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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“A major reason why nature has chosen phosphate for so many purposes in living systems is that it can link up to two adjacent groups, like in nucleic acids, and still remain ionized (Westheimer, 1987).”
Background
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“As for the inorganic moiety of the constant part of the nucleic genetic polymer, it was convincingly argued [46] that there are few possible alternatives to phosphate and that elements like vanadium, silicium and sulfur do not seem to be valid substitutes [16].”
Background
Origins of Life: The Primal Self-Organization
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“…is an exception that has been discussed in a reference article where the remarkable role of phosphate for life is accurately highlighted (Westheimer 1987): phosphate-containing molecules are critical for life because life develops in water under conditions where phosphate bond…”
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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