Modelling the Phosphorylation of Glucose by Human hexokinase I

Vinh Q. Mai and Martin Meere
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Vinh Q. Mai: Department of Mathematics, Thu Dau Mot University, Thu Dau Mot City 820000, Binh Duong, Vietnam
Martin Meere: Department of Applied Mathematics, NUI Galway, H91 TK33 Galway, Ireland

Mathematics, 2021, vol. 9, issue 18, 1-24

Abstract: In this paper, we develop a comprehensive mathematical model to describe the phosphorylation of glucose by the enzyme hexokinase I . Glucose phosphorylation is the first step of the glycolytic pathway, and as such, it is carefully regulated in cells. Hexokinase I phosphorylates glucose to produce glucose-6-phosphate, and the cell regulates the phosphorylation rate by inhibiting the action of this enzyme. The cell uses three inhibitory processes to regulate the enzyme: an allosteric product inhibitory process, a competitive product inhibitory process, and a competitive inhibitory process. Surprisingly, the cellular regulation of hexokinase I is not yet fully resolved, and so, in this study, we developed a detailed mathematical model to help unpack the behaviour. Numerical simulations of the model produced results that were consistent with the experimentally determined behaviour of hexokinase I . In addition, the simulations provided biological insights into the abstruse enzymatic behaviour, such as the dependence of the phosphorylation rate on the concentration of inorganic phosphate or the concentration of the product glucose-6-phosphate. A global sensitivity analysis of the model was implemented to help identify the key mechanisms of hexokinase I regulation. The sensitivity analysis also enabled the development of a simpler model that produced an output that was very close to that of the full model. Finally, the potential utility of the model in assisting experimental studies is briefly indicated.

Keywords: mathematical model; phosphorylation; glucose; hexokinase; sensitivity analysis (search for similar items in EconPapers)
JEL-codes: C (search for similar items in EconPapers)
Date: 2021
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

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