ATP is the Most Important Molecule of Life

ATP is the Most Important Molecule of Life

Authors: William Ehringer, Ph.D., Kristyn Smith MEng

Adenosine-5’-Triphosphate (or ATP) is the energy that fuels life. Simply put, without ATP all living things on planet Earth would cease to exist.

So how did ATP become so important and why is it necessary for life? Let’s start the explanation by tracing the origins of life and looking at the important roles ATP played. 

There are a several different theories on the origins of life (broken down by the major differing factors):

  • Autocatalysis vs. Replication, where the focus is on the main primitive functions. [1]
  • The primary location of first living systems. [1]
  • RNA vs. DNA, where the focus is on the first molecules involved in the origin of life. [1]

Our focus is on the latter, and the differences regarding the first molecules involved in the origins of life. The “RNA World” hypothesis was first proposed in the 1960’s by Stanley Miller by his experiment that showed that under similar conditions to primitive Earth, spontaneous production of amino acids and nucleotides was possible. [2] The opposing theory focuses on a primitive DNA-enzyme complex which was performed by replication via polymerases. [1] This differing hypothesis proposes that protein-like molecules were seen as better candidates than RNA to be the first functioning self-replicators. [1] Recently, Xu et al. proposed the “R/DNA World” theory where the first genetic system was made from both RNA and DNA nucleotides. [3]

While we can only hypothesize which is the true origins of primordial life, what we DO know is that all three of these hypotheses required a tremendous amount of energy to carry out the necessary chemical reactions, simply mixing the components in a water-based solution would not lead to spontaneous formation of the molecules. Moreover, where did the phosphorus in the nucleotides come from? The earth’s crust contains levels of phosphorus, but they are not readily soluble in water or only small amounts are released. [4]

Pasek et. A. showed that the corrosion of the meteorite-based mineral schreibersite ((Fe,Ni)3P) formed phosphite radicals in aqueous (or water-based) solutions. [5] These free radicals can then form activated polyphosphates which can be used as an energy source used to fuel the aforementioned biomolecules). [5, 10]

Figure 1 - Meteorite-based mineral Schreibersite. [16]

 

In order for the chemical reactions to occur with any efficiency, the individual components had to be brought together.  The leading hypothesis is that lipids and other hydrocarbons on the surface of the primordial oceans began to turn into vesicles due to wave action.  The chemical components were then trapped inside of the vesicles were they could interact and not be dispersed.  During this time period ATP was formed from an adenine, a ribose sugar and three phosphate groups and became the universal energy currency in cells. [6] By sequestering polyphosphates with the building blocks of RNA inside precursor cells, an internal energy source was now bioavailable for chemical synthesis. [6, 7]. The phosphates attached to the adenosine provided stored energy in the bonds between them, which can be used to power reactions, and the formation of new molecules.

Figure 2 – ATP Molecule building blocks and energy from phosphates [17]

 

The atmosphere of primordial Earth was dominated by methane, carbon dioxide, and nitrogen. [8, 10] Experiments have been performed to demonstrate that ancient bacteria could generate ATP. The proteobacterium Thiomicrospira denitrificans can take an energy from the oxidation of thiosulfate (S2O32−) by a series of reactions to create several reactants including ATP. [9] This is interesting for several reasons; this experiment demonstrates that the bacterium can generate ATP, and the utilization of an inorganic energy source via the Krebs Cycle lends credence to the bacterium’s ancient origins [9]. Eventually ancient bacteria on primordial Earth could generate ATP, but only small amounts could be made, hence life remained microscopic. However, over hundreds of millions of years, as photosynthetic organisms sprang to existence, oxygen (O2) appeared in the atmosphere (approximately 2.4 Gya, or 2.4x109 years ago). Organisms were forced to adapt, move to anaerobic regions, or become extinct. [10, 11]

Figure 3 – Evolution of Life and Photosynthetic Eukaryotes in Geological Context [10]

Eventually most organisms evolved to couple ATP generation to available oxygen levels (O2), and thus much larger numbers of ATP molecules were able to be made. [10] This not only allowed organisms to grow larger in size (as they could make more molecules and cells) but also expanded the complexity of the organisms’ metabolic processes. [10].  A prime example of growing larger due to more oxygen availability, and hence more ATP, are dinosaurs.  It is estimated that during the Jurassic period the oxygen concentration was around 30-35%, which allowed dinosaurs to grow to massive sizes [18]. 

As the development of more complex eukaryotes increased, the role of ATP became more complex [10]. ATP was critical for the construction of structural components for cells, and was used to make other proteins, lipids, DNA and RNA. As cells are constantly dividing and making new cells, large amounts of ATP was required for these processes. [12] ATP was especially important as increased oxygen levels led to the increase in animal size and thus required larger amounts of ATP. [10, 11]

Fast forward millions of years to today, where the roles of ATP are multifaceted and well known. ATP is still vital to the production of proteins, lipids, DNA, and RNA. ATP is critical for cellular metabolism, providing the energy necessary and at a rate that is consistent with the rigorous demands of life. [13] ATP is integral for the transportation of ions into and out of the cell that allows cells to maintain an osmotic balance, without this delicate balance, cells would swell and burst. [13] ATP drives the important steps of muscle contraction, nerve transmission, and even functions as a cell signaling molecule. [13, 14, 15]

In summary, we now understand that nearly all functions of the body are dependent on a constant supply of ATP. From its origins in early Earth, to its continuing role in evolution, ATP is arguably one of the most important molecules for living beings.

References
[1] Demongeot, J., & Thellier, M. (2023). Primitive oligomeric RNAs at the origins of life on Earth. International Journal of Molecular Sciences, 24(3), 2274.
[2] Miller, S. L. (1953). A production of amino acids under possible primitive earth conditions. Science, 117(3046), 528-529.
[3] Xu, J., Green, N. J., Russell, D. A., Liu, Z., & Sutherland, J. D. (2021). Prebiotic photochemical coproduction of purine ribo-and deoxyribonucleosides. Journal of the American Chemical Society, 143(36), 14482-14486.
[4] Keefe, A. D., & Miller, S. L. (1995). Are polyphosphates or phosphate esters prebiotic reagents?. Journal of molecular evolution, 41, 693-702.
[5] Pasek, M. A., Dworkin, J. P., & Lauretta, D. S. (2007). A radical pathway for organic phosphorylation during schreibersite corrosion with implications for the origin of life. Geochimica et Cosmochimica Acta, 71(7), 1721-1736.
[6] Pinna, S., Kunz, C., Halpern, A., Harrison, S. A., Jordan, S. F., Ward, J., ... & Lane, N. (2022). A prebiotic basis for ATP as the universal energy currency. PLoS biology, 20(10), e3001437.
[7] Chu, X. Y., Xu, Y. Y., Tong, X. Y., Wang, G., & Zhang, H. Y. (2022). The legend of ATP: From origin of life to precision medicine. Metabolites, 12(5), 461.
[8] Kasting, J. F., Zahnle, K. J., Pinto, J. P., & Young, A. T. (1989). Sulfur, ultraviolet radiation, and the early evolution of life. Origins of Life and Evolution of the Biosphere, 19, 95-108.
[9] Fontecilla-Camps, J. C. (2021). Primordial bioenergy sources: The two facets of adenosine triphosphate. Journal of Inorganic Biochemistry, 216, 111347.
[10] Hohmann-Marriott, M. F., & Blankenship, R. E. (2011). Evolution of photosynthesis. Annual review of plant biology, 62, 515-548.
[11] Müller, M., Mentel, M., van Hellemond, J. J., Henze, K., Woehle, C., Gould, S. B., ... & Martin, W. F. (2012). Biochemistry and evolution of anaerobic energy metabolism in eukaryotes. Microbiology and Molecular Biology Reviews, 76(2), 444-495.
[12] Baum, D. A., & Baum, B. (2014). An inside-out origin for the eukaryotic cell. BMC biology, 12, 1-22.
[13] Nath, S. (2019). Integration of demand and supply sides in the ATP energy economics of cells. Biophysical Chemistry, 252, 106208.
[14] Hanson, R. W. (1989). The role of ATP in metabolism. Biochemical Education, 17(2), 86-92.
[15] Lee, E. E., O’Malley-Krohn, I., Edsinger, E., Wu, S., & Malamy, J. (2023). Epithelial wound healing in Clytia hemisphaerica provides insights into extracellular ATP signaling mechanisms and P2XR evolution. Scientific Reports, 13(1), 18819.
[16] Schreibersite: Mineral information, data and localities. Schreibersite. (n.d.). https://www.mindat.org/min-3582.html 
[17] Chapter 7: Concept 7.3: ATP Provides Energy for Cellular Work. (n.d.). https://bodell.mtchs.org/OnlineBio/BIOCD/text/chapter7/concept7.3.html 
[18] John G. Cramer Alternate View Column AV-27 Keywords: cretaceous, air, oxygen, amber, quetzalcotalus, pterosaur Published in the July-1988 issue of Analog Science Fiction & Fact Magazine
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