Ancient chemistry may explain why living things use ATP as a universal energy currency

A simple two-carbon compound may have been an important player in the evolution of metabolism before the appearance of cells, according to a new study published Oct. 4 in the journal Open Access. PLOS BiologyNick Lane and colleagues from University College London, UK. The finding potentially sheds light on the earliest stages of prebiotic biochemistry and demonstrates how ATP has become the universal energy carrier of all cellular life today.

ATP, adenosine triphosphateused by all cells as an energy intermediate. During cellular respirationenergy is captured when a phosphate is added to ADP (adenosine diphosphate) to produce ATP; the breakdown of this phosphate releases energy to power most types of cellular functions. But creating the complex chemical structure of ATP from scratch is energy-intensive and requires six separate ATP-driven steps; while compelling models allow prebiotic formation of the ATP skeleton without energy from already formed ATP, they also suggest that ATP was probably very scarce and that some other compound may have played a central role in the conversion of ADP to ADP at this stage of evolution.

Lane and his colleagues believed that the most likely candidate was the two-carbon compound acetyl phosphate (AcP), which today functions as a metabolic intermediate in both bacteria and archaea. AcP has been shown to phosphorylate ADP to ATP in water in the presence of iron ions, but many questions remain after this demonstration, including whether other small molecules may also work, regardless of whether AcP is specific for ADP, can instead work just as well with diphosphates of other nucleosides (such as guanosine or cytosine), and whether iron is unique in its ability to catalyze ADP phosphorylation in the water.

In their new study, the authors investigated all these questions. Based on data and hypotheses about the chemical conditions of Earth before the origin of life, they tested the ability of other ions and minerals to catalyze the formation of ATP in water; none were as effective as iron. They then tested a group of other small organic molecules for their ability to phosphorylate ADP; none were as effective as AcP, and only one other (carbamoyl phosphate) had any significant activity at all. Finally, they showed that none of the other nucleoside diphosphates accept phosphate from AcP.

Combining these results with molecular dynamics simulations, the authors propose a mechanistic explanation for the specificity of the ADP/AcP/iron reaction, suggesting that the small diameter and high charge density of the iron ion, combined with the conformation of the intermediate formed when the three combine to provide ” “the most correct” geometry that allows the AcP phosphate to switch partners to form ATP.

“Our results show that AcP is the most likely precursor to ATP as a biological phosphorylator,” says Lane, “and that the emergence of ATP as the cell’s universal energy currency was not a result of ‘frozen chance’ but arose from unique interactions between ADP and AcP . Over time, with the advent of suitable catalysts, ATP may eventually supplant AcP as the ubiquitous phosphate donor and promote the polymerization of amino acids and nucleotides to form RNA, DNA, and proteins.”

Lead author Silvana Pino adds, “ATP is so central to metabolism that I thought it might be possible to generate it from ADP under prebiotic conditions. But I also thought that a few phosphorylating agents and metal ion catalysts would work, especially those that last a lifetime. It was very surprising to find that the reaction is so selective – in metal ion, phosphate donor and substrate – with molecules that life still uses. The fact that this happens best in water in soft, life-compatible conditions is really important for the origin of life.”