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A mathematical model for the adenylosuccinate synthetase reaction involved in purine biosynthesis.

Oshchepkova-Nedosekina EA, Likhoshvai VA - Theor Biol Med Model (2007)

Bottom Line: The advantage of our model is that it includes relationships between the reaction rate, the concentrations of three substrates (GTP, IMP and ASP), the effects of five inhibitors (GMP, GDP, AMP, ASUC and SUCC), and the influence of Mg2+ ions.The model was tested for adequacy using experimental data published elsewhere.The values obtained for the parameters are as follows: Vmax = 1.35.10-3 mM/min, KmGTP = 0.023 mM, KmIMP = 0.02 mM, KmASP = 0.3 mM, KiGMP = 0.024 mM, KiGDP = 8.10-3 mM, KiAMP = 0.01 mM, KiASUC = 7.5.10-3 mM, KiSUCC = 8 mM, KmMg = 0.08 mM.

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Affiliation: Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia. nzhenia@bionet.nsc.ru

ABSTRACT

Background: Development of the mathematical models that adequately describe biochemical reactions and molecular-genetic mechanisms is one of the most important tasks in modern bioinformatics. Because the enzyme adenylosuccinate synthetase (AdSS) has long been extensively studied, a wealth of kinetic data has been accumulated.

Results: We describe a mathematical model for the reaction catalyzed by AdSS. The model's parameters were fitted to experimental data obtained from published literature. The advantage of our model is that it includes relationships between the reaction rate, the concentrations of three substrates (GTP, IMP and ASP), the effects of five inhibitors (GMP, GDP, AMP, ASUC and SUCC), and the influence of Mg2+ ions.

Conclusion: Our model describes the reaction catalyzed by AdSS as a fully random process. The model structure implies that each of the inhibitors included in it is only competitive to one of the substrates. The model was tested for adequacy using experimental data published elsewhere. The values obtained for the parameters are as follows: Vmax = 1.35.10-3 mM/min, KmGTP = 0.023 mM, KmIMP = 0.02 mM, KmASP = 0.3 mM, KiGMP = 0.024 mM, KiGDP = 8.10-3 mM, KiAMP = 0.01 mM, KiASUC = 7.5.10-3 mM, KiSUCC = 8 mM, KmMg = 0.08 mM.

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Relationships between the reaction rate and concentration of Mg2+ ions at varying concentrations of ASP. Experimental data from [9].
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Figure 4: Relationships between the reaction rate and concentration of Mg2+ ions at varying concentrations of ASP. Experimental data from [9].

Mentions: The influence of Mg2+ ions on enzyme activity is included in our model on the basis of the kinetic curves presented in the work of Kang and Fromm [9]. The concentration of Mg2+ is included as a multiplier in the form of a simple rational fraction raised to the first power. Kang and Fromm also included the concentration of Mg2+ as a multiplier raised to the first power; however, they additionally assumed that Mg2+ and ASP may act cooperatively. Our calculations demonstrate that an even simpler model, which does not assume Mg2+/ASP synergy, is adequate for describing the influence of magnesium. Although our model does not say that there are two binding sites for Mg2+ ions, nor does it say otherwise [12], for it is not necessary that Hill's number be the same as the number of ligand-binding centers in the enzyme. Using our model, KmMg is 0.08 mM (Fig. 4).


A mathematical model for the adenylosuccinate synthetase reaction involved in purine biosynthesis.

Oshchepkova-Nedosekina EA, Likhoshvai VA - Theor Biol Med Model (2007)

Relationships between the reaction rate and concentration of Mg2+ ions at varying concentrations of ASP. Experimental data from [9].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1808444&req=5

Figure 4: Relationships between the reaction rate and concentration of Mg2+ ions at varying concentrations of ASP. Experimental data from [9].
Mentions: The influence of Mg2+ ions on enzyme activity is included in our model on the basis of the kinetic curves presented in the work of Kang and Fromm [9]. The concentration of Mg2+ is included as a multiplier in the form of a simple rational fraction raised to the first power. Kang and Fromm also included the concentration of Mg2+ as a multiplier raised to the first power; however, they additionally assumed that Mg2+ and ASP may act cooperatively. Our calculations demonstrate that an even simpler model, which does not assume Mg2+/ASP synergy, is adequate for describing the influence of magnesium. Although our model does not say that there are two binding sites for Mg2+ ions, nor does it say otherwise [12], for it is not necessary that Hill's number be the same as the number of ligand-binding centers in the enzyme. Using our model, KmMg is 0.08 mM (Fig. 4).

Bottom Line: The advantage of our model is that it includes relationships between the reaction rate, the concentrations of three substrates (GTP, IMP and ASP), the effects of five inhibitors (GMP, GDP, AMP, ASUC and SUCC), and the influence of Mg2+ ions.The model was tested for adequacy using experimental data published elsewhere.The values obtained for the parameters are as follows: Vmax = 1.35.10-3 mM/min, KmGTP = 0.023 mM, KmIMP = 0.02 mM, KmASP = 0.3 mM, KiGMP = 0.024 mM, KiGDP = 8.10-3 mM, KiAMP = 0.01 mM, KiASUC = 7.5.10-3 mM, KiSUCC = 8 mM, KmMg = 0.08 mM.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia. nzhenia@bionet.nsc.ru

ABSTRACT

Background: Development of the mathematical models that adequately describe biochemical reactions and molecular-genetic mechanisms is one of the most important tasks in modern bioinformatics. Because the enzyme adenylosuccinate synthetase (AdSS) has long been extensively studied, a wealth of kinetic data has been accumulated.

Results: We describe a mathematical model for the reaction catalyzed by AdSS. The model's parameters were fitted to experimental data obtained from published literature. The advantage of our model is that it includes relationships between the reaction rate, the concentrations of three substrates (GTP, IMP and ASP), the effects of five inhibitors (GMP, GDP, AMP, ASUC and SUCC), and the influence of Mg2+ ions.

Conclusion: Our model describes the reaction catalyzed by AdSS as a fully random process. The model structure implies that each of the inhibitors included in it is only competitive to one of the substrates. The model was tested for adequacy using experimental data published elsewhere. The values obtained for the parameters are as follows: Vmax = 1.35.10-3 mM/min, KmGTP = 0.023 mM, KmIMP = 0.02 mM, KmASP = 0.3 mM, KiGMP = 0.024 mM, KiGDP = 8.10-3 mM, KiAMP = 0.01 mM, KiASUC = 7.5.10-3 mM, KiSUCC = 8 mM, KmMg = 0.08 mM.

Show MeSH