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Cited by 1,867Biochemical and Molecular ResearchCancer and biochemical researchDNA and Nucleic Acid Chemistry

Physiological concentrations of purines and pyrimidines

Traut, Thomas W.·1994·Molecular and Cellular Biochemistry
DOI 10.1007/bf00928361
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Abstract

The concentrations of bases, nucleosides, and nucleosides mono-, di- and tri-phosphate are compared for about 600 published values. The data are predominantly from mammalian cells and fluids. For the most important ribonucleotides, average concentrations +/- SD (microM) are: ATP, 3,152 +/- 1,698; GTP, 468 +/- 224; UTP, 567 +/- 460 and CTP, 278 +/- 242. For deoxynucleosides-triphosphate (dNTP), the concentrations in dividing cells are: dATP, 24 +/- 22; dGTP, 5.2 +/- 4.5; dCTP, 29 +/- 19 and dTTP 37 +/- 30. By comparison, dUTP is usually about 0.2 microM. For the 4 dNTPs, tumor cells have concentrations of 6-11 fold over normal cells, and for the 4 NTPs, tumor cells also have concentrations 1.2-5 fold over the normal cells. By comparison, the concentrations of NTPs are significantly lower in various types of blood cells. The average concentration of bases and nucleosides in plasma and other extracellular fluids is generally in the range of 0.4-6 microM; these values are usually lower than corresponding intracellular concentrations. For phosphate compounds, average cellular concentrations are: Pi, 4400; ribose-1-P, 55; ribose-5-P, 70 and P-ribose-PP, 9.0. The metal ion magnesium, important for coordinating phosphates in nucleotides, has values (mM) of: free Mg2+, 1.1; complexed-Mg, 8.0. Consideration of experiments on the intracellular compartmentation of nucleotides shows support for this process between the cytoplasm and mitochondria, but not between the cytoplasm and the nucleus.

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  • Circulating nucleotide concentrations are likely too low for many tumors to satisfy their nucleotide demand through salvage alone.

    “Though nucleotide salvage pathways can support tumor cell proliferation in certain contexts (Tabata et al., 2017), concentrations of circulating nucleotides are likely too low for many tumors to satisfy their nucleotides demand via salvage alone (Traut, 1994).”

    From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Traut, 1994

  • Upon G12 and G13 mutation, GAP-mediated K-Ras inactivation is hampered, resulting in accumulation of GTP-bound active K-Ras.

    “Upon G12 and G13 mutation, GAPs-mediated K-Ras inactivation is hampered, resulting in the accumulation of GTP-bound active K-Ras.24,39”

    From Overcoming Resistance to Drugs Targeting KRAS Mutation (2020) · cites this paper as [24]

  • The difficulty of drugging KRAS reflects picomolar RAS affinity for GTP, high intracellular GTP concentration of about 500 nM, and the absence of a deep or pharmacologically actionable small-molecule-binding pocket; GTP-competitive RAS inhibitors are therefore unfeasible.

    “The several-decade struggle to drug KRAS and other RAS isoforms25,61 reflects challenges posed by three key biochemical features: first, the picomolar affinity of RAS proteins for GTP62; second, the high intracellular concentrations of GTP (~500 nM)9; and third, the absence of a deep or pharmacologically actionable small-molecule-binding pocket in the RAS proteins.”

    From The current state of the art and future trends in RAS-targeted cancer therapies (2022) · cites this paper as [9]

  • Because the cellular GTP:GDP ratio is about 10, RAS-GEFs catalyse GDP-to-GTP exchange in cells.

    “RAS-GEFs can promote the release of either GDP or GTP from RAS proteins in vitro; however, because the cellular GTP:GDP ratio is ~10 (refs.8,9), they catalyse GDP-to-GTP exchange in cells.”

    From The current state of the art and future trends in RAS-targeted cancer therapies (2022) · cites this paper as [9]

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Authors
Traut, T. W.
Affiliations
University of North Carolina at Chapel Hill (US)
Corresponding author
Traut, Thomas W.
ORCID
Traut, Thomas W.
Venue
Molecular and Cellular Biochemistry
Publisher
Springer Science and Business Media LLC
Published
1994
Volume
140
Issue
1
Pages
1-22
ISSN
  • 0300-8177 (ISSN-L)
  • 1573-4919
DOI
10.1007/bf00928361
OpenAlex
W2045074917
Cited by
1,867
References
108
Citations by year
2026: 78 · 2025: 120 · 2024: 113 · 2023: 124 · 2022: 123 · 2021: 97 · 2020: 129 · 2019: 107 · 2018: 85 · 2017: 91 · 2016: 80 · 2015: 55 · 2014: 70 · 2013: 55 · 2012: 53
FWCI
0.80
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • Molecular and Cellular Biochemistry (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
Keywords
purines, pyrimidines, nucleotide concentration, nucleosides, ribonucleotides, deoxynucleotides, ATP, GTP, UTP, CTP, dNTPs, extracellular nucleotides, cancer cells, blood cells, intracellular phosphate, ribose-1-phosphate, ribose-5-phosphate, magnesium
MeSH terms
Animals, Cells, Cells, Cultured, Extracellular Space, Humans, Neoplasms, Nucleosides, Nucleotides, Purines, Pyrimidines

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