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Tuesday, 4 October 2022

Creationism In Crisis - Another 'God-Filled' Gap Just Got a Lot Smaller

Molecular dynamic simulation of ADP and acetyl phosphate

Aaron Halpern, UCL (CC-BY 4.0)

What is perhaps the favourite of all Creationism's 'God-filled' gaps - abiogenesis - just go a lot smaller with the news today that Nick Lane and colleagues of University College, London, UK, have shown how ATP became the universal energy currency used by all living organisms, so adding another layer to our understanding of how the earliest self-sufficient, self-replicating organisms arose from pre-existing molecules.

As always, the process evicts Creationism's shrinking little god because it is explained using just the natural laws of chemistry and physics acting on pre-existing molecules, with no place for magic or supernatural powers.

The mystery was, how the system for producing ATP could have evolved when the process used by cells today is a multi-step process which itself utilises ATP at six different points. Clearly, there must have been a simpler process for creating ATP early on in the evolution of living organisms and, because of it's universality, this was almost certainly in a common ancestor to all forms of life.

In prokaryote cells such as bacteria, the process occurs in the cell itself but in eukaryote cells the process takes place in the mitochondria - the descendants of bacteria originally incorporated into other prokaryote cells to give rise to the eukaryotes.
What is ATP and how is it synthesised? Wikipedia - Adenosine triphosphate
As explained in information provided ahead of publication by PLoS Biology:
Ancient chemistry may explain why living things use ATP as the universal energy currency

An early step in metabolic evolution set the stage for emergence of ATP as the universal energy carrier

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 October 4th in the open access journal PLOS Biology, by Nick Lane and colleagues of University College London, UK. The finding potentially sheds light on the earliest stages of prebiotic biochemistry, and suggests how ATP came to be 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 building ATP’s complex chemical structure from scratch is energy intensive and requires six separate ATP-driven steps; while convincing models do allow for prebiotic formation of the ATP skeleton without energy from already-formed ATP, they also suggest ATP was likely quite scarce, and that some other 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 functions today in both bacteria and archaea as a metabolic intermediate. AcP has been shown to phosphorylate ADP to ATP in water in the presence of iron ions, but a host of questions remained after that demonstration, including whether other small molecules might work as well, whether AcP is specific for ADP or instead could function 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.

In their new study, the authors explored all these questions. Drawing on data and hypotheses about the chemical conditions of the Earth 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 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 accepted a phosphate from AcP.

Combining these results with molecular-dynamic modeling, the authors propose a mechanistic explanation for the specificity of the ADP/AcP/iron reaction, hypothesizing 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, provide 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, 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.

Nick Lane, senior author
Centre for Life’s Origins and Evolution (CLOE)
Department of Genetics, Evolution and Environment
University College London, London, UK.

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.

Silvana Pinna, lead author
Centre for Life’s Origins and Evolution (CLOE)
Department of Genetics, Evolution and Environment
University College London, London, UK.
The scientists give more details in the abstract to their open access paper in PLoS Biology:
Abstract

ATP is universally conserved as the principal energy currency in cells, driving metabolism through phosphorylation and condensation reactions. Such deep conservation suggests that ATP arose at an early stage of biochemical evolution. Yet purine synthesis requires 6 phosphorylation steps linked to ATP hydrolysis. This autocatalytic requirement for ATP to synthesize ATP implies the need for an earlier prebiotic ATP equivalent, which could drive protometabolism before purine synthesis. Why this early phosphorylating agent was replaced, and specifically with ATP rather than other nucleoside triphosphates, remains a mystery. Here, we show that the deep conservation of ATP might reflect its prebiotic chemistry in relation to another universally conserved intermediate, acetyl phosphate (AcP), which bridges between thioester and phosphate metabolism by linking acetyl CoA to the substrate-level phosphorylation of ADP. We confirm earlier results showing that AcP can phosphorylate ADP to ATP at nearly 20% yield in water in the presence of Fe3+ ions. We then show that Fe3+ and AcP are surprisingly favoured. A wide range of prebiotically relevant ions and minerals failed to catalyse ADP phosphorylation. From a panel of prebiotic phosphorylating agents, only AcP, and to a lesser extent carbamoyl phosphate, showed any significant phosphorylating potential. Critically, AcP did not phosphorylate any other nucleoside diphosphate. We use these data, reaction kinetics, and molecular dynamic simulations to infer a possible mechanism. Our findings might suggest that the reason ATP is universally conserved across life is that its formation is chemically favoured in aqueous solution under mild prebiotic conditions.

Pinna S, Kunz C, Halpern A, Harrison SA, Jordan SF, Ward J, et al. (2022)
A prebiotic basis for ATP as the universal energy currency.
PLoS Biol 20(10): e3001437. DOI: 10.1371/journal.pbio.3001437

Copyright: © 2022 The authors.
Published by PLoS. Open access
Reprinted under a Creative Commons Attribution 4.0 International license (CC BY 4.0)
In summary then, a simple process involving nothing more that the chemicals already present on Earth and the laws of chemistry and physics, can account for how a bacterium could have had a supply of ATP before the now universal process whereby the energy in a molecule of glucose is used to built several molecules of ATP from ADP and phosphate. ATP was then available to be incorporated into other evolving metabolic processes, including that which now produce more ATP that it consumes, more efficiently that the simple process which could then be abandoned by evolution.

This bacterium, or one of its descendants became incorporated into what was to become the cells that all multicellular and very many single-cells organisms are now composed of - and Creationism's 'abiogenesis gap' just got filled with another shovel full of scientific facts.

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