Abstract
The Michaelis–Menten–Briggs–Haldane approximation and its extension, the total quasi-steady-state approximation (tQSSA) are famous assumptions for simplification of mathematical modeling of enzyme-substrate reactions. These approximations and their validity conditions are well studied for a single substrate reaction system. However, the extension of these studies for the tQSSA of the general case of multiple substrate reactions is yet to be performed precisely due to the consequent non-linear expressions for tQSSA. In this paper, we introduce a linearization method for equations governing the tQSSA of multiple substrate reactions to obtain an analytical solution for the evolution of concentrations of reactants that is valid throughout the whole time period. In addition, we provide the validity conditions of the tQSSA for multiple substrate reaction systems using the singular perturbation analysis method.
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References
L.A. Segel, M. Slemrod, The quasi-steady-state assumption: a case study in perturbation. SIAM Rev. 31(3), 446–477 (1989)
L. Michaelis, M.L. Menten, Die kinetik der invertinwirkung. Biochem. Z. 49, 333–369 (1913)
G.E. Briggs, J.B.S. Haldane, A note on the kinetics of enzyme action. Biochem. J. 19, 338–339 (1925)
S. Schnell, P.K. Maini, Enzyme kinetics at high enzyme concentration. Bull. Math. Biol. 62, 483–499 (2000)
J.A.M. Borghans, R.J. De Boer, L.A. Segel, Extending the quasi-steady state approximation by changing variables. Bull. Math. Biol. 58, 43–63 (1996)
A.R. Tzafriri, Michaelis–Menten kinetics at high enzyme concentrations. Bull. Math. Biol. 65, 1111–1129 (2003)
G. Dell’Acqua, A.M. Bersani, A perturbation solution of Michaelis–Menten kinetics in a ‘total’ framework. J. Math. Chem. 50, 1136–1148 (2012)
L.A. Segel, On the validity of the steady state assumption of enzyme kinetics. Bull. Math. Biol. 50, 579–593 (1988)
M.G. Pedersen, A.M. Bersani, E. Bersani, The total quasi-steady-state approximation for fully competitive enzyme reactions. Bull. Math. Biol. 69, 433–457 (2007)
A.M. Bersani, A. Borri, A. Milanesi, P. Vellucci, Tihonov theory and center manifolds for inhibitory mechanisms in enzyme kinetics. Commun. Appl. Ind. Math. 8(1), 81–102 (2017)
A.M. Bersani, A. Borri, A. Milanesi, G. Tomassetti, P. Vellucci, A study case for the analysis of asymptotic expansions beyond the tQSSA for inhibitory mechanisms in enzyme kinetics. Commun. Appl. Ind. Math. 10(1), 162–181 (2019)
A.M. Bersani, A. Borri, A. Milanesi, G. Tomassetti, P. Vellucci, Uniform asymptotic expansions beyond the tQSSA for the Goldbeter-Koshland switch. SIAM J. Appl. Math. 80(3), 1123–1152 (2020)
A.M. Bersani, A. Borri, M.E. Tosti, Singular perturbation techniques and asymptotic expansions for auxiliary enzyme reactions. Continuum Mech. Thermodyn. 33(3), 851–872 (2021)
C.C. Lin, L.A. Segel, Mathematics Applied to Deterministic Problems in the Natural Sciences. Classics in Applied Mathematics (SIAM, Philadelphia, 1988)
S. Schnell, C. Mendoza, Enzyme kinetics of multiple alternative substrates. J. Math. Chem. 27, 155–170 (2000)
S. Rao, P.M. Heynderickx, Conditions for the validity of Michaelis-Menten approximation of some complex enzyme kinetic mechanisms. Biochem. Eng. J. 171, 108007 (2021)
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Besya, A., Rao, S. The total quasi-steady-state for multiple alternative substrate reactions. J Math Chem 60, 841–861 (2022). https://doi.org/10.1007/s10910-022-01339-6
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DOI: https://doi.org/10.1007/s10910-022-01339-6