Home Life Sciences Mathematical expressions describing enzyme velocity and inhibition at high enzyme concentration
Article
Licensed
Unlicensed Requires Authentication

Mathematical expressions describing enzyme velocity and inhibition at high enzyme concentration

  • Agustín Hernández ORCID logo EMAIL logo
Published/Copyright: September 26, 2022

Abstract

Enzyme behaviour is characterised in the laboratory using diluted solutions of enzyme. However, in vivo processes usually occur at [S T ] ≈ [E T ] ≈ K m . Furthermore, the study of enzyme action involves characterisation of inhibitors and their mechanisms. However, to date, there have been no reports proposing mathematical expressions that can be used to describe enzyme activity at high enzyme concentration apart from the simplest single substrate, irreversible case. Using a continued fraction approach, equations can be easily derived for the most common cases in monosubstrate reactions, such as irreversible or reversible reactions and effector (inhibitor or activator) kinetic interactions. These expressions are an extension of the classical Michaelis-Menten equations. A first analysis using these expressions permits to deduce some differences at high versus low enzyme concentration, such as the greater effectiveness of allosteric inhibitors compared to catalytic ones. Also, they can be used to understand catalyst saturation in a reaction. Although they can be linearised, these equations also show differences that need to be taken into account. For example, the different meaning of line intersection points in Dixon plots. All in all, these expressions may be useful tools for modelling in vivo and biotechnological processes.


Corresponding author: Agustín Hernández, Unit for Integrated Research on Tropical Biodiversity – BIOTROP, Centre for Biological and Health Sciences, Federal University of Sao Carlos, Sao Carlos (SP), Brazil, E-mail:

Acknowledgements

The author thanks Ms E. A. de Magalhaes, and Dr L. Pino (CNR-ITAE “Nicola Giordano”), for their help in this study, and to late Drs D. T. Cooke and D. T. Clarkson (IACR-Long Ashton Res. Stn) for lifelong teaching through example.

  1. Author contributions: The author has accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

  3. Conflict of interest statement: The author declares to have no conflicts of interest regarding this manuscript.

  4. Compliance with ethical norms: This article does not contain descriptions of studies performed by the authors with participation of humans or using animals as objects.

References

Acerenza, L. and Kacser, H. (1990). Enzyme kinetics and metabolic control. A method to test and quantify the effect of enzymic properties on metabolic variables. Biochem. J. 269: 697–707, https://doi.org/10.1042/bj2690697.Search in Google Scholar PubMed PubMed Central

Bajzer, Z. and Strehler, E.E. (2012). About and beyond the Henri-Michaelis-Menten rate equation for single-substrate enzyme kinetics. Biochem. Biophys. Res. Commun. 417: 982–985, https://doi.org/10.1016/j.bbrc.2011.12.051.Search in Google Scholar PubMed

Baykov, A.A. and Avaeva, S.M. (1974). Yeast inorganic pyrophosphatase: studies on metal binding. Eur. J. Biochem. 47: 57–66, https://doi.org/10.1111/j.1432-1033.1974.tb03667.x.Search in Google Scholar PubMed

Borghans, J.A., de Boer, R.J., and Segel, L.A. (1996). Extending the quasi-steady state approximation by changing variables. Bull. Math. Biol. 58: 43–63, https://doi.org/10.1007/bf02458281.Search in Google Scholar

Briggs, G.E. and Haldane, J.B.S. (1925). A note on the kinetics of enzyme action. Biochem. J. 19: 338–339, https://doi.org/10.1042/bj0190338.Search in Google Scholar PubMed PubMed Central

Cha, S. and Cha, C.-J.M. (1965). Kinetics of cyclic enzyme systems. Mol. Pharmacol. 1: 178–189.Search in Google Scholar

Cornish-Bowden, A. (1974). A simple graphical method for determining the inhibition constants of mixed, uncompetitive and non-competitive inhibitors. Biochem. J. 137: 143–144, https://doi.org/10.1042/bj1370143.Search in Google Scholar PubMed PubMed Central

Goudar, C.T., Harris, S.K., McInerney, M.J., and Suflita, J.M. (2004). Progress curve analysis for enzyme and microbial kinetic reactions using explicit solutions based on the Lambert W function. J. Microbiol. Methods 59: 317–326, https://doi.org/10.1016/j.mimet.2004.06.013.Search in Google Scholar PubMed

Hayden, T.L. (1965). Continued fraction approximation to functions. Numer. Math. 7: 292–309, https://doi.org/10.1007/bf01436523.Search in Google Scholar

Heinonen, J.K. (2001). Biological role of inorganic pyrophosphate. Kluwer Academic Publishers, Dordrecht.10.1007/978-1-4615-1433-6Search in Google Scholar

Ho, B., Baryshnikova, A., and Brown, G.W. (2018). Unification of protein abundance datasets yields a quantitative Saccharomyces cerevisiae proteome. Cell Syst. 6: 192–205.e3, https://doi.org/10.1016/j.cels.2017.12.004.Search in Google Scholar PubMed

Kargi, F. (2009). Generalized rate equation for single-substrate enzyme catalyzed reactions. Biochem. Biophys. Res. Commun. 382: 157–159, https://doi.org/10.1016/j.bbrc.2009.02.155.Search in Google Scholar PubMed

Kari, J., Andersen, M., Borch, K., and Westh, P. (2017). An inverse Michaelis–Menten approach for interfacial enzyme kinetics. ACS Catal. 7: 4904–4914, https://doi.org/10.1021/acscatal.7b00838.Search in Google Scholar

Knight, Z.A. and Shokat, K.M. (2005). Features of selective kinase inhibitors. Chem. Biol. 12: 621–637, https://doi.org/10.1016/j.chembiol.2005.04.011.Search in Google Scholar PubMed

Kukko, E. and Heinonen, J. (1982). The intracellular concentration of pyrophosphate in the batch culture of Escherichia coli. Eur. J. Biochem. 127: 347–349, https://doi.org/10.1111/j.1432-1033.1982.tb06878.x.Search in Google Scholar PubMed

Michaelis, L. and Menten, M.L. (2013). The kinetics of invertin action. 1913. FEBS Lett. 587: 2712–2720, https://doi.org/10.1016/j.febslet.2013.07.015.Search in Google Scholar PubMed

Palma, M., Madeira, S.C., Mendes-Ferreira, A., and Sá-Correia, I. (2012). Impact of assimilable nitrogen availability in glucose uptake kinetics in Saccharomyces cerevisiae during alcoholic fermentation. Microb. Cell Factories 11: 99, https://doi.org/10.1186/1475-2859-11-99.Search in Google Scholar PubMed PubMed Central

Patsatzis, D.G. and Goussis, D.A. (2019). A new Michaelis-Menten equation valid everywhere multi-scale dynamics prevails. Math. Biosci. 315: 108220, https://doi.org/10.1016/j.mbs.2019.108220.Search in Google Scholar PubMed

Pedersen, M.G. and Bersani, A.M. (2010). Introducing total substrates simplifies theoretical analysis at non-negligible enzyme concentrations: pseudo first-order kinetics and the loss of zero-order ultrasensitivity. J. Math. Biol. 60: 267–283, https://doi.org/10.1007/s00285-009-0267-6.Search in Google Scholar PubMed

Pedersen, M.G., Bersani, A.M., Bersani, E., and Cortese, G. (2008). The total quasi-steady-state approximation for complex enzyme reactions. Math. Comput. Simulat. 79: 1010–1019, https://doi.org/10.1016/j.matcom.2008.02.009.Search in Google Scholar

Rosen, D. and Shallit, J. (1978). A continued fraction algorithm for approximating all real polynomial roots. Math. Mag. 51: 112–116, https://doi.org/10.1080/0025570x.1978.11976690.Search in Google Scholar

Schnell, S. and Maini, P.K. (2000). Enzyme kinetics at high enzyme concentration. Bull. Math. Biol. 62: 483–499, https://doi.org/10.1006/bulm.1999.0163.Search in Google Scholar PubMed

Smallbone, K., Messiha, H.L., Carroll, K.M., Winder, C.L., Malys, N., Dunn, W.B., Murabito, E., Swainston, N., Dada, J.O., Khan, F., et al.. (2013). A model of yeast glycolysis based on a consistent kinetic characterisation of all its enzymes. FEBS Lett. 587: 2832–2841, https://doi.org/10.1016/j.febslet.2013.06.043.Search in Google Scholar PubMed PubMed Central


Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/hsz-2022-0163).


Received: 2022-04-19
Accepted: 2022-08-18
Published Online: 2022-09-26
Published in Print: 2023-01-27

© 2022 Walter de Gruyter GmbH, Berlin/Boston

Downloaded on 7.1.2026 from https://www.degruyterbrill.com/document/doi/10.1515/hsz-2022-0163/html
Scroll to top button