Le Chatelier’s principle and metabolism: Biothermodynamic analysis of the metabolic pathway for synthesis of glucagon
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Abstract
Glucagon is the main catabolic hormone in the human organism. Glucagon has been well studied from the aspect of life and biomedical sciences. However, no analysis of glucagon based on chemical thermodynamics can be found in the literature. The approach of biothermodynamics would allow to study the driving force of glucagon production, as well as provide an understanding of the process from the aspect of the fundamental laws of nature. This research reports an analysis of glucagon with the methodology of biothermodynamics. Based on the protein sequences, chemical and thermodynamic characterization of glucagon, proglucagon, preproglucagon and related peptides is performed, with the atom counting method and Patel-Erickson-Battley model. Reactions of translation at the ribosomes and post-translational processing are formulated and their driving force (Gibbs energy change) is calculated. The process of translation at the ribosomes that produces preproglucagon is studied from the aspect of chemical thermodynamics. Based on Gibbs energy, an analysis is performed of the metabolic pathway for production of glucagon. The role of Le Chatelier’s principle in coupling of the reactions in the metabolic pathway is studied. Finally, a discussion is made of applications of the biothermodynamic methodology in omics research for determination of feasibility of metabolic pathways.
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This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution license 4.0 that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
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Ministarstvo Prosvete, Nauke i Tehnološkog Razvoja
Grant numbers 451-03-136/2025-03/200026
References
J. Philippe, The Glucagon Gene and Its Expression, in: Glucagon III. Handbook of Experimental Pharmacology, vol 123, P.J. Lefèbvre, Ed., Springer, Berlin, Germany, 1996 (https://doi.org/10.1007/978-3-642-61150-6_2)
Bataille, D.. Preproglucagon and Its Processing. In: Glucagon III. Handbook of Experimental Pharmacology, vol 123, P.J. Lefèbvre, Ed., Springer, Berlin, Germany, 1996 (https://doi.org/10.1007/978-3-642-61150-6_3)
S. Lang, D. Nguyen, P. Bhadra, M. Jung, V. Helms, R. Zimmermann, Front. Physiol. 13 (2022) 833540 (https://doi.org/10.3389/fphys.2022.833540)
K. Ono, Int. J. Mol. Sci. 25 (2024) 13534 (https://doi.org/10.3390/ijms252413534)
P. Lindquist, J. S. Madsen, H. Bräuner-Osborne, M. M. Rosenkilde, A. S. Hauser, Front. Endocrin. 12 (2021) 698511 (https://doi.org/10.3389/fendo.2021.698511)
R. C. Moffett, N. G. Docherty, C. W. le Roux, Appetite 156 (2021) 104807 (https://doi.org/10.1016/j.appet.2020.104807)
R. D. Wideman, S. D. Covey, G. C. Webb, D. J. Drucker, T. J. Kieffer, Diabetes 56 (2007) 2744–2752 (https://doi.org/10.2337/db07-0563)
I. Rix, C. Nexøe-Larsen, N.C. Bergmann et al., Glucagon Physiology, in: Endotext, K.R. Feingold, S.F. Ahmed, B. Anawalt et al., Eds., MDText.com Inc., South Dartmouth, MA, USA, 2019. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279127/
UniProt: P01275 · GLUC_HUMAN, Available at: https://www.uniprot.org/uniprotkb/P01275/entry (Accessed on August 9, 2025)
PubChem: Compound summary: Glucagon, Available at: https://pubchem.ncbi.nlm.nih.gov/compound/Glucagon (Accessed on August 9, 2025)
NCBI: Pro-glucagon preproprotein (Homo sapiens), Available at: https://www.ncbi.nlm.nih.gov/protein/NP_002045.1?report=genbank&log$=protalign&blast_rank=6&RID=7J5YEGKW014 (Accessed on August 9, 2025)
J. Thomsen, K. Kristiansen, K. Brunfeldt, F. Sundby, FEBS Lett. 21 (1972) 315–319 (https://doi.org/10.1016/0014-5793(72)80192-3)
R. A. Alberty, R. N. Goldberg, Biochemistry 31 (1992) 10610–10615 (https://doi.org/10.1021/bi00158a025)
P. W. Atkins, J. de Paula,. Physical Chemistry for the Life Sciences (2nd edition), W. H. Freeman and Company, New York, USA, 2011. ISBN-13: 978-1429231145
S. Perisanu, D. Gheorghe, A. Neacsu, Ins. Chem. Biochem. 1 (2020) 1 (https://doi.org/10.33552/ICBC.2020.01.000515)
V. Pokorný, V. Štejfa, J. Havlín, M. Fulem, K. Růžička, Molecules 29 (2024) 5366 (https://doi.org/10.3390/molecules29225366)
V. Pokorný, V. Štejfa, J. Havlín, M. Fulem, K. Růžička, Molecules 28 (2023) 451 (https://doi.org/10.3390/molecules28010451)
V. Pokorný, E. Lieberzeitová, V. Štejfa J. Havlín, M. Fulem, K. Růžička, Int. J. Thermophys. 42 (2021) 160 (https://doi.org/10.1007/s10765-021-02911-z)
V. Pokorný, V. Štejfa, J. Havlín, K. Růžička, M. Fulem, Molecules 26 (2021) 4298 (https://doi.org/10.3390/molecules26144298)
V. Pokorný, C. Červinka, V. Štejfa, J. Havlín, K. Růžička, M. Fulem, J. Chem. Eng. Data 65 (2020) 1833-1849 (https://doi.org/10.1021/acs.jced.9b01086)
P. Vieillard, Y. Tardy, Thermochemical Properties of Phosphates, in: Phosphate Minerals, J.O. Nriagu, P.B. Moore, Eds., Springer, Berlin, Germany, 1984. https://doi.org/10.1007/978-3-642-61736-2_4
M. Popovic, Comp. Biol. Chem. 96 (2022) 107621 (https://doi.org/10.1016/j.compbiolchem.2022.107621)
M. Popovic, V. Tadić, M. Mihailović, J. Biomol. Struct. Dyn. 42 (2024) 10388–10400 (https://doi.org/10.1080/07391102.2023.2256880)
M. E. Popović, M. Stevanović, M. Pantović Pavlović, J. Mol. Evol. 92 (2024) 776–798 (https://doi.org/10.1007/s00239-024-10205-9)
E. H. Battley, Thermochim. Acta 309 (1998) 17-37 (https://doi.org/10.1016/S0040-6031(97)00357-2)
E. H. Battley, Thermochim. Acta 326 (1999) 7-15 (https://doi.org/10.1016/S0040-6031(98)00584-X)
S. A. Patel, L. E. Erickson, Biotechnol. Bioeng. 23 (1981) 2051-2067 (https://doi.org/10.1002/bit.260230910)
E. H. Battley, J. R. Stone, Thermochim. Acta 349 (2000) 153-161 (https://doi.org/10.1016/S0040-6031(99)00509-2)
P. W. Atkins, J. de Paula, Physical Chemistry: Thermodynamics, Structure, and Change, 10th Edition. W. H. Freeman and Company, New York, USA, 2014. ISBN-13: 978-1429290197
J. E. Hurst, B. K. Harrison, Chem. Eng. Comm. 112 (1992) 21-30 (https://doi.org/10.1080/00986449208935989)
M. Ozilgen, E. Sorguven Oner, Biothermodynamics: Principles and Applications (1st ed.), CRC Press, Boca Raton, Florida, USA, 2016 (https://doi.org/10.1201/9781315374147)
J. Stenesh, Translation—The Synthesis of Protein, in: Biochemistry, Springer, Boston, MA; USA, 1998 (https://doi.org/10.1007/978-1-4757-9427-4_19)
B. Alberts, A. Johnson, J. Lewis et al., From RNA to Protein, in: Molecular Biology of the Cell. 4th edition, Garland Science, New York, USA, 2002. Available from: https://www.ncbi.nlm.nih.gov/books/NBK26829/
J. M. Berg, J. L. Tymoczko, L. Stryer, Biochemistry, 5th ed., Freeman, New York, USA, 2002. ISBN-13: 978-0716746843
M. E. Popović, M. Popović, D. Pei, Biophysica 5 (2025) 19 (https://doi.org/10.3390/biophysica5020019)
U. Von Stockar. Live cells as open non-equilibrium systems. In Biothermodynamics: The Role of Thermodynamics in Biochemical Engineering, , (Eds.: U. von Stockar, L. A. M. van der Wielen), EPFL Press, Lausanne, Switzerland, (2013) pp. 399-421 (https://doi.org/10.1201/b15428)
T. Cossetto, J. Rodenfels, P. Sartori, Nat. Comm. 16 (2025) 8543 (https://doi.org/10.1038/s41467-025-62975-5)
S. Calabrese, A. Chakrawal, S. Manzoni, P. Van Cappellen, PNAS 118 (2021) e2107668118 (https://doi.org/10.1073/pnas.2107668118)
V. Piñeiro, Y. Lestido-Cardama, C. Pérez-Cruzado, N. Barros, Soil Biol. Biochem. 206 (2025) 109812 (https://doi.org/10.1016/j.soilbio.2025.109812)
U. Lucia, G. Grisolia, Inventions 10 (2025) 47 (https://doi.org/10.3390/inventions10040047)
M. E. Popović, M. Stevanović, V. Tadić, Virology 614 (2025) 110742 (https://doi.org/10.1016/j.virol.2025.110742)
M. E. Popović, M. Stevanović, M. P. Pavlović, Microbial Risk Analysis 26 (2024) 100292 (https://doi.org/10.1016/j.mran.2024.100292)
M. Özilgen, B. Yilmaz, Int. J. Energy Res. 45 (2021) 1157–1160 (https://doi.org/10.1002/er.5883)
M. E. Popović, Zoology 163 (2024) 126158 (https://doi.org/10.1016/j.zool.2024.126158)
V. Dragičević, Thermodynamics of Abiotic Stress and Stress Tolerance of Cultivated Plants, In: Recent Advances in Thermo and Fluid Dynamics, M. Gorji-Bandpy, ed., InTech, Rijeka, Croatia, 2015 (https://doi.org/10.5772/60990)
O. Ebenhöh, J. Ebeling, R. Meyer, F. Pohlkotte, T. Nies, Life 14 (2024) 247 (https://doi.org/10.3390/life14020247)
M. Corrao, H. He, W. Liebermeister, E. Noor, A. Bar-Even, PLoS Comp. Bio. 21 (2025) e1013564 (https://doi.org/10.1371/journal.pcbi.1013564)
Y. Demirel, Nonequilibrium Thermodynamics: Transport and Rate Processes in Physical, Chemical and Biological Systems, 3rd ed., Elsevier, Amsterdam, Netherlands, 2014. ISBN: 9780444595812
O. Shpielberg, E. Akkermans, Phys. Rev. Lett. 116 (2016) 240603 (https://doi.org/10.1103/PhysRevLett.116.240603)
A. E. Allahverdyan, A. Galstyan, Physical Review E 84 (2011) 041117 (https://doi.org/10.1103/PhysRevE.84.041117)
R. T. Balmer, Modern Engineering Thermodynamics, Academic Press, Cambridge, MA, USA, 2010 (https://doi.org/10.1016/C2009-0-20199-1)
M.E. Popović, V. Tadić, M. Popović, Virology 603 (2025) 110319 (https://doi.org/10.1016/j.virol.2024.110319)
U. von Stockar, J. Liu, Biochim. Biophys Acta 1412 (1999) 191–211 (https://doi.org/10.1016/s0005-2728(99)00065-1)
S. I. Sandler, H. Orbey, Biotech. Bioeng. 38 (1991) 697–718 (https://doi.org/10.1002/bit.260380704)
U. von Stockar, Biothermodynamics of live cells: energy dissipation and heat generation in cellular structures. In: Biothermodynamics: The Role of Thermodynamics in Biochemical Engineering, (Eds.: U. von Stockar, L. A. M. van der Wielen), EPFL Press, Lausanne, Switzerland, (2013) pp. 475-534 (https://doi.org/10.1201/b15428)
M. Popovic, G. B. G. Stenning, A. Göttlein, M. Miniceva, J. Biotech. 331 (2021) 99-107 (https://doi.org/10.1016/j.jbiotec.2021.03.006)
M. Popovic, Helyon 5 (2019) e01950 (https://doi.org/10.1016/j.heliyon.2019.e01950)
N. Barros, M. Popovic, J. Molina-Valero, Y. Lestido-Cardama, C. Pérez-Cruzado, Sci. Rep. 14 (2024) 16644 (https://doi.org/10.1038/s41598-024-67590-w)
B. Şimşek, M. Özilgen, F. Ş. Utku, Energy Storage 4 (2022) e298 (https://doi.org/10.1002/est2.298).