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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.

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.

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Relationships between the reaction rate and the concentration of GTP in the presence of SUCC. SUCC concentrations were (black line and circles) 50 mM; (red line and circles) 25 mM; (brown line and circles) 12.5 mM; (crimson line and circles) 0. Experimental data from [7].
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Figure 1: Relationships between the reaction rate and the concentration of GTP in the presence of SUCC. SUCC concentrations were (black line and circles) 50 mM; (red line and circles) 25 mM; (brown line and circles) 12.5 mM; (crimson line and circles) 0. Experimental data from [7].

Mentions: In 1995, Kang and Fromm investigated the influence of Mg2+ ions on the AdSS-catalyzed reaction [9]. It was demonstrated that for AdSS to be in the activated form, two Mg2+ ions are required. One interacts with the β- and γ-phosphoryl groups of GTP, the other with the aspartate in the enzyme's active center, improving the affinity of the enzyme for ASP. Kinetic experiments on the interactions of Mg2+ and ASP were performed with saturating concentrations of GTP and IMP, so the GTP and IMP concentrations were not included in the model. Although the authors themselves proved that AdSS has two binding centers for Mg2+, the model treats the Mg2+ concentration as if there were only one (at least this is how we interpret the presence of ion concentration as an item raised to the first power). The initial velocity in the Hill plot (Fig. 1 in [9]) was measured at saturating concentrations of IMP, GTP and Asp with Mg2+ varying.


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 the concentration of GTP in the presence of SUCC. SUCC concentrations were (black line and circles) 50 mM; (red line and circles) 25 mM; (brown line and circles) 12.5 mM; (crimson line and circles) 0. Experimental data from [7].
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Relationships between the reaction rate and the concentration of GTP in the presence of SUCC. SUCC concentrations were (black line and circles) 50 mM; (red line and circles) 25 mM; (brown line and circles) 12.5 mM; (crimson line and circles) 0. Experimental data from [7].
Mentions: In 1995, Kang and Fromm investigated the influence of Mg2+ ions on the AdSS-catalyzed reaction [9]. It was demonstrated that for AdSS to be in the activated form, two Mg2+ ions are required. One interacts with the β- and γ-phosphoryl groups of GTP, the other with the aspartate in the enzyme's active center, improving the affinity of the enzyme for ASP. Kinetic experiments on the interactions of Mg2+ and ASP were performed with saturating concentrations of GTP and IMP, so the GTP and IMP concentrations were not included in the model. Although the authors themselves proved that AdSS has two binding centers for Mg2+, the model treats the Mg2+ concentration as if there were only one (at least this is how we interpret the presence of ion concentration as an item raised to the first power). The initial velocity in the Hill plot (Fig. 1 in [9]) was measured at saturating concentrations of IMP, GTP and Asp with Mg2+ varying.

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.

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