Mathematical modeling of Bi-Substrate Enzymatic Reactions with Ping-Pong Mechanism in the Presence of Competitive Inhibitors
The mathematical modeling of different biological
processes is usually used to predict or assess behavior of systems in
which these processes take place. This study deals with mathematical
and computer modeling of bi-substrate enzymatic reactions with
ping-pong mechanism, which play an important role in different
biochemical pathways. Besides that, three models of competitive
inhibition were designed using different software packages. The main
objective of this study is to represent the results from in silico
investigation of bi-substrate enzymatic reactions with ordered pingpong
mechanism in the presence of competitive inhibitors, as well as
to describe in details the inhibition effects. The simulation of the
models with certain kinetic parameters allowed investigating the
behavior of reactions as well as determined some interesting aspects
concerning influence of different cases of competitive inhibition.
Simultaneous presence of two inhibitors, competitive to the S1 and S2
substrates have been studied. Moreover, we have found the pattern of
simultaneous influence of both inhibitors.
[1] 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.
[2] 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.
[3] J. Yon-Kahn, G. Herve. Molecular and Cellular Enzymology. Vol. 1,
Springer, 2010.
[4] H. Bisswanger. Enzyme kinetics. Principles and Methods. 2nd ed.
WILEY-VCH, 2008.
[5] W. W. Cleland. Biochim. Biophys. Acta 1963; 67: 104-137.
[6] T. Keleti. Basic Enzyme Kinetics. Moscow, «Mir», 1990.
[7] S. D. Varfolomeev, K. G. Gurevich. Biokinetics. Moscow: «FAIRPRESS
», 1999.
[8] "Mathematica 7" Home page available at
URL:http://www.wolfram.com/products/mathematica/newin7
[9] "STELLA Home Page" available at URL:
http://www.iseesystems.com/softwares/Education/StellaSoftware.aspx
[10] 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
[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.
[1] 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.
[2] 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.
[3] J. Yon-Kahn, G. Herve. Molecular and Cellular Enzymology. Vol. 1,
Springer, 2010.
[4] H. Bisswanger. Enzyme kinetics. Principles and Methods. 2nd ed.
WILEY-VCH, 2008.
[5] W. W. Cleland. Biochim. Biophys. Acta 1963; 67: 104-137.
[6] T. Keleti. Basic Enzyme Kinetics. Moscow, «Mir», 1990.
[7] S. D. Varfolomeev, K. G. Gurevich. Biokinetics. Moscow: «FAIRPRESS
», 1999.
[8] "Mathematica 7" Home page available at
URL:http://www.wolfram.com/products/mathematica/newin7
[9] "STELLA Home Page" available at URL:
http://www.iseesystems.com/softwares/Education/StellaSoftware.aspx
[10] 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
[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.
@article{"International Journal of Biological, Life and Agricultural Sciences:58729", author = "Rafayel A. Azizyan and Aram E. Gevogyan and Valeri B. Arakelyan and Emil S. Gevorgyan", title = "Mathematical modeling of Bi-Substrate Enzymatic Reactions with Ping-Pong Mechanism in the Presence of Competitive Inhibitors", abstract = "The mathematical modeling of different biological
processes is usually used to predict or assess behavior of systems in
which these processes take place. This study deals with mathematical
and computer modeling of bi-substrate enzymatic reactions with
ping-pong mechanism, which play an important role in different
biochemical pathways. Besides that, three models of competitive
inhibition were designed using different software packages. The main
objective of this study is to represent the results from in silico
investigation of bi-substrate enzymatic reactions with ordered pingpong
mechanism in the presence of competitive inhibitors, as well as
to describe in details the inhibition effects. The simulation of the
models with certain kinetic parameters allowed investigating the
behavior of reactions as well as determined some interesting aspects
concerning influence of different cases of competitive inhibition.
Simultaneous presence of two inhibitors, competitive to the S1 and S2
substrates have been studied. Moreover, we have found the pattern of
simultaneous influence of both inhibitors.", keywords = "Mathematical modeling, bi-substrate enzymatic reactions, ping-pong mechanism, competitive inhibition.", volume = "7", number = "2", pages = "115-3", }