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

A simple two-carbon compound may have been a crucial player in the evolution of metabolism before the advent of cells, according to a new study published Oct. 4 in the open access journal. PLOS Biologyby Nick Lane and colleagues from University College London, UK The finding may shed light on the earliest stages of prebiotic biochemistry and suggest how ATP has become the universal energy carrier of all cellular life today.

ATP, adenosine triphosphate, is used by all cells as an energy intermediate. During cellular respiration, energy is captured when a phosphate is added to ADP (adenosine diphosphate) to generate ATP; cleavage of that phosphate releases energy to power most types of cellular functions. But rebuilding ATP’s complex chemical structure from scratch is energy-intensive and requires six separate ATP-driven steps; although convincing models allow prebiotic formation of the ATP skeleton without energy from already formed ATP, they also suggest that ATP was probably quite scarce and that another compound may have played a central role in the conversion of ADP to ADP at this stage of evolution.

The most likely candidate, Lane and colleagues believed, was the two-carbon compound acetyl phosphate (AcP), which today acts 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 after that demonstration, numerous questions remained, including whether other small molecules might work as well, whether AcP is specific for ADP or instead is just like that. could function. interacts well with diphosphates of other nucleosides (such as guanosine or cytosine), and whether iron is unique in its ability to catalyze ADP phosphorylation in water.

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

Combining these results with molecular dynamic modelling, the authors propose a mechanistic explanation for the specificity of the ADP/AcP/iron reaction, assuming that the small diameter and high charge density of the iron ion, combined with the conformation of the intermediate formed when the three come together, providing a “just right” geometry that allows AcP’s phosphate to switch partners, forming ATP.

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

Lead author Silvana Pinna added: “ATP plays such a central role in metabolism that I thought it might be possible to form it from ADP under prebiotic conditions. But I also thought that various phosphorylating agents and metal ion catalysts would work, especially those that are preserved in life. It was very surprising to find that the reaction is so selective – in the metal ion, the phosphate donor and the substrate – with molecules that life still uses. The fact that this happens best in water under mild, life-compatible conditions is really very important to the origin of life.”