Review
doi: 10.1073/pnas.0404922101. Epub 2004 Aug 30.Universality in intermediary metabolism
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- PMID:15340153
- PMCID: PMC516543
- DOI: 10.1073/pnas.0404922101
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Review
Universality in intermediary metabolism
Eric Smith et al. Proc Natl Acad Sci U S A..
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Abstract
We analyze the stoichiometry, energetics, and reaction concentration dependence of the reductive tricarboxylic acid (rTCA) cycle as a universal and possibly primordial metabolic core. The rTCA reaction sequence is a network-autocatalytic cycle along the relaxation pathway for redox couples in nonequilibrium reducing environments, which provides starting organic compounds for the synthesis of all major classes of biomolecules. The concentration dependence of its reactions suggests it as a precellular bulk process. We propose that rTCA is statistically favored among competing redox relaxation pathways under early-earth conditions and that this feature drove its emergence and also accounts for its evolutionary robustness and universality. The ability to enhance the rate of core reactions creates an energetic basis for selection of subsequent layers of biological complexity.
Figures
The reductive TCA cycle (boldface) as an engine of synthesis of the major classes of biomolecules (bold italic). Synthesis of categories usually begins with a specific molecule (lightface).
ΔfG0 in kJ/mol per carbon atom of TCA cycle intermediates from CO2(aq) and H2(aq), together with reference molecules on the reduction pathway to CH4(aq). For the reactionxCO2 +yH2 ⇋X +zH2O, reducing potential per carbon taken from the environment to form speciesX is plotted asy/x on the abscissa. ΔfG0 values for cycle intermediates from ref. and for other organic compounds from ref. .
The rTCA cycle reactions. Synthesis from acetate → fumarate is repeated from succinate →cis-aconitate, with CH2COOH replacing H as end group. ΔrG0 values (kJ/mol, bold italic) are for reactions from CO2(aq) and H2(aq) in equilibrium with gases at 1atm partial pressure, and H2O(l). Computed from ΔfG0 values in ref. , using ΔfG0 =–386 kJ/Mol for CO2(aq), +17.7 kJ/Mol for H2(aq), and –237.2 kJ/Mol for H2O(l). ΔrG0 =–34 kJ/Mol for ATP hydrolysis corresponds to a local stationary region ≈pH 6 and pMg 1.5 in ref. .
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