A Database of Thermodynamic Quantities for the Reactions of Glycolysis and the Tricarboxylic Acid Cycle

Abstract

Analysis of biochemical systems requires reliable and self-consistent databases of thermodynamic properties for biochemical reactions. Here a database of thermodynamic properties for the reactions of glycolysis and the tricarboxylic acid cycle is developed from measured equilibrium data. Species-level free energies of formation are estimated based on comparing thermodynamic model predictions for reaction-level equilibrium constants to previously reported data obtained under different experimental conditions. Matching model predictions to the data involves applying state corrections for ionic strength, pH, and metal ion binding for each input experimental biochemical measurement. By archiving all of the raw data, documenting all model assumptions and calculations, and making the computer package and data available, this work provides a framework for extension and refinement by adding to the underlying raw experimental data in the database and/or refining the underlying model assumptions. Thus the resulting database is a refinement of preexisting databases of thermodynamics in terms of reliability, self-consistency, transparency, and extensibility.

Simulation of cellular biochemical system kinetics

“…What is needed is a systematic analysis that uses the information in these databases to provide a set of estimates of thermodynamic properties of chemical species that is optimally consistent with the data. This task is essentially what Li et al 39 have done on a small scale for the reactions of glycolysis and the TCA. The difficulty in expanding this effort to cover significantly more reactions lies in the fact that selecting and parsing the raw data into a form that may be used in computational analysis require the effort of a human expert.…”

“…This task is essentially what Li et al . [39] have done on a small scale for the reactions of glycolysis and the tricarboxylic acid cycle. The difficulty in expanding this effort to cover significantly more reactions lies in the fact that selecting and parsing the raw data into a form that may be used in computational analysis requires the effort of a human expert.…”

Identification of the kinetic mechanism of succinyl-CoA synthetase

“…For each data point, ionic strength was estimated based on estimating the free ion concentration of each species in the buffer on the basis of mass and charge balances [20]. Estimated ionic strength ranges are reported in the legends to Figures 3, 4 and 6.…”

“…Accounting for the experimental temperature of the Cha and Parks data [8,27] ( T =303.15 K) the standard Gibbs free energy of reaction at 303.15 K computed from the reported thermodynamic data in Table 1 (i.e. after temperature correction [20]) is Δ r G 0 =56.98 kJ/mol. Thus there is a difference of 1.83 kJ/mol between the Gibbs free energy associated with the optimal kinetic parameters and the estimate reported in Li et al [19].…”

“…The binding polynomial for reactant j is a function of the pH and free concentrations of metal cations [19]: $\begin{array}{ccc}trueright{P}_j& =& left1+\frac{h}{K_{h1,j}}+\frac{h^2}{K_{h1,j}{K}_{h2,j}}+\frac{\left[{\mathrm{Mg}}^{2+}\right]}{K_{\mathrm{Mg}1,j}}+\frac{h\left[{\mathrm{Mg}}^{2+}\right]}{K_{h1,j}{K}_{h\mathrm{Mg},j}}\\ & & left+\frac{{\left[{\mathrm{Mg}}^{2+}\right]}^2}{K_{\mathrm{Mg}1,j}{K}_{\mathrm{Mg}2,j}}+\cdots \end{array}$ where h is the hydrogen ion activity ( h =10 − pH ), and the K values represent cation dissociation constants, obtained from Li et al [19]. For the calculations used here, all values are corrected for the effects of temperature and ionic strength as detailed in Li et al [20]. Thermodynamic data used in this study are listed in Table 1.…”