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Cited by 90Phytase and its ApplicationsSphingolipid Metabolism and SignalingProtein Kinase Regulation and GTPase Signaling

Do Mammals Make All Their Own Inositol Hexakisphosphate?

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Letcher, Andrew J., Schell, Michael J., Irvine, Robin F.·2008·Biochemical Journal
DOI 10.1042/bj20081417PMC PMC2605958
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Abstract

A highly specific and sensitive mass assay for inositol hexakisphosphate (InsP6) was characterized. This centres around phosphorylating InsP6 with [32P]ATP using a recombinant InsP6 kinase from Giardia lambia, followed by HPLC of the 32P-labelled products with an internal [3H]InsP7 standard. This assay was used to quantify InsP6 levels in a variety of biological samples. Concentrations of InsP6 in rat tissues varied from 10–20 μM (assuming 64% of wet weight of tissue is cytosol water), whereas using the same assumption axenic Dictyostelium discoideum cells contained 352±11 μM InsP6. HeLa cells were seeded at low density and grown to confluence, at which point they contained InsP6 levels per mg of protein similar to rat tissues. This amounted to 1.952±0.117 nmol InsP6 per culture dish, despite the cells being grown in serum shown to contain no detectable (less than 20 pmol per dish) InsP6. These results demonstrate that mammalian cells synthesize all their own InsP6. Human blood was analysed, and although the white cell fraction contained InsP6 at a concentration comparable with other tissues, in serum and platelet-free plasma no InsP6 was detected (<1 nM InsP6). Human urine was also examined, and also contained no detectable (<5 nM) InsP6. These results suggest that dietary studies purporting to measure InsP6 at micromolar concentrations in human plasma or urine may not have been quantifying this inositol phosphate. Therefore claims that administrating InsP6 in the diet or applying it topically can produce health benefits by increasing extracellular InsP6 levels may require reassessment.

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  • In mammalian cells, InsP5 and InsP6 are produced in significantly higher concentrations compared to other inositol phosphates.

    “In mammalian cells, InsP5 and InsP6 are produced in significantly higher concentrations compared to other inositol phosphates [39,40], representing the highest products in the HOIP pathway.”

    From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [39]

    The Results (Table 1; page not provided) quantify InsP6 in rat tissues and HeLa cells, and the Introduction describes InsP5 as an intermediate in InsP6 synthesis. The paper does not establish that either compound is present at significantly higher concentrations than other inositol phosphates; its Discussion says the assay was not designed to quantify lower inositol phosphates. (LLM, conf=0.88)

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Cited by

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Authors
Letcher, A. J., Schell, M. J., & Irvine, R. F.
Affiliations
University of Cambridge (GB)
Corresponding author
Irvine, Robin F.
ORCID
Schell, Michael J.
Venue
Biochemical Journal
Publisher
Portland Press Ltd.
Published
2008-11-12
Volume
416
Issue
2
Pages
263-270
ISSN
  • 0264-6021 (ISSN-L)
  • 1470-8728
DOI
10.1042/bj20081417
PMC
PMC2605958
OpenAlex
W2048806742
Cited by
90
References
2
Citations by year
2026: 2 · 2025: 7 · 2024: 5 · 2023: 6 · 2022: 8 · 2021: 7 · 2020: 9 · 2019: 4 · 2018: 5 · 2017: 2 · 2016: 3 · 2015: 5 · 2014: 5 · 2013: 3 · 2012: 4
FWCI
6.06
Type
journal article
Language
en
Open access
Licence
Locations
  • Biochemical Journal (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
  • Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion, other-oa)
Funders
  • Wellcome Trust
  • Royal Society
Topics
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Phytase and its Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
phytic acid, mammalian cells, mass spectrometry assay, HeLa cells, Dictyostelium discoideum, human blood, serum, urine, inositol phosphates
MeSH terms
Animals, Brain, Cattle, Chromatography, High Pressure Liquid, Dictyostelium, HeLa Cells, Humans, Inositol Phosphates, Lung, Mammals, Phytic Acid, Rats

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