Kim, Geun-Don;
Liu, Guizhen;
Qiu, Danye;
De Leo, Maria Giovanna;
Gopaldass, Navin;
Hermes, Jacques;
Timmer, Jens;
... Jessen, Henning Jacob; + view all
(2025)
Pools of Independently Cycling Inositol Phosphates Revealed by
Pulse Labeling with 18 O‑Water.
Journal of the American Chemical Society
, 147
(21)
pp. 17626-17641.
10.1021/jacs.4c16206.
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Abstract
Inositol phosphates control many central processes in eukaryotic cells including nutrient availability, growth, and motility. Kinetic resolution of a key modulator of their signaling functions, the turnover of the phosphate groups on the inositol ring, has been hampered by slow uptake, high dilution, and constraining growth conditions in radioactive pulse-labeling approaches. Here, we demonstrate a rapid (seconds to minutes) and nonradioactive labeling strategy of inositol polyphosphates through 18 O-water in yeast, human cells, and amoeba, which can be applied in any media. In combination with capillary electrophoresis and mass spectrometry, 18O-water labeling simultaneously dissects the in vivo phosphate group dynamics of a broad spectrum of even rare inositol phosphates. The good temporal resolution allowed us to discover vigorous phosphate group exchanges in some inositol polyphosphates and pyrophosphates, whereas others remain remarkably inert. We propose a model in which the biosynthetic pathway of inositol polyphosphates and pyrophosphates is organized in distinct, kinetically separated pools. While transfer of compounds between those pools is slow, each pool undergoes rapid internal phosphate cycling. This might enable the pools to perform distinct signaling functions while being metabolically connected.
| Type: | Article |
|---|---|
| Title: | Pools of Independently Cycling Inositol Phosphates Revealed by Pulse Labeling with 18 O‑Water |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1021/jacs.4c16206 |
| Publisher version: | https://doi.org/10.1021/jacs.4c16206 |
| Language: | English |
| Additional information: | Copyright © 2025 The Authors. Published by American Chemical Society. This publication is licensed under CC-BY 4.0, https://creativecommons.org/licenses/by/4.0/. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10215064 |
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