Pathophysiology, The Biochemical and Clinical Significance of Lactate Dehydrogenase

¹Mohammed Hasan Barrak, ²Farah Ali Dawood, ³Safa Nihad Abed Shubar, ⁴Ali A. Al-fahham

¹Department of Basic Science, College of Dentistry, Mustansiriah University, Baghdad, Iraq.

²Department of Basic Science, College of Dentistry, Mustansiriah University, Baghdad, Iraq.

³Al-Mussaib Technical Institute, Al-Furat Al-Awsat Technical University, Mussaib 51009, Iraq.

⁴Faculty of Nursing, University of Kufa, Iraq.

DOI : 10.58806/ijhmr.2024.v3i07n02

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ABSTRACT:

Lactate dehydrogenase (LDH) is a family of enzymes that catalyzes oxidation-reduction enzymes, the interconversion between pyruvic acid and lactic acid. It is an enzyme that terminates the final catabolic reaction in which glucose id hydrolyzes anaerobically (glycolysis) resulting in lactate from pyruvate. These varied biochemical characteristics significantly influence its specificity to cells, tissues, and organs. Although LDH is mainly found in the cytoplasm, it is also located in multiple organelles. The presence of blood LDH implies an enzyme marker, and it may be a sign of death for many conditions such as ARDS, severe COVID-19, and some cancers. When LDH levels in the blood are increased they can reflect liver disease or anemia plus heart attack in addition to bone fracture — and muscle trauma. This also includes cancerous formations; infections like encephalitis or meningitis — along with HIV.

REFERENCES :

1) Chen, J., & Zou, X. (2023). Prognostic significance of lactate dehydrogenase and its impact on the outcomes of gastric cancer: a systematic review and meta-analysis. Frontiers in oncology, 13, 1247444. https://doi.org/10.3389/fonc.2023.1247444
2) Farhana A and Lappin SL. (2023) Biochemistry, Lactate Dehydrogenase. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; Jan-. Available from:

https://www.ncbi.nlm.nih.gov/books/NBK557536/
3) Feng, Y., Xiong, Y., Qiao, T., Li, X., Jia, L., & Han, Y. (2018). Lactate dehydrogenase A: A key player in carcinogenesis and potential target in cancer therapy. Cancer medicine, 7(12), 6124–6136. https://doi.org/10.1002/cam4.1820
4) Forkasiewicz, A., Dorociak, M., Stach, K., Szelachowski, P., Tabola, R., & Augoff, K. (2020). The usefulness of lactate dehydrogenase measurements in current oncological practice. Cellular & molecular biology letters, 25, 35. https://doi.org/10.1186/s11658-020-00228-7
5) Gupta G. S. (2022). The Lactate and the Lactate Dehydrogenase in Inflammatory Diseases and Major Risk Factors in COVID-19 Patients. Inflammation, 45(6), 2091–2123. https://doi.org/10.1007/s10753-022-01680-7
6) Gupta GS. (2017) Lactate: Metabolic hallmark of cancer in 21st century. Clinics in Oncology.;2:1375–1377
7) Khan, A. A., Allemailem, K. S., Alhumaydhi, F. A., Gowder, S. J. T., & Rahmani, A. H. (2020). The Biochemical and Clinical Perspectives of Lactate Dehydrogenase: An Enzyme of Active Metabolism. Endocrine, metabolic & immune disorders drug targets, 20(6), 855–868. https://doi.org/10.2174/1871530320666191230141110
8) Livesey, A., Garty, F., Shipman, A. R., & Shipman, K. E. (2020). Lactate dehydrogenase in dermatology practice. Clinical and experimental dermatology, 45(5), 539–543. https://doi.org/10.1111/ced.14134
9) Mishra, D., & Banerjee, D. (2019). Lactate Dehydrogenases as Metabolic Links between Tumor and Stroma in the Tumor Microenvironment. Cancers, 11(6), 750.

https://doi.org/10.3390/cancers11060750
10) Mori, K., Kimura, S., Parizi, M. K., Enikeev, D. V., Glybochko, P. V., Seebacher, V., Fajkovic, H., Mostafaei, H., Lysenko, I., Janisch, F., Egawa, S., & Shariat, S. F. (2019). Prognostic Value of Lactate Dehydrogenase in Metastatic Prostate Cancer: A Systematic Review and Meta-analysis. Clinical genitourinary cancer, 17(6), 409–418.

https://doi.org/10.1016/j.clgc.2019.07.009
11) Passarella, S., & Schurr, A. (2018). l-Lactate Transport and Metabolism in Mitochondria of Hep G2 Cells-The Cori Cycle Revisited. Frontiers in oncology, 8, 120.

https://doi.org/10.3389/fonc.2018.00120
12) Passarella, S., & Schurr, A. (2018). l-Lactate Transport and Metabolism in Mitochondria of Hep G2 Cells-The Cori Cycle Revisited. Frontiers in oncology, 8, 120.

https://doi.org/10.3389/fonc.2018.00120
13) Qin, F., Li, J., Mao, T., Feng, S., Li, J., & Lai, M. (2023). 2 Hydroxybutyric Acid-Producing Bacteria in Gut Microbiome and Fusobacterium nucleatum Regulates 2 Hydroxybutyric Acid Level In Vivo. Metabolites, 13(3), 451. https://doi.org/10.3390/metabo13030451
14) Read, J. A., Winter, V. J., Eszes, C. M., Sessions, R. B., & Brady, R. L. (2001). Structural basis for altered activity of M- and H-isozyme forms of human lactate dehydrogenase. Proteins, 43(2), 175–185. https://doi.org/10.1002/1097-0134(20010501)43:2<175::aid-prot1029>3.0.co;2-#
15) Schurr, A., & Payne, R. S. (2007). Lactate, not pyruvate, is neuronal aerobic glycolysis end product: an in vitro electrophysiological study. Neuroscience, 147(3), 613–619. https://doi.org/10.1016/j.neuroscience.2007.05.002
16) Shi, Y., & Pinto, B. M. (2014). Human lactate dehydrogenase a inhibitors: a molecular dynamics investigation. PloS one, 9(1), e86365.

https://doi.org/10.1371/journal.pone.0086365
17) Sousa, A. P., Cunha, D. M., Franco, C., Teixeira, C., Gojon, F., Baylina, P., & Fernandes, R. (2021). Which Role Plays 2-Hydroxybutyric Acid on Insulin Resistance?. Metabolites, 11(12), 835. https://doi.org/10.3390/metabo11120835
18) Valvona, C. J., Fillmore, H. L., Nunn, P. B., & Pilkington, G. J. (2016). The Regulation and Function of Lactate Dehydrogenase A: Therapeutic Potential in Brain Tumor. Brain pathology (Zurich, Switzerland), 26(1), 3–17. https://doi.org/10.1111/bpa.12299.