Clinical significance of Glutamate Dehydrogenase 2, Sirtuin 4 and some Electrolyte-Trace Elements in Epileptic patient
Clinical significance of enzymes and some Electrolyte-Trace Elements in Epileptic patient
DOI:
https://doi.org/10.14500/aro.12777Keywords:
Electrolytes, Epilepsy, Glutamate dehydrogenase 2, NAD-dependent ADP-ribosyltransferase sirtuin 4, Trace elementsAbstract
Epilepsy is a neurological condition that is 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. Thus, this study aimed to investigate the levels of glutamate dehydrogenase 2 (GDH2), NAD-dependent ADP-ribosyl transferase sirtuin 4 (SIRT4), electrolytes (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) patients, 30 generalized epilepsy (GE) patients, and 30 control groups was collected in Erbil City Hospital. The results of the study showed a significant decrease in GDH2 with a P < 0.0001 for the FE and GE groups. SIRT4 levels were significantly increased in both groups, compared to the control group. Furthermore, levels of Na, Zn, and Se were markedly reduced, while no significant variations were observed in K, Cl, and Cu levels between epileptic patients and control groups. The ROC curve and area under the curve (AUC) results for GDH2 (0.8092), SIRT4 (0.8956), sodium (0.8673), zinc (0.9711), and selenium (1). The results of the artificial neural networks showed that selenium, zinc, sodium, GDH2, and SIRT4 had the greatest impact on how the network classified patients as having epilepsy or being healthy. The results of GDH2, SIRT4, Na, Zn, and Se may be utilized as parameters for detecting the state of epileptic patients and used as beneficial biomarkers
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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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Howard, R., Baheerathan, A., Brown, R., Spillane, J., and Waraich, M., 2025. Neurological aspects of electrolyte disorders. Practical Neurology, 25, pp.303-312.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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Copyright (c) 2026 Snowber M. Ahmed, Zeyan A. Ali
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Accepted 2026-03-29
Published 2026-06-23
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