Reactivity of Metabolic Intermediates and Cofactor Stability under Model Early Earth Conditions

Abstract

Understanding the emergence of metabolic pathways is key to unraveling the factors that promoted the origin of life. One popular view is that protein cofactors acted as catalysts prior to the evolution of the protein enzymes with which they are now associated. We investigated the stability of acetyl coenzyme A (Acetyl Co-A, the group transfer cofactor in citric acid synthesis in the TCA cycle) under early Earth conditions, as well as whether Acetyl Co-A or its small molecule analogs thioacetate or acetate can catalyze the transfer of an acetyl group onto oxaloacetate in the absence of the citrate synthase enzyme. Several different temperatures, pH ranges, and compositions of aqueous environments were tested to simulate the Earth’s early ocean and its possible components; the effect of these variables on oxaloacetate and cofactor chemistry were assessed under ambient and anoxic conditions. The cofactors tested are chemically stable under early Earth conditions, but none of the three compounds (Acetyl Co-A, thioacetate, or acetate) promoted synthesis of citric acid from oxaloacetate under the conditions tested. Oxaloacetate reacted with itself and/or decomposed to form a sequence of other products under ambient conditions, and under anoxic conditions was more stable; under ambient conditions the specific chemical pathways observed depended on the environmental conditions such as pH and presence/absence of bicarbonate or salt ions in early Earth ocean simulants. This work demonstrates the stability of these metabolic intermediates under anoxic conditions. However, even though free cofactors may be stable in a geological environmental setting, an enzyme or other mechanism to promote reaction specificity would likely be necessary for at least this particular reaction to proceed.

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Acknowledgements

This work was supported by the NASA Astrobiology Program under the Joint NASA-NSF Ideas Lab on the Origins of Life (NSF Solicitation 16-570) (LMB, ADG, DEL). TRM and LMB were supported by a JPL Spontaneous Research and Technology Development Award. We thank Bryana Henderson for assistance with mass spectrometry analysis, Oak Crest Institute of Science for GC-MS analysis, and Jessica Weber for helpful discussions. This work was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration. Financial assistance was provided to DEL by the Center for Dark Energy Biosphere Investigations (C-DEBI; award OCE0939564) and the NASA Astrobiology Institute — Life Underground (NAI-LU; award NNA13AA92A). This is C-DEBI contribution 521 and NAI-LU contribution 140. Copyright 2019 California Institute of Technology, all rights reserved.

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Maltais, T.R., VanderVelde, D., LaRowe, D.E. et al. Reactivity of Metabolic Intermediates and Cofactor Stability under Model Early Earth Conditions. Orig Life Evol Biosph 50, 35–55 (2020). https://doi.org/10.1007/s11084-019-09590-9

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Keywords

  • Acetyl coenzyme a
  • TCA cycle
  • Oxaloacetate
  • Metabolism
  • Early earth