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Uncertainty of prebiotic scenarios: the case of the non-enzymatic reverse tricarboxylic acid cycle.

Zubarev DY, Rappoport D, Aspuru-Guzik A - Sci Rep (2015)

Bottom Line: We consider the hypothesis of the primordial nature of the non-enzymatic reverse tricarboxylic acid (rTCA) cycle and describe a modeling approach to quantify the uncertainty of this hypothesis due to the combinatorial aspect of the constituent chemical transformations.Our results suggest that a) rTCA cycle belongs to a degenerate optimum of auto-catalytic cycles, and b) the set of targets for investigations of the origin of the common metabolic core should be significantly extended.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA.

ABSTRACT
We consider the hypothesis of the primordial nature of the non-enzymatic reverse tricarboxylic acid (rTCA) cycle and describe a modeling approach to quantify the uncertainty of this hypothesis due to the combinatorial aspect of the constituent chemical transformations. Our results suggest that a) rTCA cycle belongs to a degenerate optimum of auto-catalytic cycles, and b) the set of targets for investigations of the origin of the common metabolic core should be significantly extended.

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Stability and reducing potential of the molecules in the rTCA supernetwork.Thermodynamic values are computed in aqueous solution (see Methods). H2/CO2 designates reducing potential of molecule A defined as y/x following equation xCO2 + yH2 → A + zH2O. The crosses represent all molecules in the supernetwork. Empty circles over crosses represent the molecules from the cycles similar to rTCA cycle with 11 molecules and 1 branching point. The filled circles represent the molecules of rTCA cycle. Panel A: A counterpart of the Figure 2 from Ref. 3; computed free energies of formation are used instead of experimental. Free energy of formation per carbon atom is plotted against degree of reduction. Panel B: Free energy of formation vs. degree of reduction. Panel C: Free energy of formation vs. free energy of formation per carbon atom. The dataset is strongly stratified according to the number of carbon atoms from 1 to 7, from the top of the plot.
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f4: Stability and reducing potential of the molecules in the rTCA supernetwork.Thermodynamic values are computed in aqueous solution (see Methods). H2/CO2 designates reducing potential of molecule A defined as y/x following equation xCO2 + yH2 → A + zH2O. The crosses represent all molecules in the supernetwork. Empty circles over crosses represent the molecules from the cycles similar to rTCA cycle with 11 molecules and 1 branching point. The filled circles represent the molecules of rTCA cycle. Panel A: A counterpart of the Figure 2 from Ref. 3; computed free energies of formation are used instead of experimental. Free energy of formation per carbon atom is plotted against degree of reduction. Panel B: Free energy of formation vs. degree of reduction. Panel C: Free energy of formation vs. free energy of formation per carbon atom. The dataset is strongly stratified according to the number of carbon atoms from 1 to 7, from the top of the plot.

Mentions: The similar picture emerges from the analysis of the redox properties of the molecules in the supernetwork. Previously-proposed conclusions about the predisposed nature of rTCA cycle3 in part relied on the analysis of intensive characteristics of the rTCA cycle molecules such as thermodynamic stability per carbon atom and degree of reduction per carbon atom. Following Ref. 3, we define the reducing potential per carbon atom taken from the environment to form molecule A as the ratio y/x determined from a formal reaction xCO2 + yH2 → A + zH2O. As a counterpart of Figure 2 in Ref. 3, Figure 4A shows theoretical estimates of the free energy of formation computed in aqueous solution (see Methods) per carbon atom plotted against reducing potential for all molecules of the generated supernetwork. Molecules of rTCA cycle belong to the central part of a broad distribution and have neighbors with comparable or more favorable combinations of stability and reducing potential. For example, the cycles obtained by permutations of reductive carboxylation and carboxylation steps (Fig. 5A) would qualify as more favorable on thermodynamic grounds. They proceed via malonate which is more stable than pyruvate with −176 vs. −114 kcal/mol per 3 carbon atoms, and/or 1, 1, 2-ethanetricarboxylate that is more stable than 2-ketoglutarate with −254 vs. −199 kcal/mol per 5 carbon atoms.


Uncertainty of prebiotic scenarios: the case of the non-enzymatic reverse tricarboxylic acid cycle.

Zubarev DY, Rappoport D, Aspuru-Guzik A - Sci Rep (2015)

Stability and reducing potential of the molecules in the rTCA supernetwork.Thermodynamic values are computed in aqueous solution (see Methods). H2/CO2 designates reducing potential of molecule A defined as y/x following equation xCO2 + yH2 → A + zH2O. The crosses represent all molecules in the supernetwork. Empty circles over crosses represent the molecules from the cycles similar to rTCA cycle with 11 molecules and 1 branching point. The filled circles represent the molecules of rTCA cycle. Panel A: A counterpart of the Figure 2 from Ref. 3; computed free energies of formation are used instead of experimental. Free energy of formation per carbon atom is plotted against degree of reduction. Panel B: Free energy of formation vs. degree of reduction. Panel C: Free energy of formation vs. free energy of formation per carbon atom. The dataset is strongly stratified according to the number of carbon atoms from 1 to 7, from the top of the plot.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4306138&req=5

f4: Stability and reducing potential of the molecules in the rTCA supernetwork.Thermodynamic values are computed in aqueous solution (see Methods). H2/CO2 designates reducing potential of molecule A defined as y/x following equation xCO2 + yH2 → A + zH2O. The crosses represent all molecules in the supernetwork. Empty circles over crosses represent the molecules from the cycles similar to rTCA cycle with 11 molecules and 1 branching point. The filled circles represent the molecules of rTCA cycle. Panel A: A counterpart of the Figure 2 from Ref. 3; computed free energies of formation are used instead of experimental. Free energy of formation per carbon atom is plotted against degree of reduction. Panel B: Free energy of formation vs. degree of reduction. Panel C: Free energy of formation vs. free energy of formation per carbon atom. The dataset is strongly stratified according to the number of carbon atoms from 1 to 7, from the top of the plot.
Mentions: The similar picture emerges from the analysis of the redox properties of the molecules in the supernetwork. Previously-proposed conclusions about the predisposed nature of rTCA cycle3 in part relied on the analysis of intensive characteristics of the rTCA cycle molecules such as thermodynamic stability per carbon atom and degree of reduction per carbon atom. Following Ref. 3, we define the reducing potential per carbon atom taken from the environment to form molecule A as the ratio y/x determined from a formal reaction xCO2 + yH2 → A + zH2O. As a counterpart of Figure 2 in Ref. 3, Figure 4A shows theoretical estimates of the free energy of formation computed in aqueous solution (see Methods) per carbon atom plotted against reducing potential for all molecules of the generated supernetwork. Molecules of rTCA cycle belong to the central part of a broad distribution and have neighbors with comparable or more favorable combinations of stability and reducing potential. For example, the cycles obtained by permutations of reductive carboxylation and carboxylation steps (Fig. 5A) would qualify as more favorable on thermodynamic grounds. They proceed via malonate which is more stable than pyruvate with −176 vs. −114 kcal/mol per 3 carbon atoms, and/or 1, 1, 2-ethanetricarboxylate that is more stable than 2-ketoglutarate with −254 vs. −199 kcal/mol per 5 carbon atoms.

Bottom Line: We consider the hypothesis of the primordial nature of the non-enzymatic reverse tricarboxylic acid (rTCA) cycle and describe a modeling approach to quantify the uncertainty of this hypothesis due to the combinatorial aspect of the constituent chemical transformations.Our results suggest that a) rTCA cycle belongs to a degenerate optimum of auto-catalytic cycles, and b) the set of targets for investigations of the origin of the common metabolic core should be significantly extended.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA.

ABSTRACT
We consider the hypothesis of the primordial nature of the non-enzymatic reverse tricarboxylic acid (rTCA) cycle and describe a modeling approach to quantify the uncertainty of this hypothesis due to the combinatorial aspect of the constituent chemical transformations. Our results suggest that a) rTCA cycle belongs to a degenerate optimum of auto-catalytic cycles, and b) the set of targets for investigations of the origin of the common metabolic core should be significantly extended.

Show MeSH
Related in: MedlinePlus