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

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.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.Biosynthesis of the purines AMP and GMP in Escherichia coli is a many-staged process supported by a complex network of enzymes. Some of the genes that encode these enzymes are arranged into operons (purF, purHD, purMN, purEK, guaBA, purB), while others are located in single cistrons (purT, purl, purC, purA, guaC). Expression of these operons is regulated by regulatory proteins (PurR, DnaA, CRP) and various low-molecular-weight compounds [1-3]. The activities of the encoded enzymes are additionally regulated by substrates, reaction products, and certain other low-molecular-weight substances [4,5].The enzyme adenylosuccinate synthetase (AdSS; GDP-forming IMP: L-aspartate ligase, EC 6.3.4.4), which is the product of the purA gene, catalyzes the conversion of IMP to ASUC in the presence of Mg2+:IMP + GTP + ASP → GDP + PI + ASUC.There are many nucleotides that inhibit AdSS. For example, AMP is a competitive inhibitor of IMP; ASUC, of IMP; dGMP, of IMP; GMP, of GTP. GDP is a competitive inhibitor of GTP, which in part explains a gradual decrease in the rate of ASUC formation i