Non-Competitive Inhibition of Xanthine Oxidase by N-Nitrosomorpholine: An In Vitro Study

Deniz Bakır; Serkan Kapancık

doi:10.17776/csj.1485123

EN

Non-Competitive Inhibition of Xanthine Oxidase by N-Nitrosomorpholine: An In Vitro Study

Abstract

Nitrosamines can be formed from nitrate. Nitrate is not actually toxic to mammals but can be reduced to nitrite. Nitrite, on the other hand, reacts with amino groups to form the carcinogenic N-nitroso compound. N-nitrosomorpholine (NMOR) is a carcinogenic compound that is included in the nitrosamine class and is the most common type of nitrosamines. Xanthine oxidase (XO) is an enzyme that catalyzes the hydroxylation of hypoxanthine to xanthine and xanthine to uric acid in purine metabolism. Excessive production and/or inadequate excretion of uric acid causes hyperuricemia. This condition is associated with kidney and cardiovascular diseases, especially gout. In order to prevent hyperuricemia and therefore gout, suppressing the activity of the XO enzyme is one of the main targets. In our study, the possible inhibitory effects of NMOR on the activity of the XO enzyme were investigated by spectrophotometric method. XO activity was evaluated in the presence of different concentrations of NMOR and analyzed using Lineweaver-Burk plot. The Km value was determined as 0.55 mM and the Vmax value was determined as 2.45 U/ml. Finally, it was determined that the XO enzyme was inhibited non-competitively by NMOR. Inhibition of XO enzyme with the help of NMOR may lead to functional deficiencies by disrupting the pathway in which purines are metabolized, as well as mediating the control of the production of uric acid formed in purine metabolism. More advanced methods and in vivo studies are needed to better understand the effects of NMOR on the organism and XO enzyme

Keywords

Supporting Institution

Yok

Project Number

Yok

Ethical Statement

Yazarlar arasında herhangi bir çıkar çatışması bulunmamaktadır.

Thanks

Yok

References

[1] Swann P.F., The toxicology of nitrate, nitrite and n‐nitroso compounds, Journal of the Science of Food and Agriculture, 26 (11) (1975) 1761-1770.
[2] Ozbay S., Sireli U.T., Filazi A., Nitrosamines, their chemistries and effects on health, Int. J. Sci. Technol. Res., 5 (4) (2019) 124-133.
[3] Deveci G., Tek N.A., N‐Nitrosamines: a potential hazard in processed meat products. Journal of the Science of Food and Agriculture, 104 (5) (2024) 2551-2560.
[4] Xie Y., Geng Y., Yao J., Ji J., Chen F., Xiao J., ... & Ma L., N-nitrosamines in processed meats: Exposure, formation and mitigation strategies. Journal of Agriculture and Food Research, 13 (2023) 100645.
[5] Li Y., Hecht S.S., Metabolic activation and DNA interactions of carcinogenic N-nitrosamines to which humans are commonly exposed, International journal of molecular sciences, 23 (9) (2022) 4559.
[6] Zhao B., Zhou J., Nakada N., Ihara M., Liu Y., Wong Y.J., ... & Tanaka H., COVID-19 impacts on characterization of N-nitrosamines and their precursors during transport in sewer systems, Water Research, 279 (2025) 123439.
[7] Meng X.J., Liu X.D., Zhang X.M., Hu Y., Guo Q.F.,. Determination of 8 N-nitrosamines in the workplace air by GC-MS/MS method, Chinese journal of industrial hygiene and occupational diseases, 42 (8) (2024) 616-620.
[8] Brunnemann K.D., Hoffmann D., Decreased concentrations of N-nitrosodiethanolamine and N-nitrosomorpholine in commercial tobacco products, Journal of agricultural and food chemistry, 39 (1) (1991) 207-208.

[9] Schmidtsdorff S., Neumann J., Schmidt A.H., Parr M.K., Prevalence of nitrosamine contaminants in drug samples: Has the crisis been overcome?, Archiv der Pharmazie, 356 (2) (2023) 2200484.
[10] Steinberg P., Klingelhöffer A., Schäfer A., Wüst G., Weisse G., Oesch F., Eigenbrodt E., Expression of pyruvate kinase M 2 in preneoplastic hepatic foci of N-nitrosomorpholine-treated rats, Virchows Archiv, 434 (1999) 213-220.
[11] Reznik-Schüller H., Sequential morphologic alterations in the bronchial epithelium of Syrian golden hamsters during N-nitrosomorpholine-induced pulmonary tumorigenesis, The American Journal of Pathology, 89 (1) (1977) 59.
[12] Gezer E., Özer C., Şimşek T., Yaprak Bayrak B., Turan G., Çetinarslan B., ... & Köksalan D., N-Nitrosomorpholine-induced oncocytic transformation in rat endocrine organs, European Journal of Medical Research, 29 (1) (2024) 64.
[13] Kostić D.A., Dimitrijević D.S., Stojanović G.S., Palić I.R., Đorđević A.S., Ickovski J.D., Xanthine oxidase: isolation, assays of activity, and inhibition, Journal of chemistry, 2015 (1) (2015) 294858.
[14] Hille R., Xanthine oxidase—a personal history, Molecules, 28 (4) (2023) 1921.
[15] Ullah Z., Yue P., Mao G., Zhang M., Liu P., Wu X., ... & Yang L., A comprehensive review on recent xanthine oxidase inhibitors of dietary based bioactive substances for the treatment of hyperuricemia and gout: Molecular mechanisms and perspective, International Journal of Biological Macromolecules, (2024) 134832.
[16] Massey V., Brumby P E., Komai H., Palmer G., Studies on milk xanthine oxidase: some spectral and kinetic properties, Journal of Biological Chemistry, 244 (7) (1969) 1682-1691.
[17] Masui T., Nakanishi H., Inada K.I., Imai T., Mizoguchi Y., Yada H., ... & Tatematsu M., Highly metastatic hepatocellular carcinomas induced in male F344 rats treated with N-nitrosomorpholine in combination with other hepatocarcinogens show a high incidence of p53 gene mutations along with altered mRNA expression of tumor-related genes, Cancer letters, 112 (1) (1997) 33-45.
[18] Alston T.A., Porter D.J., Bright H.J., Enzyme inhibition by nitro and nitroso compounds, Accounts of Chemical Research, 16 (11) (1983) 418-424.
[19] Singh A., Singh K., Sharma A., Kaur K., Chadha R., Bedi P.M.S., Past, present and future of xanthine oxidase inhibitors: design strategies, structural and pharmacological insights, patents and clinical trials, RSC Medicinal Chemistry, 14 (11) (2023) 2155-2191.
[20] Yu D., Du J., He P., Wang N., Li L., Liu Y., ... & Li Y., Identification of natural xanthine oxidase inhibitors: Virtual screening, anti-xanthine oxidase activity, and interaction mechanism, International Journal of Biological Macromolecules, 259 (2024) 129286.
[21] Onat T., Emerk K., Sözmen E., İnsan biyokimyası, Palme yayıncılık, (2002) 208.

Details

Primary Language

English

Subjects

Enzymes

Journal Section

Research Article

Authors

Deniz Bakır
0009-0001-6867-2431
Türkiye

Serkan Kapancık ^*
0000-0003-3019-4275
Türkiye

Publication Date

June 30, 2025

Submission Date

May 16, 2024

Acceptance Date

May 13, 2025

Published in Issue

Year 2025 Volume: 46 Number: 2

DOI

https://doi.org/10.17776/csj.1485123

IZ

https://izlik.org/JA86AZ29BZ

Cite

RIS / Bibtex

APA

Bakır, D., & Kapancık, S. (2025). Non-Competitive Inhibition of Xanthine Oxidase by N-Nitrosomorpholine: An In Vitro Study. Cumhuriyet Science Journal, 46(2), 264-267. https://doi.org/10.17776/csj.1485123

AMA

1.Bakır D, Kapancık S. Non-Competitive Inhibition of Xanthine Oxidase by N-Nitrosomorpholine: An In Vitro Study. CSJ. 2025;46(2):264-267. doi:10.17776/csj.1485123

Chicago

Bakır, Deniz, and Serkan Kapancık. 2025. “Non-Competitive Inhibition of Xanthine Oxidase by N-Nitrosomorpholine: An In Vitro Study”. Cumhuriyet Science Journal 46 (2): 264-67. https://doi.org/10.17776/csj.1485123.

EndNote

Bakır D, Kapancık S (June 1, 2025) Non-Competitive Inhibition of Xanthine Oxidase by N-Nitrosomorpholine: An In Vitro Study. Cumhuriyet Science Journal 46 2 264–267.

IEEE

[1]D. Bakır and S. Kapancık, “Non-Competitive Inhibition of Xanthine Oxidase by N-Nitrosomorpholine: An In Vitro Study”, CSJ, vol. 46, no. 2, pp. 264–267, June 2025, doi: 10.17776/csj.1485123.

ISNAD

Bakır, Deniz - Kapancık, Serkan. “Non-Competitive Inhibition of Xanthine Oxidase by N-Nitrosomorpholine: An In Vitro Study”. Cumhuriyet Science Journal 46/2 (June 1, 2025): 264-267. https://doi.org/10.17776/csj.1485123.

JAMA

1.Bakır D, Kapancık S. Non-Competitive Inhibition of Xanthine Oxidase by N-Nitrosomorpholine: An In Vitro Study. CSJ. 2025;46:264–267.

MLA

Bakır, Deniz, and Serkan Kapancık. “Non-Competitive Inhibition of Xanthine Oxidase by N-Nitrosomorpholine: An In Vitro Study”. Cumhuriyet Science Journal, vol. 46, no. 2, June 2025, pp. 264-7, doi:10.17776/csj.1485123.

Vancouver

1.Deniz Bakır, Serkan Kapancık. Non-Competitive Inhibition of Xanthine Oxidase by N-Nitrosomorpholine: An In Vitro Study. CSJ. 2025 Jun. 1;46(2):264-7. doi:10.17776/csj.1485123