Cited by 1,711Physical Organic Chemistry and Reaction KineticsOrganophosphorus compounds synthesisOrigins and Evolution of Life

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Why Nature Chose Phosphates

Westheimer, F. H.·1987·Science

DOI 10.1126/science.2434996

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Abstract

Phosphate esters and anhydrides dominate the living world but are seldom used as intermediates by organic chemists. Phosphoric acid is specially adapted for its role in nucleic acids because it can link two nucleotides and still ionize; the resulting negative charge serves both to stabilize the diesters against hydrolysis and to retain the molecules within a lipid membrane. A similar explanation for stability and retention also holds for phosphates that are intermediary metabolites and for phosphates that serve as energy sources. Phosphates with multiple negative charges can react by way of the monomeric metaphosphate ion PO 3 - as an intermediate. No other residue appears to fulfill the multiple roles of phosphate in biochemistry. Stable, negatively charged phosphates react under catalysis by enzymes; organic chemists, who can only rarely use enzymatic catalysis for their reactions, need more highly reactive intermediates than phosphates.

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Frey, P. A. (1989) · Advances in enzymology and related areas of molecular biology/Advances in enzymology and related subjects · doi:10.1002/9780470123089.ch4 · Cited by 51
Ätiologie potentiell primordialer Biomolekül‐Strukturen: Vom Vitamin B12zu den Nukleinsäuren und der Frage nach der Chemie der Entstehung des Lebens – ein Rückblick
Eschenmoser, A. (2011) · Angewandte Chemie · doi:10.1002/ange.201103672 · Cited by 50
Nucleoside Phosphorylation: A Feasible Step in the Prebiotic Pathway to RNA
Reimann, R., & Zubay, G. (1999) · Origins of Life and Evolution of Biospheres · doi:10.1023/a:1006580009791 · Cited by 50
Suspended phosphorus sustains algal blooms in a dissolved phosphorus-depleted lake
Jin, Z., Liao, P., Jaisi, D. P., Wang, D., Wang, J., Wang, H., Jiang, S., Yang, J., Qiu, S., & Chen, J. (2023) · Water Research · doi:10.1016/j.watres.2023.120134 · Cited by 49
“Here, we combined solution P-31 nuclear magnetic resonance (31P NMR), sequential extraction, enzymatic hydrolysis, and 16S rRNA measurements to characterize speciation and biogeochemical cycling of P in Lake Erhai, China.”
BackgroundInfluential
Cyclophane Capsule Motifs with Side Pockets
Kang, S. O., Day, V. W., & Bowman‐James, K. (2008) · Organic Letters · doi:10.1021/ol800762j · Cited by 49
Metal-promoted hydrolysis of bis(p-nitrophenyl)phosphate by trivalent manganese complexes with Schiff base ligands in Gemini micellar solution
Jiang, W., Xu, B., Lin, Q., et al. (2007) · Colloids and Surfaces A Physicochemical and Engineering Aspects · doi:10.1016/j.colsurfa.2007.07.018 · Cited by 49
Multinuclear Diffusion NMR Spectroscopy and DFT Modeling: A Powerful Combination for Unraveling the Mechanism of Phosphoester Bond Hydrolysis Catalyzed by Metal‐Substituted Polyoxometalates
Lương, T. K. N., Shestakova, P. S., Mihaylov, T. T., et al. (2015) · Chemistry - A European Journal · doi:10.1002/chem.201405810 · Cited by 49
Promiscuity in the Enzymatic Catalysis of Phosphate and Sulfate Transfer
Pabis, A., Duarte, F., & Kamerlin, S. C. L. (2016) · Biochemistry · doi:10.1021/acs.biochem.6b00297 · Cited by 50
Synthesis of Modified Nucleoside Oligophosphates Simplified: Fast, Pure, and Protecting Group Free
Singh, J., Ripp, A., Haas, T., Qiu, D., Keller, M., Wender, P. A., Siegel, J. S., Baldridge, K. K., & Jessen, H. J. (2019) · Journal of the American Chemical Society · doi:10.1021/jacs.9b08273 · Cited by 49
Synthesis and DNA Cleavage Activity of Artificial Receptor 1,4,7-Triazacyclononane Containing Guanidinoethyl and Hydroxyethyl Side Arms
Sheng, X., Lu, X., Zhang, J., Chen, Y.-T., Lu, G., Shao, Y., Liu, F., & Xu, Q. (2007) · The Journal of Organic Chemistry · doi:10.1021/jo0624041 · Cited by 49
Self-Assembly of Phosphate Amphiphiles in Mixtures of Prebiotically Plausible Surfactants
Albertsen, A. N., Duffy, C. D., Sutherland, J. D., & Monnard, P. (2014) · Astrobiology · doi:10.1089/ast.2013.1111 · Cited by 49
“Phosphates are today present ubiquitously in the cell as components of nucleic acid backbones, lipids, and other metabolites (Westheimer, 1987), as well as in energy currency molecules.”
Hydrolysis of Phosphate Esters Catalyzed by Inorganic Iron Oxide Nanoparticles Acting as Biocatalysts
Huang, X. (2018) · Astrobiology · doi:10.1089/ast.2016.1628 · Cited by 50
“Hydrolysis of organic phosphate ester is related to the formation and function of the most important two biopolymers of life: (i) RNA and DNA, which encode genetic information (Westheimer, 1987), and (ii) protein that is related to the reversible phosphorylation (Hunter, 2012).”
Simultaneous release of polyphosphate and iron-phosphate from waste activated sludge by anaerobic fermentation combined with sulfate reduction
Hu, P., Liu, J., Wu, L., et al. (2018) · Bioresource Technology · doi:10.1016/j.biortech.2018.09.117 · Cited by 48
Conformational Changes in Four Regions of the Escherichia coli ArsA ATPase Link ATP Hydrolysis to Ion Translocation
Zhou, T., Radaev, S., Rosen, B. P., & Gatti, D. L. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m103671200 · Cited by 48
Were the first organisms heat engines? A new model for biogenesis and the early evolution of biological energy conversion
Muller, A. W. J. (1995) · Progress in Biophysics and Molecular Biology · doi:10.1016/0079-6107(95)00004-7 · Cited by 48
A Supramolecular Sensor Array Using Lanthanide-Doped Nanoparticles for Sensitive Detection of Glyphosate and Proteins
Wang, M., Ye, H., You, L., et al. (2015) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.5b09607 · Cited by 47
On the Origin of Phosphorylated Biomolecules
Pasek, M. A., & Kee, T. P. (2011) · Springer eBooks · doi:10.1007/978-3-642-21625-1_3 · Cited by 51
Reactivity of Phosphate Monoester Monoanions in Aqueous Solution. 1. Quantum Mechanical Calculations Support the Existence of “Anionic Zwitterion” MeO+(H)PO32- as a Key Intermediate in the Dissociative Hydrolysis of the Methyl Phosphate Anion1
Bianciotto, M., Barthelat, J.-C., & Vigroux, A. (2002) · Journal of the American Chemical Society · doi:10.1021/ja0200948 · Cited by 47
Metal Dependence of Transcriptional Switching in Escherichia coli Ada
Myers, L. C., Jackow, F., & Verdine, G. L. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.12.6664 · Cited by 47
Serpentinization as a route to liberating phosphorus on habitable worlds
Pasek, M. A., Omran, A., Feng, T., Gull, M., Lang, C., Abbatiello, J., Garong, L., Johnston, R., Ryan, J., & Abbott-Lyon, H. (2022) · Geochimica et Cosmochimica Acta · doi:10.1016/j.gca.2022.09.027 · Cited by 50
Microfluidic Production of Pyrophosphate Catalyzed by Mineral Membranes with Steep pH Gradients
Wang, Q., Barge, L. M., & Steinbock, O. (2019) · Chemistry - A European Journal · doi:10.1002/chem.201805950 · Cited by 46
A physicochemical orthophosphate cycle via a kinetically stable thermodynamically activated intermediate enables mild prebiotic phosphorylations
Maguire, O. R., Smokers, I. B. A., & Huck, W. T. S. (2021) · Nature Communications · doi:10.1038/s41467-021-25555-x · Cited by 47

Authors: Westheimer, F. H.
Affiliations: Harvard University (US)
Corresponding author: Westheimer, F. H.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 1987-03-06
Volume: 235
Issue: 4793
Pages: 1173-1178
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.2434996
OpenAlex: W2064761203
Semantic Scholar: 5ca074c6259fad7d448fb8587c394e507dd3ee19
Cited by: 1,711
References: 60
Citations by year: 2026: 68 · 2025: 75 · 2024: 96 · 2023: 89 · 2022: 90 · 2021: 80 · 2020: 77 · 2019: 71 · 2018: 68 · 2017: 71 · 2016: 54 · 2015: 84 · 2014: 69 · 2013: 62 · 2012: 65
FWCI: 14.06
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Topics: Physical Sciences › Chemistry › Organic Chemistry › Physical Organic Chemistry and Reaction Kinetics
Physical Sciences › Chemistry › Organic Chemistry › Organophosphorus compounds synthesis
Physical Sciences › Physics and Astronomy › Astronomy and Astrophysics › Origins and Evolution of Life
Keywords: phosphate, phosphoric acid, nucleic acids, energy storage, enzyme catalysis
MeSH terms: Amides, Animals, Arsenates, Chemistry, Citrates, Electrochemistry, Humans, Hydrolysis, Ions, Nucleic Acids, Phosphates, RNA, Silicic Acid, Citric Acid, Chemical Phenomena

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