Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 31100
Mathematical Modeling of Uncompetitive Inhibition of Bi-Substrate Enzymatic Reactions

Authors: Rafayel A. Azizyan, Aram E. Gevorgyan, Valeri B. Arakelyan, Emil S. Gevorgyan


Currently, mathematical and computer modeling are widely used in different biological studies to predict or assess behavior of such a complex systems as a biological are. This study deals with mathematical and computer modeling of bi-substrate enzymatic reactions, which play an important role in different biochemical pathways. The main objective of this study is to represent the results from in silico investigation of bi-substrate enzymatic reactions in the presence of uncompetitive inhibitors, as well as to describe in details the inhibition effects. Four models of uncompetitive inhibition were designed using different software packages. Particularly, uncompetitive inhibitor to the first [ES1] and the second ([ES1S2]; [FS2]) enzyme-substrate complexes have been studied. The simulation, using the same kinetic parameters for all models allowed investigating the behavior of reactions as well as determined some interesting aspects concerning influence of different cases of uncompetitive inhibition. Besides, it has been shown that uncompetitive inhibitors exhibit specific selectivity depending on mechanism of bi-substrate enzymatic reaction. 

Keywords: Mathematical Modeling, bi-substrate enzymatic reactions, ping-pong mechanism, sequential mechanism, uncompetitive inhibition

Digital Object Identifier (DOI):

Procedia APA BibTeX Chicago EndNote Harvard JSON MLA RIS XML ISO 690 PDF Downloads 3180


[1] J. Yon-Kahn, G. Herve. Molecular and Cellular Enzymology. Vol. 1, Springer, 2010.
[2] H. Yuan, G. Fu, Ph. Brooks, I. Weber, G. Gadda, Steady-State Kinetic Mechanism and Reductive Half-Reaction of D-Arginine Dehydrogenase from Pseudomonas aeruginosa. Biochemistry, 2010; 49: 9542–9550.
[3] C. Yao, C. Lai, H. Hsieh, C. Chi, Sh. Yin. Establishment of steady-state metabolism of ethanol in perfused rat liver: the quantitative analysis using kinetic mechanism-based rate equations of alcohol dehydrogenase. Alcohol 2010; 44: 541-551.
[4] H. Bisswanger. Enzyme kinetics. Principles and Methods. 2nd ed. WILEY-VCH, 2008.
[5] T. Keleti. Basic Enzyme Kinetics. Moscow, «Mir», 1990.
[6] W. W. Cleland. Biochim. Biophys. Acta 1963; 67: 104–137.
[7] R. A. Azizyan, A. E. Gevorgyan, V. B. Arakelyan, E. S. Gevorgyan. Computational Modeling of Kinetics of the Bisubstrate Enzymatic Reaction With Ping-pong Mechanism. Biological Journal of Armenia, 2 (64), pp. 85-93.
[8] S. D. Varfolomeev, K. G. Gurevich. Biokinetics. Moscow: «FAIRPRESS », 1999.
[9] R. A. Azizyan, A. E. Gevorgyan, V. B. Arakelyan, E. S. Gevorgyan. Computational Modeling of Kinetics of the Bisubstrate Enzymatic Reaction with Sequential Mechanism. Electronic Journal of Natural Sciences, 1:(18), 2012, pp. 3-8.
[10] A. Cornish-Bowden. Enzyme kinetics from a metabolic perspective. Biochem. Soc. Trans. 27:281–284, 1999.
[11] C. E. Bugg, W. M. Carson and J. A. Montgomery. Drugs by design. Sci. Am. 1993; 269(6): 92–98.
[12] L. A. Moran, H. R. Horton, K. G. Scrimgeour, M. D. Perry. Principles of Biochemistry. 5th ed. Pearson, 2012.
[13] “Mathematica 7” Home page available at URL:
[14] “STELLA Home Page” available at URL: softwares/Education/StellaSoftware.aspx