly oxidized by aldehyde oxidase, isovanillin was predominantly metabolized by aldehyde dehydrogenase activity, and protocatechuic aldehyde was slowly oxidized, possibly by all three enzymes. Thus, aldehyde oxidase activity may be a significant factor in the oxidation of aromatic aldehydes generated from amines and alkyl benzenes during drug metabolism. In addition, this enzyme may also have a role in the catabolism of biogenic amines such as dopamine and noradrenaline where 3-methoxyphenylacetic acids are major metabolites.

    Read this article

    To access this article, please review the available access options below.

    Get instant access

    Purchase Access

    Read this article for 48 hours. Check out below using your ACS ID or as a guest.


    Access through Your Institution

    You may have access to this article through your institution.

    Your institution does not have access to this content. You can change your affiliated institution below.


     To whom correspondence should be addressed. Address:  5 Tenedou Street, Platia Amerikis, Athens 112 57, Greece. Tel:  +30210-8649617. Fax:  +302410-565290. E-mail:  [email protected] and [email protected].

     University of Bradford.

     University of Thessaly.

    Cited By

    This article is cited by 52 publications.

    1. Nenad Manevski, Lloyd King, William R. Pitt, Fabien Lecomte, Francesca Toselli. Metabolism by Aldehyde Oxidase: Drug Design and Complementary Approaches to Challenges in Drug Discovery. Journal of Medicinal Chemistry 2019, 62 (24) , 10955-10994.
    2. Paola Vitaglione, Roberta Barone Lumaga, Rosalia Ferracane, Irena Radetsky, Ilario Mennella, Rita Schettino, Saul Koder, Eyal Shimoni, and Vincenzo Fogliano . Curcumin Bioavailability from Enriched Bread: The Effect of Microencapsulated Ingredients. Journal of Agricultural and Food Chemistry 2012, 60 (13) , 3357-3366.
    3. David C. Pryde, Deepak Dalvie, Qiyue Hu, Peter Jones, R. Scott Obach, and Thien-Duc Tran . Aldehyde Oxidase: An Enzyme of Emerging Importance in Drug Discovery. Journal of Medicinal Chemistry 2010, 53 (24) , 8441-8460.
    4. Rachel D. Crouch. Xanthine Oxidoreductase and Aldehyde Oxidases. 2024
    5. P.Y. Chouinard, C. Garon, Y. Lebeuf, S. Dufour, R. Gervais. Milk volatilome as affected by somatic cell count in Holstein cows. Animal - Open Space 2023, 2 , 100049.
    6. Hani Zaher, George Zhang. Use of Human Intestinal and Hepatic Tissue Fractions and Microbiome as Models in Assessment of Drug Metabolism and its Impact on Oral Bioavailability. 2023, 737-756.
    7. Robert S. Foti. Cytochrome P450 and Other Drug-Metabolizing Enzymes As Therapeutic Targets. Drug Metabolism and Disposition 2023, 51 (8) , 936-949.
    8. Eman A. Alabbad, Sajid Bashir, Jingbo Louise Liu. Efficient removal of direct yellow dye using chitosan crosslinked isovanillin derivative biopolymer utilizing triboelectric energy produced from homogeneous catalysis. Catalysis Today 2022, 400-401 , 132-145.
    9. Károly Kubicskó, Richárd D. Kovács, Ödön Farkas. Quantum chemical study of the hydrolysis of oxidized endogenous psychedelic N,N-dimethyltryptamine. Computational and Theoretical Chemistry 2022, 1214 , 113789.
    10. Xiaoyan Pang, Chongzhuang Tang, Runcong Guo, Xiaoyan Chen. Non-cytochrome P450 enzymes involved in the oxidative metabolism of xenobiotics: Focus on the regulation of gene expression and enzyme activity. Pharmacology & Therapeutics 2022, 233 , 108020.
    11. Elisa Vignali, Loredano Pollegioni, Giovanna Di Nardo, Francesca Valetti, Silvia Gazzola, Gianfranco Gilardi, Elena Rosini. Multi‐Enzymatic Cascade Reactions for the Synthesis of cis,cis ‐Muconic Acid. Advanced Synthesis & Catalysis 2022, 364 (1) , 114-123.
    12. Daniela Silva-Adaya, Carla Garza-Lombó, María E. Gonsebatt. Xenobiotic transport and metabolism in the human brain. NeuroToxicology 2021, 86 , 125-138.
    13. Kaori Matsumoto, Tetsuya Hasegawa, Kosuke Ohara, Tomoyo Kamei, Junichi Koyanagi, Masayuki Akimoto. Role of human flavin-containing monooxygenase (FMO) 5 in the metabolism of nabumetone: Baeyer–Villiger oxidation in the activation of the intermediate metabolite, 3-hydroxy nabumetone, to the active metabolite, 6-methoxy-2-naphthylacetic acid in vitro. Xenobiotica 2021, 51 (2) , 155-166.
    14. Károly Kubicskó, Ödön Farkas. Quantum chemical (QM:MM) investigation of the mechanism of enzymatic reaction of tryptamine and N , N -dimethyltryptamine with monoamine oxidase A. Organic & Biomolecular Chemistry 2020, 18 (47) , 9660-9674.
    15. Joanna Oracz, Ewa Nebesny, Dorota Zyzelewicz, Grazyna Budryn, Boguslawa Luzak. Bioavailability and metabolism of selected cocoa bioactive compounds: A comprehensive review. Critical Reviews in Food Science and Nutrition 2020, 60 (12) , 1947-1985.
    16. Deepak Dalvie, Li Di. Aldehyde oxidase and its role as a drug metabolizing enzyme. Pharmacology & Therapeutics 2019, 201 , 137-180.
    17. Sravani Adusumalli, Rohitash Jamwal, R. Scott Obach, Tim F. Ryder, Lorenzo Leggio, Fatemeh Akhlaghi. Role of Molybdenum-Containing Enzymes in the Biotransformation of the Novel Ghrelin Receptor Inverse Agonist PF-5190457: A Reverse Translational Bed-to-Bench Approach. Drug Metabolism and Disposition 2019, 47 (8) , 874-882.
    18. J.Y. Cui, C.Y. Li. Regulation of Xenobiotic Metabolism in the Liver. 2018, 168-214.
    19. E. Garattini, M. Terao. Xanthine Oxidoreductase and Aldehyde Oxidases. 2018, 208-232.
    20. Florian Meyer, Hilke Pupkes, Alexander Steinbüchel, . Development of an Improved System for the Generation of Knockout Mutants of Amycolatopsis sp. Strain ATCC 39116. Applied and Environmental Microbiology 2017, 83 (3)
    21. Gholamreza Khamisipour, Farhad Jadidi-Niaragh, Abdolreza Sotoodeh Jahromi, Keivan zandi, Mohammad Hojjat-Farsangi. Mechanisms of tumor cell resistance to the current targeted-therapy agents. Tumor Biology 2016, 37 (8) , 10021-10039.
    22. Meijuan Li, Fengqing Wang, Yühong Huang, Feifei Du, Chenchun Zhong, Olajide E. Olaleye, Weiwei Jia, Yanfen Li, Fang Xu, Jiajia Dong, Jian Li, Justin B. R. Lim, Buchang Zhao, Lifu Jia, Li Li, Chuan Li. Systemic Exposure to and Disposition of Catechols Derived from Salvia miltiorrhiza Roots (Danshen) after Intravenous Dosing DanHong Injection in Human Subjects, Rats, and Dogs. Drug Metabolism and Disposition 2015, 43 (5) , 679-690.
    23. H. Karlsen, T. Dong. Biomarkers of urinary tract infections: state of the art, and promising applications for rapid strip-based chemical sensors. Analytical Methods 2015, 7 (19) , 7961-7975.
    24. Piero Zanello. The competition between chemistry and biology in assembling iron–sulfur derivatives. Molecular structures and electrochemistry. Part II. {[Fe2S2](SγCys)4} proteins. Coordination Chemistry Reviews 2014, 280 , 54-83.
    25. Maryam Hamzeh‐Mivehroud, Seifullah Rahmani, Mohammad‐Ali Hosseinpour Feizi, Siavoush Dastmalchi, Mohammad‐Reza Rashidi. In Vitro and In Silico Studies to Explore Structural Features of Flavonoids for Aldehyde Oxidase Inhibition. Archiv der Pharmazie 2014, 347 (10) , 738-747.
    26. John T. Barr, Kanika V. Choughule, Sahadev Nepal, Timothy Wong, Amarjit S. Chaudhry, Carolyn A. Joswig-Jones, Michael Zientek, Stephen C. Strom, Erin G. Schuetz, Kenneth E. Thummel, Jeffrey P. Jones. Why Do Most Human Liver Cytosol Preparations Lack Xanthine Oxidase Activity? . Drug Metabolism and Disposition 2014, 42 (4) , 695-699.
    27. Sheraz Tanoli, Nazish Tanoli, Saman Usmani, , Antonio Ferreira. The exploration of interaction studies of smaller size, mostly ignored yet intrinsically inestimable molecules towards BSA; An example of STD and DOSY NMR. Open Chemistry 2014, 12 (3) , 332-340.
    28. Ramakrishna Nirogi, Vishwottam Kandikere, Raghava Choudary Palacharla, Gopinadh Bhyrapuneni, Vijaya Bhargava Kanamarlapudi, Ranjith Kumar Ponnamaneni, Arun Kumar Manoharan. Identification of a suitable and selective inhibitor towards aldehyde oxidase catalyzed reactions. Xenobiotica 2014, 44 (3) , 197-204.
    29. Khaled S. Al salhen. In vitro oxidation of aldehyde oxidase from rabbit liver: Specificity toward endogenous substrates. Journal of King Saud University - Science 2014, 26 (1) , 67-74.
    30. Fidelis Ifeakachuku Achuba. Petroleum Products in Soil Mediated Oxidative Stress in Cowpea (Vigna unguiculata) and Maize (Zea mays) Seedlings. Open Journal of Soil Science 2014, 04 (12) , 417-435.
    31. Enrico Garattini, Mineko Terao. Aldehyde oxidase and its importance in novel drug discovery: present and future challenges. Expert Opinion on Drug Discovery 2013, 8 (6) , 641-654.
    32. John T. Barr, Jeffrey P. Jones. Evidence for Substrate-Dependent Inhibition Profiles for Human Liver Aldehyde Oxidase. Drug Metabolism and Disposition 2013, 41 (1) , 24-29.
    33. Jan Frömmel, Miroslav Soural, Martina Tylichová, David Kopečný, Gabriel Demo, Michaela Wimmerová, Marek Šebela. Plant aminoaldehyde dehydrogenases oxidize a wide range of nitrogenous heterocyclic aldehydes. Amino Acids 2012, 43 (3) , 1189-1202.
    34. Carolina Säll, J. Brian Houston, Aleksandra Galetin. A Comprehensive Assessment of Repaglinide Metabolic Pathways: Impact of Choice of In Vitro System and Relative Enzyme Contribution to In Vitro Clearance. Drug Metabolism and Disposition 2012, 40 (7) , 1279-1289.
    35. Michael Zientek, Ping Kang, Matthew J. Hutzler, Scott R. Obach. Molybdenum‐Containing Hydroxylases. 2012, 1-59.
    36. Enrico Garattini, Mineko Terao. The role of aldehyde oxidase in drug metabolism. Expert Opinion on Drug Metabolism & Toxicology 2012, 8 (4) , 487-503.
    37. Chrysoula Spanou, Aristidis S. Veskoukis, Thalia Kerasioti, Maria Kontou, Apostolos Angelis, Nektarios Aligiannis, Alexios-Leandros Skaltsounis, Dimitrios Kouretas, . Flavonoid Glycosides Isolated from Unique Legume Plant Extracts as Novel Inhibitors of Xanthine Oxidase. PLoS ONE 2012, 7 (3) , e32214.
    38. C. Beedham. Xanthine Oxidoreductase and Aldehyde Oxidase*. 2010, 185-205.
    39. Ping Liu, Sun Liang, Ben-Jie Wang, Rui-Chen Guo. Construction of expression system of rabbit aldehyde oxidase cDNA for the clarification of species differences. European Journal of Drug Metabolism and Pharmacokinetics 2009, 34 (3-4) , 205-211.
    40. Kunio Itoh, Mayuko Adachi, Jun Sato, Kanako Shouji, Kensuke Fukiya, Keiko Fujii, Yorihisa Tanaka. Effects of Selenium Deficiency on Aldehyde Oxidase 1 in Rats. Biological and Pharmaceutical Bulletin 2009, 32 (2) , 190-194.
    41. Mineko Terao, Mami Kurosaki, Maria Monica Barzago, Maddalena Fratelli, Renzo Bagnati, Antonio Bastone, Chiara Giudice, Eugenio Scanziani, Alessandra Mancuso, Cecilia Tiveron, Enrico Garattini. Role of the Molybdoflavoenzyme Aldehyde Oxidase Homolog 2 in the Biosynthesis of Retinoic Acid: Generation and Characterization of a Knockout Mouse. Molecular and Cellular Biology 2009, 29 (2) , 357-377.
    42. Mohammad-Hossein Sorouraddin, Ebrahim Fooladi, Abdolhossein Naseri, Mohammad-Reza Rashidi. A novel spectrophotometric method for determination of kinetic constants of aldehyde oxidase using multivariate calibration method. Journal of Biochemical and Biophysical Methods 2008, 70 (6) , 999-1005.
    43. Goutam Chowdhury, Venkatraman Junnotula, J. Scott Daniels, Marc M. Greenberg, Kent S. Gates. DNA Strand Damage Product Analysis Provides Evidence That the Tumor Cell-Specific Cytotoxin Tirapazamine Produces Hydroxyl Radical and Acts as a Surrogate for O 2. Journal of the American Chemical Society 2007, 129 (42) , 12870-12877.
    44. Bernard Testa, Stefanie D. Krämer. The Biochemistry of Drug Metabolism – An Introduction. Chemistry & Biodiversity 2007, 4 (3) , 257-405.
    45. O. Golubnitschaja, M. Fountoulakis. Gene Hunting by Substractive Hybridization in Down Syndrome Correlation with Proteomics Analysis. 2007, 345-358.
    46. Margherita Strolin Benedetti, Rhys Whomsley, Eugène Baltes. Involvement of enzymes other than CYPs in the oxidative metabolism of xenobiotics. Expert Opinion on Drug Metabolism & Toxicology 2006, 2 (6) , 895-921.
    47. Aristidis S. Veskoukis, Demetrios Kouretas, Georgios I. Panoutsopoulos. Substrate specificity of guinea pig liver aldehyde oxidase and bovine milk xanthine oxidase for methyl- and nitrobenzaldehydes. European Journal of Drug Metabolism and Pharmacokinetics 2006, 31 (1) , 11-16.
    48. Georgios I. Panoutsopoulos. Contribution of Aldehyde Oxidizing Enzymes on the Metabolism of 3,4-Dimethoxy-2-phenylethylamine to 3,4-Dimethoxyphenylacetic Acid by Guinea Pig Liver Slices. Cellular Physiology and Biochemistry 2006, 17 (1-2) , 47-56.
    49. Georgios I. Panoutsopoulos. Phenylacetaldehyde Oxidation by Freshly Prepared and Cryopreserved Guinea Pig Liver Slices: The Role of Aldehyde Oxidase. International Journal of Toxicology 2005, 24 (2) , 103-109.
    50. Georgios Panoutsopoulos, Christine Beedham. Enzymatic Oxidation of Vanillin, Isovanillin and Protocatechuic Aldehyde with Freshly Prepared Guinea Pig Liver Slices. Cellular Physiology and Biochemistry 2005, 15 (1-4) , 089-098.
    51. Georgios Panoutsopoulos. Metabolism of Homovanillamine to Homovanillic Acid in Guinea Pig Liver Slices. Cellular Physiology and Biochemistry 2005, 15 (5) , 225-232.
    52. Georgios I. Panoutsopoulos, Demetrios Kouretas, Elias G. Gounaris, Christine Beedham. Enzymatic Oxidation of 2‐Phenylethylamine to Phenylacetic Acid and 2‐Phenylethanol with Special Reference to the Metabolism of its Intermediate Phenylacetaldehyde. Basic & Clinical Pharmacology & Toxicology 2004, 95 (6) , 273-279.