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Abstract
Hydrogen to deuterium isotopic substitution has only a minor effect on physical and chemical properties of water and, as such, is not supposed to influence its neutral taste. Here we conclusively demonstrate that humans are, nevertheless, able to distinguish D2O from H2O by taste. Indeed, highly purified heavy water has a distinctly sweeter taste than same-purity normal water and can add to perceived sweetness of sweeteners. In contrast, mice do not prefer D2O over H2O, indicating that they are not likely to perceive heavy water as sweet. HEK 293T cells transfected with the TAS1R2/TAS1R3 heterodimer and chimeric G-proteins are activated by D2O but not by H2O. Lactisole, which is a known sweetness inhibitor acting via the TAS1R3 monomer of the TAS1R2/TAS1R3, suppresses the sweetness of D2O in human sensory tests, as well as the calcium release elicited by D2O in sweet taste receptor-expressing cells. The present multifaceted experimental study, complemented by homology modelling and molecular dynamics simulations, resolves a long-standing controversy about the taste of heavy water, shows that its sweet taste is mediated by the human TAS1R2/TAS1R3 taste receptor, and opens way to future studies of the detailed mechanism of action.
Ben Abu, Mason and colleagues use molecular dynamics, cell-based experiments, mouse models, and human subjects to determine that, unlike ordinary water, heavy water tastes sweet to humans, but not mice. Mechanistically, this effect is mediated by the human TAS1R/TAS1R3 sweet taste receptor.
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1 The Hebrew University of Jerusalem, The Institute of Biochemistry, Food Science and Nutrition, The Robert H Smith Faculty of Agriculture, Food and Environment, Rehovot, Israel (GRID:grid.9619.7) (ISNI:0000 0004 1937 0538); The Hebrew University of Jerusalem, The Fritz Habe Center for Molecular Dynamics, Jerusalem, Israel (GRID:grid.9619.7) (ISNI:0000 0004 1937 0538)
2 Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry, Prague 6, Czech Republic (GRID:grid.418095.1) (ISNI:0000 0001 1015 3316)
3 Leibniz-Institute for Food Systems Biology at the Technical University of Munich, Freising, Germany (GRID:grid.506467.6)