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DATA SUMMARY. “In support of these observations we have demonstrated that HEK 293T cells transfected with TAS1R2/TAS1R3 and Gα16gust chimera, but not the non-transfected cells, are activated by D2O, as measured by IP1 accumulation compared to control values. Finally, taste experiments on mice show that these animals do not prefer D2O over H2O.” https://lnkd.in/dzPDm5w View in LinkedIn

AFFIRMATION. “As seen in Fig. 5a, D2O at 1.85 M and 5.84 M concentrations in H2O (3.3% and 10.4%, respectively) elicited robust responses in TAS1R2/TAS1R3 expressing cells. The strong reduction or absence of D2O-elicited fluorescence response in the presence of lactisole confirmed the dependence on TAS1R2/TAS1R3.” https://lnkd.in/dzPDm5w View in LinkedIn

SWEET SUPPRESSION. “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 domain30, 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.” https://lnkd.in/dzPDm5w View in LinkedIn

COMBINATIONS. “Furthermore, D2O added to perceived sweetness of low concentrations of other sweeteners. In contrast, it did not elicit umami or bitter taste on its own, nor did it add to the umami taste perception of MSG. D2O did not add to the bitterness of quinine, and reduced the perceived bitterness of 0.1 mM quinine, in agreement with the known effect of bitterness suppression by sweet molecules.” https://lnkd.in/dzPDm5w View in LinkedIn

SURPRISE FINDING. “Being only isotopically different from H2O, in principle, D2O should be indistinguishable from H2O with regard to taste, namely it should have no taste of its own. Yet, we illustrate that human subjects consistently perceive D2O as being slightly sweet and significantly sweeter than H2O.” https://lnkd.in/dzPDm5w View in LinkedIn

PRIMARY EFFECT. “Here, we have studied the taste of D2O and H2O per se, not related to washing away of sweet taste inhibitors. Using psychophysics protocols, we show that humans differentiate between D2O and H2O based on taste alone. Importantly, by employing gas chromatography/mass spectrometry analysis we demonstrate that the sweet taste of deuterated water is not due to impurities.” https://lnkd.in/dzPDm5w View in LinkedIn

SWEET TASTE INHIBITORS. “Sweet taste never ceases to surprise. Over a decade ago, 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.” https://lnkd.in/dzPDm5w View in LinkedIn

AQUEOUS MILIEU. “Structural fluctuations of most residues (particularly those directly exposed to the aqueous environment) and of the protein as a whole are slightly attenuated in D2O, in which environment the protein is also somewhat more compact than in H2O (Fig. 7b). Additional simulations on other representative systems show that the rigidifying effect of heavy water is apparent also in small soluble proteins.” https://lnkd.in/dzPDm5w View in LinkedIn

BINDING CONFIGURATION. “Figure 7b shows the time evolution of the radius of gyration of the TMD domain, while Fig. 7c and d presents the root mean square fluctuations (RMSF) of individual residues of the proteins superimposed on its structure and plotted in a graph together with the mean value of RMSF. A small but significant difference is apparent in the behavior of the protein in H2O vs D2O.” https://lnkd.in/dzPDm5w View in LinkedIn

RECEPTOR BINDING. “H2O and D2O have mutually slightly shifted densities inside the protein cavity, with H2O overlapping better than D2O with the modeled water positions. Furthermore, MD simulations show clustered water molecules close to the lactisole binding site. These internal positions may have a differential effect between H2O and D2O, though differences between the averaged water densities are not very pronounced.” https://lnkd.in/dzPDm5w View in LinkedIn