Clinical Significance of Glutamate Dehydrogenase 2,  Sirtuin 4, some Elements in Epileptic Patients

Snowber M. Ahmed; Zeyan A. Ali

doi:10.14500/aro.12777

Authors

Snowber M. Ahmed Department of General Science, College of Basic Education, Salahaddin University-Erbil, Kurdistan Region, Iraq https://orcid.org/0000-0002-0162-1699
Zeyan A. Ali Department of Chemistry, College of Education, Salahaddin University-Erbil, Kurdistan Region, Iraq https://orcid.org/0000-0001-8978-6377

DOI:

https://doi.org/10.14500/aro.12777

Keywords:

Electrolytes, Epilepsy, Glutamate dehydrogenase 2, NAD-dependent ADP-ribosyltransferase sirtuin 4, Trace elements

Abstract

Epilepsy is a neurological condition caused by an imbalance of excitation and inhibition in the brain. Many factors influence this imbalance, including enzymes involved in producing neurotransmitters, the balance of electrolytes, and the effect of trace elements. The importance of this research lies in assessing the levels of these enzymes in human blood serum, unlike the common research specially in Kurdistan Thus, this study aimed to investigate the levels of glutamate dehydrogenase 2 (GDH2), NAD-dependent ADP-ribosyl transferase sirtuin 4 (SIRT4), electrolyte (Na, K, and Cl), and trace elements (Zn, Cu, and Se) in epileptic patients and compare them with control groups. The blood serum from 30 focal epilepsy (FE), generalized epilepsy (GE) patients, and 30 control groups was collected in Erbil city Hospital. The results of GDH2, SIRT4, Na, Zn, and Se may be utilized as parameters for detecting epileptic patients.

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Author Biographies

Snowber M. Ahmed, Department of General Science, College of Basic Education, Salahaddin University-Erbil, Kurdistan Region, Iraq

Snowber M. Ahmed is a lecturer at the Department of General Science , College of Basic Education, Salahaddin University-Erbil. She got the B.Sc. degree in Chemistry, the M.Sc. degree in Bbiochemistry. Recently, she is a Ph.D. student in clinical chemistry in the chemistry department of the College of Education. Her research interests are in the fields of neurology, gene therapy for neurological disease, and AI in neurological diagnosis.

Zeyan A. Ali, Department of Chemistry, College of Education, Salahaddin University-Erbil, Kurdistan Region, Iraq

Zeyan A. Ali is an Assistant Professor at the Department of Chemistry, College of Education, Salahaddin University-Erbil, Kurdistan Region, Iraq.

References

Abualrob, M.A., Itbaisha, A., and Mesraoua, B., 2025. Unlocking new frontiers in epilepsy through AI: From seizure prediction to personalized medicine. Epilepsy Behavior, 166, p.110327. DOI: https://doi.org/10.1016/j.yebeh.2025.110327

Aizaz, F., Khan, M.I., and Tiwari, S., 2024. Study of correlation between electrolyate imbalance and seizures in criticallly ill patients. Asian Journal of Pharmaceutical and Clinical Research, 17(1), pp.157-159.

Al Omairi, N.E., Albrakati, A., Alsharif, K.F., Almalki, A.S., Alsanie, W., Abd Elmageed, Z.Y., Zaafar, D., Lokman, M.S., Bauomy, A.A., Belal, S.K., Abdel-daim, M.M., Abdel Moneim, A.E., Alyami, H., and Kassab, R.B., 2022. Selenium nanoparticles with prodigiosin rescue hippocampal damage associated with epileptic seizures induced by pentylenetetrazole in rats. Biology (Basel), 11(3), p.354. DOI: https://doi.org/10.3390/biology11030354

Aman-Mohammady, A., Saadat, P., Qujeq, D., Hajian-Tilaki, K., and Saleki, K., 2023. Determination of plasma transcobalamin-II and zinc levels in newly-diagnosed and long-standing grand mal epileptic patients. Caspian Journal of Internal Medicine, 14(2), pp.199-204.

Andersen, J.V., 2025. The glutamate/GABA-glutamine cycle: Insights, updates, and advances. Journal of Neurochemistry, 169(3), p.e70029. DOI: https://doi.org/10.1111/jnc.70029

Andersen, J.V., and Schousboe, A., 2023. Milestone review: Metabolic dynamics of glutamate and GABA mediated neurotransmission - the essential roles of astrocytes. Journal of Neurochemistry, 166(2), pp.109-137. DOI: https://doi.org/10.1111/jnc.15811

Betsinger, C.N., and Cristea, I.M., 2019. Mitochondrial function, metabolic regulation, and human disease viewed through the prism of sirtuin 4 (SIRT4) functions. Journal of Proteome Research, 18(5), pp.1929-1938. DOI: https://doi.org/10.1021/acs.jproteome.9b00086

Chen, S., Huang, W., Xu, Q., He, T., Zhang, M., and Xu, H., 2023. The impact of serum copper on the risk of epilepsy: A mendelian randomization study. Acta Epileptologica, 5(1), p.15. DOI: https://doi.org/10.1186/s42494-023-00126-3

Dlugosz, A., Wroblewski, M., Blaszak, B., and Szulc, J., 2025. The Role of nutrition, oxidative stress, and trace elements in the pathophysiology of autism spectrum disorders. International Journal of Molecular Sciences, 26(2), p.808. DOI: https://doi.org/10.3390/ijms26020808

Domańska, N., Bojarska, M., Bogucka, J., Brzyska, A., Kosowska, M., and Piecewicz-Szczęsna, H., 2025. Beyond the seizures: Ketogenic Diets in the battle against drug-resistant epilepsy. Journal of Education Health and Sport, 77, p.56870. DOI: https://doi.org/10.12775/JEHS.2025.77.56870

Drews, L., Zimmermann, M., Westhoff, P., Brilhaus, D., Poss, R.E., Bergmann, L., Wiek, C., Brenneisen, P., Piekorz, R.P., Mettler-Altmann, T., Weber, A.P.M., and Reichert, A.S., 2020. Ammonia inhibits energy metabolism in astrocytes in a rapid and glutamate dehydrogenase 2-dependent manner. Disease Models and Mechanisms, 13(10), p.dmm047134. DOI: https://doi.org/10.1242/dmm.047134

Eissa, M.A., Abdulghani, K.O., Nada, M.A., Elkhawas, H.M., Shouman, A.E., and Ahmed, N.S., 2020. Serum zinc and copper levels in a sample of Egyptian epileptic children. The Egyptian Journal of Neurology Psychiatry and Neurosurgery, 56(1), p.79. DOI: https://doi.org/10.1186/s41983-020-00210-2

Fagerli, E., Escobar, I., Ferrier, F.J., Jackson, C.W., Perez-Lao, E.J., and Perez-Pinzon, M.A., 2022. Sirtuins and cognition: Implications for learning and memory in neurological disorders. Frontiers in Physiology, 13, p.908689. DOI: https://doi.org/10.3389/fphys.2022.908689

Fan, H., Wang, K., Zhao, X., Song, B., Yao, T., Liu, T., Gao, G., Lu, W., and Liu, C., 2024. Emerging insights into cuproptosis and copper metabolism: Implications for age-related diseases and potential therapeutic strategies. Frontiers in Aging Neuroscience, 16, p.1335122. DOI: https://doi.org/10.3389/fnagi.2024.1335122

Gruenbaum, B.F., Schonwald, A., Boyko, M., and Zlotnik, A., 2024. The role of glutamate and blood-Brain Barrier Disruption as a Mechanistic Link between Epilepsy and Depression. Cells, 13(14), p.1228. DOI: https://doi.org/10.3390/cells13141228

Han, Y., Zhou, S., Coetzee, S., and Chen, A., 2019. SIRT4 and its roles in energy and redox metabolism in health, disease and during exercise. Frontiers in Physiology, 10(9), p.1006. DOI: https://doi.org/10.3389/fphys.2019.01006

Howard, R., Baheerathan, A., Brown, R., Spillane, J., and Waraich, M., 2025. Neurological aspects of electrolyte disorders. Practical Neurology, 25, pp.303-312. DOI: https://doi.org/10.1136/pn-2023-003801

Huang, J., Yang, J., Miao, J., and Wen, H., 2023. Changes in routine blood parameters of patients with generalized tonic clonic seizure: A retrospective study. Neurosciences (Riyadh), 28(2), pp.123-129. DOI: https://doi.org/10.17712/nsj.2023.2.20220135

Kakkar, A.K., Gulati, S., Sarangi, S.C., and Gupta, Y.K., 2020. Effects of long term antiepileptic therapy on serum trace element levels in epileptic children. Interdisciplinary Toxicology, 13(2), pp.65-71. DOI: https://doi.org/10.2478/intox-2020-0008

Kamlesh, K., Singh, P.K., and Srivastava, A., 2022. To study the prevalence of electrolyte imbalance in patients with seizures. Global Journal for Research Analysis, 11(4), pp.134-136.

Kravos, M., 2021. Glutamate dehydrogenase applicability in clinical practice. KEI Journals,Medical Research Archives, 9(3), pp.1-9. DOI: https://doi.org/10.18103/mra.v9i3.2350

Litso, I., Plaitakis, A., Fadouloglou, V.E., Providaki, M., Kokkinidis, M., and Zaganas, I., 2023. Structural evolution of primate glutamate dehydrogenase 2 as revealed by in silico predictions and experimentally determined structures. Biomolecules, 14(1), p.22. DOI: https://doi.org/10.3390/biom14010022

Liu, W., Xu, J., Zhang, L., Li, F., Zhang, L., Tai, Z., Yang, J., Zhang, H., Tuo, J., Yu, C., and Xu, Z., 2023. Research progress on correlations between trace element levels and epilepsy. Frontiers in Cell and Developmental Biology, 11, p.1167626. DOI: https://doi.org/10.3389/fcell.2023.1167626

Milne-Ives, M., Brownson-Smith, R., Ananthakrishnan, A., Wang, Y., Cong, C., Winston, G.P., and Meinert, E., 2025. The use of AI in epilepsy and its applications for people with intellectual disabilities: Commentary. Acta Epileptologica, 7(1), p.13. DOI: https://doi.org/10.1186/s42494-025-00205-7

Nair, P.P., Aghoram, R., and Khilari, M.L., 2021. Applications of artificial intelligence in epilepsy. International Journal of Advanced Medical and Health Research, 8(2), pp.41-48. DOI: https://doi.org/10.4103/ijamr.ijamr_94_21

Netravathi, B.S., Ashrit, P., and Patil, R., 2025. To estimate prevalence and type of electrolyte abnormalities in adult patients with new onset seizures in a tertiary care. Journal of Population Therapeutics and Clinical Pharmacology, 32(1), pp.640-647. DOI: https://doi.org/10.53555/0xvv7t81

Plaitakis, A., Kalef-Ezra, E., Kotzamani, D., Zaganas, I., and Spanaki, C., 2017. The glutamate dehydrogenase pathway and its roles in cell and tissue biology in health and disease. Biology (Basel), 6(1),p.11. DOI: https://doi.org/10.3390/biology6010011

Qiao, Y.N., Li, L., Hu, S.H., Yang, Y.X., Ma, Z.Z., Huang, L., An, Y.P., Yuan, Y.Y., Lin, Y., Xu, W., Li, Y., Lin, P.C., Cao, J., Zhao, J.Y., and Zhao, S.M., 2024. Ketogenic diet-produced β-hydroxybutyric acid accumulates brain GABA and increases GABA/glutamate ratio to inhibit epilepsy. Cell Discovery, 10(1), p.46. DOI: https://doi.org/10.1038/s41421-024-00669-w

Ran, L., Xu, M., Zhang, Z., and Zeng, X., 2024. The association of nutrient intake with epilepsy: A cross-sectional study from NHANES, 2013-2014. Epilepsy Research, 200, p.107297. DOI: https://doi.org/10.1016/j.eplepsyres.2024.107297

Ruhling, M.R., Hartmann, H., and Das, A.M., 2024. Simplification of dietary treatment in pharmacoresistant epilepsy: Impact of c8 and c10 fatty acids on sirtuins of neuronal cells in vitro. Nutrients, 16(11), p.1678. DOI: https://doi.org/10.3390/nu16111678

Sar, G., Kılıç, A., Ilgen Uslu, F., Selek, Ş., Ustunova, S., and Meral, I., 2023. Serum electrolyte values and blood oxidative stress parameters in patients with focal and generalized epilepsy. Eastern Journal of Medicine, 28(1), pp.94-98. DOI: https://doi.org/10.5505/ejm.2023.93195

Shi, Y., Wei, Z., Feng, Y., Gan, Y., Li, G., and Deng, Y., 2024. Disorders of organic acid metabolism and epilepsy. Acta Epileptologica, 6(1), p.24. DOI: https://doi.org/10.1186/s42494-024-00167-2

Tavasoli, A., Afsharkhas, L., and Parvini, B., 2024. Evaluating the serum levels of zinc, copper, magnesium, and 25-hydroxy vitamin D in children with idiopathic drug-resistant epilepsy; a cross-sectional study. BMC Pediatrics, 24(1), p.518. DOI: https://doi.org/10.1186/s12887-024-04968-9

Tomaselli, D., Steegborn, C., Mai, A., and Rotili, D., 2020. Sirt4: A multifaceted enzyme at the crossroads of mitochondrial metabolism and cancer. Frontiers in Oncology, 10, p.474. DOI: https://doi.org/10.3389/fonc.2020.00474

Wang, X., Zhong, J., Lei, T., Chen, D., Wang, H., Zhu, L., Chu, S., and Liu, L., 2021. An artificial neural network prediction model for posttraumatic epilepsy: Retrospective cohort study. Journal of Medical Internet Research, 23(8), p.e2590. DOI: https://doi.org/10.2196/25090

Wu, Q.J., Zhang, T.N., Chen, H.H., Yu, X.F., Lv, J.L., Liu, Y.Y., Liu, Y.S., Zheng, G., Zhao, J.Q., Wei, Y.F., Guo, J.Y., Liu, F.H., Chang, Q., Zhang, Y.X., Liu, C.G., and Zhao, Y.H., 2022. The sirtuin family in health and disease. Signal Transduction and Targeted Therapy, 7(1), p.402. DOI: https://doi.org/10.1038/s41392-022-01257-8

Xu, H., Liu, Y.Y., Li, L.S., and Liu, Y.S., 2023. Sirtuins at the crossroads between mitochondrial quality control and neurodegenerative diseases: Structure, regulation, modifications, and modulators. Aging and Disease, 14(3), pp.794-824. DOI: https://doi.org/10.14336/AD.2022.1123

Yalçın, G.D., and Colak, M., 2020. SIRT4 prevents excitotoxicity via modulating glutamate metabolism in glioma cells. Human and Experimental Toxicology, 39(7), pp.938-947. DOI: https://doi.org/10.1177/0960327120907142

Zeng, Z., Lin, C., Pan, C., Chen, Z., and Ruan, B.H., 2025. An alternative mechanism of glutamate dehydrogenase inhibition by EGCG: Promotion of protein degradation. Pharmaceuticals (Basel), 18(6), p.877. DOI: https://doi.org/10.3390/ph18060877

Zhu, F., Xiang, Y., and Zeng, L., 2021. Progress on mitochondrial silence information regulator family in epilepsy. Zhejiang Da Xue Xue Bao Yi Xue Ban, 50(3), pp.403-408. DOI: https://doi.org/10.3724/zdxbyxb-2021-0163