LACTIC ACID AS A SYSTEMIC PRODUCT AND BIOMARKER OF PHYSICAL LOAD
DOI: http://dx.doi.org/10.30970/sbi.1701.703
Abstract
This paper presents an up-to-date review of research data on the specific features of lactic acid metabolism and its role as an effector of vital regulatory mechanisms. Lactic acid is an alpha-hydroxy monocarboxylic acid. Physical loads of submaximal intensity and some diseases can cause dramatic increase of lactic acid content in the body fluids. The excessive lactate is removed from the working muscle and either metabolized by other tissues or excreted from the human body. Alteration of the lactate-pyruvate balance is one of the main markers of the development of cardiac hypertrophy and failure. The redistribution of lactate between the cells producing it and the cells that metabolize it is vital to maintain a stable pH level in tissues and hold lactate in the body since this compound is an important energy source as well as an effector of important regulatory mechanisms. The quantification of lactate is used to assess general physical capabilities of the human body, the intensity of physical load and the rate of recovery in physical rehabilitation.
Specialized proteins, which refer to the group of monocarboxylate transporters, are involved in lactate excretion and absorption by cells. The presence of various types of transporters in cell membranes that differ in affinity to lactate and the direction of transport ensures a rapid redistribution of lactic acid throughout the body and regulates the intensity and direction of its metabolism according to the physiological needs.
Efficient transfer and redistribution of lactate between different tissues of the body is essential, given the participation of lactate in several important regulatory mechanisms.
As an effector, lactate is involved in the regulation of angiogenesis, differentiation of myosatellitocytes, regeneration of muscle fibers, polarization of macrophages and the course of inflammatory processes. Besides, lactate participates in epigenetic mechanisms of muscle tissue metabolism regulation. Therefore, lactate is one of the key metabolites in the human body.
Keywords
Full Text:
PDF (Українська)References
Bendahan, D., Chatel, B., & Jue, T. (2017). Comparative NMR and NIRS analysis of oxygen-dependent metabolism in exercising finger flexor muscles. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 313(6), R740-R753. doi:10.1152/ajpregu.00203.2017 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
Bergersen, L. H. (2015). Lactate transport and signaling in the brain: potential therapeutic targets and roles in body-brain Interaction. Journal of Cerebral Blood Flow & Metabolism, 35(2), 176-185. doi:10.1038/jcbfm.2014.206 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
Bisetto, S., Wright, M. C., Nowak, R. A., Lepore, A. C., Khurana, T. S., Loro, E., & Philp, N. J. (2019). New insights into the lactate shuttle: role of MCT4 in the modulation of the exercise capacity. iScience, 22, 507-518. doi:10.1016/j.isci.2019.11.041 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
Bonen, A., Heynen, M., & Hatta, H. (2006). Distribution of monocarboxylate transporters MCT1-MCT8 in rat tissues and human skeletal muscle. Applied Physiology, Nutrition, and Metabolism, 31(1), 31-39. doi:10.1139/h05-002 Crossref ● PubMed ● Google Scholar | ||||
| ||||
Bosshart, P. D., Charles, R.-P., Garibsingh, R.-A. A., Schlessinger, A., & Fotiadis, D. (2021). SLC16 family: from atomic structure to human disease. Trends in Biochemical Sciences, 46(1), 28-40. doi:10.1016/j.tibs.2020.07.005 Crossref ● PubMed ● Google Scholar | ||||
| ||||
Bricker, D. K., Taylor, E. B., Schell, J. C., Orsak, T., Boutron, A., Chen, Y.-C., Cox, J. E., Cardon, C. M., Van Vranken, J. G., Dephoure, N., Redin, C., Boudina, S., Gygi, S. P., Brivet, M., Thummel, C. S., & Rutter, J. (2012). A mitochondrial pyruvate carrier required for pyruvate uptake in yeast, Drosophila, and humans. Science, 337(6090), 96-100. doi:10.1126/science.1218099 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
Brooks, G. A. (2020). Lactate as a fulcrum of metabolism. Redox Biology, 35, 101454. doi:10.1016/j.redox.2020.101454 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
Cluntun, A. A., Badolia, R., Lettlova, S., Parnell, K. M., Shankar, T. S., Diakos, N. A., … & Drakos, S. G. (2021). The pyruvate-lactate axis modulates cardiac hypertrophy and heart failure. Cell Metabolism, 33(3), 629-648.e10. doi:10.1016/j.cmet.2020.12.003 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
Costa Leite, T., Da Silva, D., Guimarães Coelho, R., Zancan, P., & Sola-Penna, M. (2007). Lactate favours the dissociation of skeletal muscle 6-phosphofructo-1-kinase tetramers down-regulating the enzyme and muscle glycolysis. Biochemical Journal, 408(1), 123-130. doi:10.1042/bj20070687 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
Dimmer, K. S., Friedrich, B., Lang, F., Deitmer, J. W., & Bröer, S. (2000). The low-affinity monocarboxylate transporter MCT4 is adapted to the export of lactate in highly glycolytic cells. Biochemical Journal, 350(1), 219-227. doi:10.1042/bj3500219 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
Divakaruni, A. S., & Murphy, A. N. (2012). A mitochondrial mystery, solved. Science, 337(6090), 41-43. doi:10.1126/science.1225601 Crossref ● PubMed ● Google Scholar | ||||
| ||||
Fedotovskaya, O. N., Mustafina, L. J., Popov, D. V., Vinogradova, O. L., & Ahmetov, I. I. (2014). A common polymorphism of the MCT1 gene and athletic performance. International Journal of Sports Physiology and Performance, 9(1), 173-180. doi:10.1123/ijspp.2013-0026 Crossref ● PubMed ● Google Scholar | ||||
| ||||
Felmlee, M. A., Jones, R. S., Rodriguez-Cruz, V., Follman, K. E., & Morris, M. E. (2020). Monocarboxylate transporters (SLC16): function, regulation, and role in health and disease. Pharmacological Reviews, 72(2), 466-485. doi:10.1124/pr.119.018762 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
Fernández-Ruiz, I. (2021). Rebalancing the pyruvate-lactate axis to treat heart failure. Nature Reviews Cardiology, 18(3), 150-151. doi:10.1038/s41569-021-00513-8 Crossref ● Google Scholar | ||||
| ||||
Fishbein, W. N., Merezhinskaya, N., & Foellmer, J. W. (2002). Relative distribution of three major lactate transporters in frozen human tissues and their localization in unfixed skeletal muscle. Muscle & Nerve, 26(1), 101-112. doi:10.1002/mus.10168 Crossref ● PubMed ● Google Scholar | ||||
| ||||
Flores, A., Schell, J., Krall, A. S., Jelinek, D., Miranda, M., Grigorian, M., Braas, D., White, A. C., Zhou, J. L., Graham, N. A., Graeber, T., Seth, P., Evseenko, D., Coller, H. A., Rutter, J., Christofk, H. R., & Lowry, W. E. (2017). Lactate dehydrogenase activity drives hair follicle stem cell activation. Nature Cell Biology, 19(9), 1017-1026. doi:10.1038/ncb3575 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
Franco-Martínez, L., Tvarijonaviciute, A., Martínez-Subiela, S., Márquez, G., Martínez Díaz, N., Cugat, R., Cerón, J. J., & Jiménez-Reyes, P. (2019). Changes in lactate, ferritin, and uric acid in saliva after repeated explosive effort sequences. The Journal of Sports Medicine and Physical Fitness, 59(6). doi:10.23736/s0022-4707.18.08792-3 Crossref ● PubMed ● Google Scholar | ||||
| ||||
Gladden, L. B. (2004). Lactate metabolism: a new paradigm for the third millennium. The Journal of Physiology, 558(1), 5-30. doi:10.1113/jphysiol.2003.058701 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
Gray, L. R., Sultana, M. R., Rauckhorst, A. J., Oonthonpan, L., Tompkins, S. C., Sharma, A., ... & Taylor, E. B. (2015). Hepatic mitochondrial pyruvate carrier 1 is required for efficient regulation of gluconeogenesis and whole-body glucose homeostasis. Cell Metabolism, 22(4), 669-681. doi:10.1016/j.cmet.2015.07.027 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
Haas, S. A., Lange, T., Saugel, B., Petzoldt, M., Fuhrmann, V., Metschke, M., & Kluge, S. (2015). Severe hyperlactatemia, lactate clearance and mortality in unselected critically ill patients. Intensive Care Medicine, 42(2), 202-210. doi:10.1007/s00134-015-4127-0 Crossref ● PubMed ● Google Scholar | ||||
| ||||
Halestrap, A. P. (2011). The monocarboxylate transporter family - structure and functional characterization. IUBMB Life, 64(1), 1-9. doi:10.1002/iub.573 Crossref ● PubMed ● Google Scholar | ||||
| ||||
Halestrap, A. P. (2013). Monocarboxylic acid transport. Comprehensive Physiology, 3(4), 1611-1643. doi:10.1002/cphy.c130008 Crossref ● PubMed ● Google Scholar | ||||
| ||||
Halestrap, A. P., & Wilson, M. C. (2011). The monocarboxylate transporter family - role and regulation. IUBMB Life, 64(2), 109-119. doi:10.1002/iub.572 Crossref ● PubMed ● Google Scholar | ||||
| ||||
Hargreaves, M., & Spriet, L. L. (2020). Skeletal muscle energy metabolism during exercise. Nature Metabolism, 2(9), 817-828. doi:10.1038/s42255-020-0251-4 Crossref ● PubMed ● Google Scholar | ||||
| ||||
Hashchyshyn, V., Tymochko-Voloshyn, R., Paraniak, N., Vovkanych, L., Hlozhyk, I., Trach, V., Muzyka, F., Serafyn, Y., Prystupa, E., & Boretsky, Y. (2022). Regeneration of skeletal muscle fibers and regulation of myosatellitocytes metabolism. Cytology and Genetics, 56(3), 253-260. doi:10.3103/s0095452722030033 Crossref ● Google Scholar | ||||
| ||||
Hertz, L., & Dienel, G. A. (2004). Lactate transport and transporters: general principles and functional roles in brain cells. Journal of Neuroscience Research, 79(1-2), 11-18. doi:10.1002/jnr.20294 Crossref ● PubMed ● Google Scholar | ||||
| ||||
Iacono, K. T., Brown, A. L., Greene, M. I., & Saouaf, S. J. (2007). CD147 immunoglobulin superfamily receptor function and role in pathology. Experimental and Molecular Pathology, 83(3), 283-295. doi:10.1016/j.yexmp.2007.08.014 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
Kang, K. P., Lee, S., & Kang, S. K. (2006). D-lactic acidosis in humans: review of update. Electrolyte & Blood Pressure, 4(1), 53-56. doi:10.5049/ebp.2006.4.1.53 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
Kirk, P., Wilson, M. C., Heddle, C., Brown, M. H., Barclay, A. N., & Halestrap, A. P. (2000). CD147 is tightly associated with lactate transporters MCT1 and MCT4 and facilitates their cell surface expression. The EMBO Journal, 19(15), 3896-3904. doi:10.1093/emboj/19.15.3896 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
Levy, B. (2006). Lactate and shock state: the metabolic view. Current Opinion in Critical Care, 12(4), 315-321. doi:10.1097/01.ccx.0000235208.77450.15 Crossref ● PubMed ● Google Scholar | ||||
| ||||
Li, X., Yang, Y., Zhang, B., Lin, X., Fu, X., An, Y., Zou, Y., Wang, J.-X., Wang, Z., & Yu, T. (2022). Lactate metabolism in human health and disease. Signal Transduction and Targeted Therapy, 7(1), 305. doi:10.1038/s41392-022-01151-3 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
Manning Fox, J. E., Meredith, D., & Halestrap, A. P. (2000). Characterisation of human monocarboxylate transporter 4 substantiates its role in lactic acid efflux from skeletal muscle. The Journal of Physiology, 529(2), 285-293. doi:10.1111/j.1469-7793.2000.00285.x Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
Martín, A., Kim, J., Kurniawan, J. F., Sempionatto, J. R., Moreto, J. R., Tang, G., Campbell, A. S., Shin, A., Lee, M. Y., Liu, X., & Wang, J. (2017). Epidermal microfluidic electrochemical detection system: enhanced sweat sampling and metabolite detection. ACS Sensors, 2(12), 1860-1868. doi:10.1021/acssensors.7b00729 Crossref ● PubMed ● Google Scholar | ||||
| ||||
Matsui, T., Omuro, H., Liu, Y.-F., Soya, M., Shima, T., McEwen, B. S., & Soya, H. (2017). Astrocytic glycogen-derived lactate fuels the brain during exhaustive exercise to maintain endurance capacity. Proceedings of the National Academy of Sciences, 114(24), 6358-6363. doi:10.1073/pnas.1702739114 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
McCommis, K. S., & Finck, B. N. (2015). Mitochondrial pyruvate transport: a historical perspective and future research directions. Biochemical Journal, 466(3), 443-454. doi:10.1042/bj20141171 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
Merezhinskaya, N., Fishbein, W. N., Davis, J. I., & Foellmer, J. W. (2000). Mutations in MCT1 cDNA in patients with symptomatic deficiency in lactate transport. Muscle & Nerve, 23(1), 90-97. doi:10.1002/(SICI)1097-4598(200001)23:1<90::AID-MUS12>3.0.CO;2-M Crossref ● PubMed ● Google Scholar | ||||
| ||||
Merezhinskaya, N., & Fishbein, W. N. (2009). Monocarboxylate transporters: past, present, and future. Histology and Histopathology, 24(2), 243-264. doi:10.14670/HH-24.243 Crossref ● PubMed ● Google Scholar | ||||
| ||||
Mintun, M. A., Vlassenko, A. G., Rundle, M. M., & Raichle, M. E. (2004). Increased lactate/pyruvate ratio augments blood flow in physiologically activated human brain. Proceedings of the National Academy of Sciences, 101(2), 659-664. doi:10.1073/pnas.0307457100 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
Nagampalli, R. S. K., Quesñay, J. E. N., Adamoski, D., Islam, Z., Birch, J., Sebinelli, H. G., ... & Ambrosio, A. L. B. (2018). Human mitochondrial pyruvate carrier 2 as an autonomous membrane transporter. Scientific Reports, 8(1). doi:10.1038/s41598-018-21740-z Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
Nalbandian, M., Radak, Z., & Takeda, M. (2019). N-acetyl-L-cysteine prevents lactate-mediated PGC1-alpha expression in C2C12 myotubes. Biology, 8(2), 44. doi:10.3390/biology8020044 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
Noor, S. I., Jamali, S., Ames, S., Langer, S., Deitmer, J. W., & Becker, H. M. (2018). A surface proton antenna in carbonic anhydrase II supports lactate transport in cancer cells. eLife, 7, e35176. doi:10.7554/elife.35176 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
Okano, S., Nishizawa, H., Yui, J., & Nakamura, A. (2022). Impact of body fat, body water content, and skeletal muscle mass index on peak salivary lactate levels after squat jump exercise in healthy non-athlete adult males. BMC Sports Science, Medicine and Rehabilitation, 14(1), 91. doi:10.1186/s13102-022-00482-6 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
Okorie, O. N., & Dellinger, P. (2011). Lactate: biomarker and potential therapeutic target. Critical Care Clinics, 27(2), 299-326. doi:10.1016/j.ccc.2010.12.013 Crossref ● PubMed ● Google Scholar | ||||
| ||||
Payen, V. L., Mina, E., Van Hée, V. F., Porporato, P. E., & Sonveaux, P. (2020). Monocarboxylate transporters in cancer. Molecular Metabolism, 33, 48-66. doi:10.1016/j.molmet.2019.07.006 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
Poole, R. C., & Halestrap, A. P. (1994). N-terminal protein sequence analysis of the rabbit erythrocyte lactate transporter suggests identity with the cloned monocarboxylate transport protein MCT1. Biochemical Journal, 303(3), 755-759. doi:10.1042/bj3030755 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
Poole, R. C., Sansom, C. E., & Halestrap, A. P. (1996). Studies of the membrane topology of the rat erythrocyte H+/lactate cotransporter (MCT1). Biochemical Journal, 320(3), 817-824. doi:10.1042/bj3200817 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
Quesñay, J. E. N., Pollock, N. L., Nagampalli, R. S. K., Lee, S. C., Balakrishnan, V., Dias, S. M. G., Moraes, I., Dafforn, T. R., & Ambrosio, A. L. B. (2020). Insights on the quest for the structure-function relationship of the mitochondrial pyruvate carrier. Biology, 9(11), 407. doi:10.3390/biology9110407 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
Ramírez de la Piscina-Viúdez, X., Álvarez-Herms, J., Bonilla, D. A., Castañeda-Babarro, A., Larruskain, J., Díaz-Ramírez, J., Ahmetov, I. I., Martínez-Ascensión, A., Kreider, R. B., & Odriozola-Martínez, A. (2021). Putative role of MCT1 rs1049434 polymorphism in high-intensity endurance performance: concept and basis to understand possible individualization stimulus. Sports, 9(10), 143. doi:10.3390/sports9100143 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
Ren, T., Jones, R. S., & Morris, M. E. (2022). Untargeted metabolomics identifies the potential role of monocarboxylate transporter 6 (MCT6/SLC16A5) in lipid and amino acid metabolism pathways. Pharmacology Research & Perspectives, 10(3), e00944. doi:10.1002/prp2.944 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
Sheeran, F. L., Angerosa, J., Liaw, N. Y., Cheung, M. M., & Pepe, S. (2019). Adaptations in protein expression and regulated activity of pyruvate dehydrogenase multienzyme complex in human systolic heart failure. Oxidative Medicine and Cellular Longevity, 2019, 1-11. doi:10.1155/2019/4532592 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
Smutok, O., Gayda, G., Gonchar, M., & Schuhmann, W. (2005). A novel L-lactate-selective biosensor based on flavocytochrome b2 from methylotrophic yeast Hansenula polymorpha. Biosensors and Bioelectronics, 20(7), 1285-1290. doi:10.1016/j.bios.2004.04.020 Crossref ● PubMed ● Google Scholar | ||||
| ||||
Takahashi, S. (2022). Metabolic contribution and cerebral blood flow regulation by astrocytes in the neurovascular unit. Cells, 11(5), 813. doi:10.3390/cells11050813 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
Wang, L., Xu, M., Qin, J., Lin, S.-C., Lee, H.-J., Tsai, S. Y., & Tsai, M.-J. (2016). MPC1, a key gene in cancer metabolism, is regulated by COUPTFII in human prostate cancer. Oncotarget, 7(12), 14673-14683. doi:10.18632/oncotarget.7405 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
Wang, N., Jiang, X., Zhang, S., Zhu, A., Yuan, Y., Xu, H., Lei, J., & Yan, C. (2021). Structural basis of human monocarboxylate transporter 1 inhibition by anti-cancer drug candidates. Cell, 184(2), 370-383.e13. doi:10.1016/j.cell.2020.11.043 Crossref ● PubMed ● Google Scholar | ||||
| ||||
Wilson, M. C., Meredith, D., Fox, J. E. M., Manoharan, C., Davies, A. J., & Halestrap, A. P. (2005). Basigin (CD147) is the target for organomercurial inhibition of monocarboxylate transporter isoforms 1 and 4: the ancillary protein for the insensitive MCT2 is embigin (gp70). Journal of Biological Chemistry, 280(29), 27213-27221. doi:10.1074/jbc.m411950200 Crossref ● PubMed ● Google Scholar | ||||
| ||||
Zhang, J., Muri, J., Fitzgerald, G., Gorski, T., Gianni-Barrera, R., Masschelein, E., ... & De Bock, K. (2020). Endothelial lactate controls muscle regeneration from ischemia by inducing M2-like macrophage polarization. Cell Metabolism, 31(6), 1136-1153.e7. doi:10.1016/j.cmet.2020.05.004 Crossref ● PubMed ● PMC ● Google Scholar |
Refbacks
- There are currently no refbacks.
Copyright (c) 2023 Yu. R. Boretsky, I. Z. Hlozhyk, V. R. Hashchyshyn, R. I. Tymochko-Voloshyn, N. M. Paraniak, K. E. Shavel, M. V. Stefanyshyn, I. V. Verbin, V. F. Ivashchenko, G. Z. Gayda, M. V. Gonchar
This work is licensed under a Creative Commons Attribution 4.0 International License.