Ancient Chemistry: Why living things use ATP as their universal energy currency

An early step in metabolic evolution paved the way for the emergence of ATP as a universal fuel.

A simple two-carbon compound may have been a key player in the evolution of metabolism before the advent of cells. That’s according to a new study by Nick Lane and colleagues from University College London, UK, published in the Open Access Journal PLOS biology on October 4th^th. The discovery may provide important insights into the earliest stages of prebiotic biochemistry. In addition, the finding indicates how ATP (adenosine triphosphate) became the universal energy carrier of all cellular life today.

ATP is used by all cells as an intermediate energy product. During cellular respiration, energy is gained when a phosphate is added to ADP (adenosine diphosphate) to create ATP. The breakdown of this phosphate releases energy to power most types of cellular functions.

However, building the complex chemical structure of ATP from scratch is energy intensive and requires six separate ATP-driven steps. While compelling models allow for prebiotic formation of the ATP skeleton without energy from already formed ATP, they also indicate that ATP was probably quite scarce. This means that at this stage of evolution another compound may have played a central role in converting ADP to ATP.

The most likely candidate, Lane and colleagues believed, was the two-carbon compound acetyl phosphate (AcP), which now 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 a number of questions remained after this demonstration, including whether other small molecules might also work, whether AcP is specific for ADP, or might 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 water.

Molecular dynamics simulation of ADP and acetyl phosphate Source: Aaron Halpern, UCL (CC-BY 4.0)

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

Combining these results with molecular dynamics modeling, the authors propose a mechanistic explanation for the specificity of the ADP/AcP/iron reaction by hypothesizing that the small diameter and high charge density of the iron ion formed in combination with the conformation of the intermediate become when the three come together, providing a “just right” geometry that allows AcP’s phosphate to switch partners and form ATP.

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