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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Wang, B., Miao, Z., & Chen, R. (2007) · Heteroatom Chemistry · doi:10.1002/hc.20306 · Cited by 13
Partitioning of phosphorus between biochemical and storage compounds in leaves follows a consistent pattern across four Australian genera growing in native settings
McQuillan, M., Smernik, R. J., & Doolette, A. L. (2020) · Plant and Soil · doi:10.1007/s11104-020-04567-4 · Cited by 13
“Life would not be possible without it due to its intrinsic chemical characteristics, which make it indispensable in key biochemicals and biochemical reactions (Westheimer 1987; Smil 2000).”
Background
18O Isotope Labeling Combined with 31P Nuclear Magnetic Resonance Spectroscopy for Accurate Quantification of Hydrolyzable Phosphorus Species in Environmental Samples
Wang, L., Amelung, W., & Willbold, S. (2021) · Analytical Chemistry · doi:10.1021/acs.analchem.0c03379 · Cited by 13
ATP induces folding of ALS-causing C71G-hPFN1 and nascent hSOD1
Kang, J., Lim, L., & Song, J. (2023) · Communications Chemistry · doi:10.1038/s42004-023-00997-0 · Cited by 13
Sequence – dynamics – function relationships in protein tyrosine phosphatases
Crean, R. M., Corbella, M., Calixto, A. R., Hengge, A. C., & Kamerlin, S. C. L. (2024) · QRB Discovery · doi:10.1017/qrd.2024.3 · Cited by 12
“…phosphatase 1B (PTP1B), as well as the Yersinia virulence factor YopH ( ‘ Yersinia outer protein H ’ ), two of the most studied PTPs to date (e.g., Westheimer, 1987; Tonks et al., 1988; Zhang et al., 1992; Zhang and Dixon, 1994; Hunter, 1995, 2000; Johnson et al., 2002; Zhang, 2002; Haj et…”
Background
Multicomponent reactions in a one-pot synthesis of α-aminophosphonates and α-aminophosphonic diamides with anti-inflammatory properties
Abdou, W. M., Barghash, R. F., & Bekheit, M. S. (2011) · Monatshefte für Chemie - Chemical Monthly · doi:10.1007/s00706-011-0492-8 · Cited by 13
Calculated Spectroscopy and Atmospheric Photodissociation of Phosphoric Acid
Yekutiel, M., Lane, J. R., Gupta, P., et al. (2010) · The Journal of Physical Chemistry A · doi:10.1021/jp1007957 · Cited by 13
Prebiological Evolution and the Metabolic Origins of Life
Pratt, A. J. (2011) · Artificial Life · doi:10.1162/artl_a_00032 · Cited by 13
“ATP is the archetypal water compatible dehydrating agent [ 79 ].,Once available, phosphates brought important opportunities to biochemical systems [ 79 ].,The ability of phosphate to link two units and retain a negative charge is critical to the structure and function of nucleic acids [ 79 ].”
Background
Reactivity of Metaphosphate and Thiometaphosphate in Water: A DFT Study
Zhang, L., Xie, D., Xu, D., et al. (2005) · The Journal of Physical Chemistry A · doi:10.1021/jp054430t · Cited by 13
Enzymatic phosphorylation of hair keratin enhances fast adsorption of cationic moieties
Volkov, V., & Cavaco-Paulo, A. M. (2016) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2015.12.082 · Cited by 13
Study of the Phosphoryl‐Transfer Mechanism of Shikimate Kinase by NMR Spectroscopy
Prado, V., Lence, E., Vallejo, J. A., Beceiro, A., Thompson, P., Hawkins, A. R., & González‐Bello, C. (2016) · Chemistry - A European Journal · doi:10.1002/chem.201504438 · Cited by 13
Rewarming the Primordial Soup: Revisitations and Rediscoveries in Prebiotic Chemistry
Saladino, R., Šponer, J. E., Šponer, J., & Mauro, E. D. (2017) · ChemBioChem · doi:10.1002/cbic.201700534 · Cited by 11
Differences in the relationship between metabolomic and ionomic traits of Quercus variabilis growing at contrasting geologic-phosphorus sites in subtropics
Ji, H., Ossipov, V. I., Du, B., et al. (2019) · Plant and Soil · doi:10.1007/s11104-019-04020-1 · Cited by 13
“Phosphorus comprises one of the primary life elements that is involved in a variety of biochemical processes, and is essential for the synthesis of many key compounds including nucleic acids, membrane lipids, etc. (Amtmann and Armengaud 2009; Westheimer 1987).”
Background
Catalytic Enantioselective Synthesis of Aryl–Methyl Organophosphorus Compounds
Yadav, A. A., Kumar, D., Mishra, M. K., et al. (2021) · The Journal of Organic Chemistry · doi:10.1021/acs.joc.0c02675 · Cited by 13
Organophotocatalysis Enables the Synthesis of gem-Fluorophosphonate Alkenes
Morand, S., Lecroq, W., Jubault, P., et al. (2022) · Organic Letters · doi:10.1021/acs.orglett.2c03366 · Cited by 13
Mechanism of PhosphoThreonine/Serine Recognition and Specificity for Modular Domains from All-atom Molecular Dynamics
Huang, Y. M., & Chang, C. A. (2011) · BMC Biophysics · doi:10.1186/2046-1682-4-12 · Cited by 13
A Theoretical Study of the Chorismate Synthase Reaction
Dmitrenko, O., Wood, H. B., Bach, R. D., et al. (2001) · Organic Letters · doi:10.1021/ol0167964 · Cited by 13
Biocatalytic Phosphorylation of Metabolites
Gauss, D., Schönenberger, B., Molla, G. S., et al. (2016) · doi:10.1002/9783527677122.ch8 · Cited by 13
Soil Microbial Community Succession Based on PhoD and Gcd Genes along a Chronosequence of Sand-Fixation Forest
Wang, F., Zhang, Y., Xia, Y., et al. (2021) · Forests · doi:10.3390/f12121707 · Cited by 12
“P is an essential macronutrient for all living cells and is vital to the survival of plant and soil microbes [1] Although various forms of P are relatively abundant in soils, it is usually considered as one of the limiting nutrients for plants and soil microorganisms because most P cannot be directly utilized [2].”
Background
Thermal Conversion of Sodium Phytate Using the Oxygen Carrier Ilmenite Interaction with Na-Phosphate and Its Effect on Reactivity
Olsson, E. O. L., Purnomo, V., Glarborg, P., et al. (2022) · Energy & Fuels · doi:10.1021/acs.energyfuels.2c00967 · Cited by 12
Causal impact analysis of enhanced phosphorus effluent standard on river water quality
Kim, S., & Chung, S. (2022) · Journal of Environmental Management · doi:10.1016/j.jenvman.2022.115931 · Cited by 12
Phosphorus speciation and colloidal phosphorus responses to short-term cessation of fertilization in a lime concretion black soil
Shanshan, B. A. I., Tan, J., ZHANG, Z., et al. (2023) · Pedosphere · doi:10.1016/j.pedsph.2023.01.004 · Cited by 12
Inorganic Bottlebrush and Comb Polymers as a Platform for Supersoft, Solvent-Free Elastomers
Ajvazi, E., Bauer, F., Strasser, P., Brüggemann, O., Preuer, R., Kráčalík, M., Hild, S., Abbasi, M., Graz, I. M., & Teasdale, I. (2024) · ACS Polymers Au · doi:10.1021/acspolymersau.3c00043 · Cited by 12
Integrated physiological, transcriptomic and metabolomic analyses provide insights into phosphorus-mediated cadmium detoxification in Salix caprea roots
Li, A., Wang, Y., Li, X., et al. (2024) · Plant Physiology and Biochemistry · doi:10.1016/j.plaphy.2024.108677 · Cited by 12
Evolution of phosphate scouting in the terrestrial biosphere
Abel, S., & Naumann, C. (2024) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2023.0355 · Cited by 13
“…which assigns P at its predominant pentavalent oxidation state on Earth, orthophosphate (PO 4 3− ) or inorganic phosphate (Pi), a central place in biology, and empowers conjugate phosphate esters and phosphoric anhydrides to assume universal functions in cellular and organismal biochemistry [2,3].”
Background

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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