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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 ASP concentration in the presence/absence of ASUC. Experimental data from [7].
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Figure 3: Relationships between the reaction rate and the ASP concentration in the presence/absence of ASUC. Experimental data from [7].

Mentions: Wyngaarden and Greenland [6] investigated the effect of ASUC, another inhibitor, and proposed that it is competitive with both IMP and ASP. Likewise, it was proposed that GMP is a competitive inhibitor of both IMP and GTP. However, our calculations suggest that ASUC appears to be competitive with only IMP, and GMP with only GTP. The effects of ASUC on IMP and ASP and the model output are presented in Figs. 2, 3. Using the model, KiASUC is 7.5·10-3 mM.


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 ASP concentration in the presence/absence of ASUC. Experimental data from [7].
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Relationships between the reaction rate and the ASP concentration in the presence/absence of ASUC. Experimental data from [7].
Mentions: Wyngaarden and Greenland [6] investigated the effect of ASUC, another inhibitor, and proposed that it is competitive with both IMP and ASP. Likewise, it was proposed that GMP is a competitive inhibitor of both IMP and GTP. However, our calculations suggest that ASUC appears to be competitive with only IMP, and GMP with only GTP. The effects of ASUC on IMP and ASP and the model output are presented in Figs. 2, 3. Using the model, KiASUC is 7.5·10-3 mM.

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
Related in: MedlinePlus