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

• Published in: Origins of life and evolution of biospheres Vol. 50; no. 1-2; pp. 35 - 55
• Main Authors: Maltais, Thora R., VanderVelde, David, LaRowe, Douglas E., Goldman, Aaron D., Barge, Laura M.
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01-06-2020; Springer Nature B.V
• Subjects: Acetates - chemistry; Acetic acid; Acetyl Coenzyme A - chemistry; Analogs; Anoxic conditions; Astronomy; Astrophysics and Astroparticles; Bicarbonates; Biochemistry; Biomedical and Life Sciences; Catalysis; Catalysts; Citrate (si)-Synthase - chemistry; Citrate synthase; Citric acid; Coenzyme A; Cofactors; Earth; Earth Sciences; Earth, Planet; Environmental conditions; Enzymes; Intermediates; Life Sciences; Metabolic pathways; Metabolism; Observations and Techniques; Oceans; Origin of life; Oxaloacetic Acid - chemistry; pH effects; Prebiotic Chemistry; Space life sciences; Sulfhydryl Compounds - chemistry; Tricarboxylic acid cycle; Acetyl coenzyme a; Oxaloacetate; Metabolism; TCA cycle; Early earth
• ISSN: 0169-6149; 1573-0875
• DOI: 10.1007/s11084-019-09590-9

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.