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Why Living Things Use ATP As the Universal Energy Currency

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Simple two-carbon compounds may have played a key role in the evolution of metabolism before cells emerged, according to new research.

Early stages of metabolic evolution set the stage for the emergence of ATP as a universal energy carrier.

Simple two-carbon compounds may have played important roles in the evolution of metabolism before the emergence of cells. This is according to new research by Nick his Lane and his colleagues at University College England, London, published in an open access journal. PLOSbiology October 4thThis finding may provide important insight into the early stages of prebiotic biochemistry. Furthermore, the findings suggest how ATP (adenosine triphosphate) became a universal energy carrier for all cellular life today.

Adenosine triphosphate (ATP) is an organic compound that provides the energy that drives many processes in living cells, including nerve impulse propagation, muscle contraction, condensate dissolution, and chemosynthesis. ATP is found in all known life forms and is often referred to as the “molecular unit of currency” for intracellular energy transfer.

ATP is used by all cells as an energy intermediate. During cellular respiration, energy is captured when phosphate is added to ADP (adenosine diphosphate) to generate ATP. The cleavage of that phosphate releases energy, powering 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. A compelling model allows prebiotic formation of the ATP scaffold without energy from already formed ATP, but also indicates that ATP is likely to be very scarce. This means that other compounds may have played a central role in the conversion of ADP to ATP at this stage of evolution.

Lane et al. believed that the most likely candidate 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 ferric ions, but after that demonstration, we will investigate whether other small molecules function similarly and whether AcP is specific for ADP. Many questions remained, such as whether or not, or if it would work the same way instead. Whether iron is unique in its ability to bind well with the diphosphates of other nucleosides (such as guanosine and cytosine) and catalyze ADP phosphorylation in water.

Molecular dynamics simulation of ADP and acetyl phosphate

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

The authors explored all these questions in a new study. They used data and hypotheses about the chemical state of the pre-life Earth to test the ability of other ions and minerals to catalyze ATP formation in water. Nothing was more effective than iron. Next, they tested a panel of other small organic molecules for their ability to phosphorylate ADP. None was as effective as AcP and only one other he (carbamoyl phosphate) showed significant activity. Finally, we showed that none of the other nucleoside diphosphates accept the phosphate from AcP.

Combining these results with molecular dynamics modeling, the authors propose a mechanistic explanation for the peculiarities of the ADP/AcP/iron reaction, in which the small diameter and high charge density of the iron ions are responsible for the intermediates formed. It is hypothesized that it is combined with the conformation of Together the three provide a “just right” shape that allows the phosphate of AcP to switch partners to form ATP.

“Our results suggest that AcP is the most plausible precursor for ATP as a biological phosphorylator,” says Lane. From the unique interaction of ADP and AcP. Over time, with the advent of suitable catalysts, ATP eventually replaced AcP as the ubiquitous phosphate donor,[{” attribute=””>amino acids and nucleotides to form

Lead author Silvana Pinna adds, “ATP is so central to metabolism that I thought it might be possible to form it from ADP under prebiotic conditions. But I also thought that several phosphorylating agents and metal ion catalysts would work, especially those conserved in life. It was very surprising to discover the reaction is so selective – in the metal ion, phosphate donor, and substrate – with molecules that life still uses. The fact that this happens best in water under mild, life-compatible conditions is really quite significant for the origin of life.”

Reference: “A prebiotic basis for ATP as the universal energy currency” by Silvana Pinna, Cäcilia Kunz, Aaron Halpern, Stuart A. Harrison, Sean F. Jordan, John Ward, Finn Werner and Nick Lane, 4 October 2022, PLOS Biology.
DOI: 10.1371/journal.pbio.3001437

Funding: We are grateful to the Biotechnology and Biological Sciences Research Council to NL, FW and JW (BB/V003542/1) and HR (LIDo Doctoral Training Program), to Gates Ventures (formerly bgc3) to NL, and to the Natural Environment Research Council to AH and NL (2236041). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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