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.
Highlights
Water was shown to elicit sweet taste by rinsing away inhibitors of sweet taste receptors, both in human sensory experiments and in cell-based studies. This effect was explained in terms of a two-state model, where the receptor shifts to its activated state when released from inhibition by rinsing with water[43]
We have studied the taste of D2O and H2O per se, not related to washing away of sweet taste inhibitors
We show that humans differentiate between D2O and H2O based on taste alone
Summary
Water was shown to elicit sweet taste by rinsing away inhibitors of sweet taste receptors, both in human sensory experiments and in cell-based studies. A further important finding is that lactisole, which is an established blocker of the TAS1R2/TAS1R3 sweet taste receptor that acts at the TAS1R3 transmembrane domain[30], suppresses both the sweet perception of D2O in sensory tests, as well as the activation of TAS1R/TAS1R3 in calcium imaging and in IP1 cell-based assays. Our findings point to the human sweet taste receptor TAS1R2/
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