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Updated: Oct 15, 2025

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Thermodynamics of Potential CHO Metabolites in a Reducing Environment
Jeremy Kua1, Alexandra L Hernandez1, Danielle N Velasquez1
1Department of Chemistry & Biochemistry, University of San Diego, San Diego, CA 92110, USA.
Abstract:
How did metabolism arise and evolve? What chemical compounds might be suitable to support and sustain a proto-metabolism before the advent of more complex co-factors? We explore these questions by using first-principles quantum chemistry to calculate the free energies of CHO compounds in aqueous solution, allowing us to probe the thermodynamics of core extant cycles and their closely related chemical cousins. By framing our analysis in terms of the simplest feasible cycle and its permutations, we analyze potentially favorable thermodynamic cycles for CO2 fixation with H2 as a reductant. We find that paying attention to redox states illuminates which reactions are endergonic or exergonic. Our results highlight the role of acetate in proto-metabolic cycles, and its connection to other prebiotic molecules such as glyoxalate, glycolaldehyde, and glycolic acid.
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