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MOLECULAR DOSE RESPONSE. “Next, TAS1R2/TAS1R3 receptor along with the chimeric Gα16gust44 subunit were transiently expressed, and the functionality was illustrated by dose-dependent response to D-glucose (Fig. 6c). Finally, and in agreement with calcium imaging, we found that 10% D2O activated these cells. Activation by 100% D2O was even more pronounced (Fig. 6d).” https://lnkd.in/dzPDm5w View in LinkedIn

NUCLEAR QUANTUM EFFECT. “At a molecular level, this general behavior may be traced back to the slightly stronger hydrogen bonding in D2O vs H2O, which is due to a nuclear quantum effect, namely difference in zero-point energy. Biologically relevant situations where one may expect strong nuclear quantum effects as implications of H/D substitution directly involve proton or deuteron transfer. Unless a yet unknown indirect mechanism is involved, this is not the case for the TAS1R2/TAS1R3 sweet taste receptor, thus the nuclear quantum effect is probably weak in the present case.” https://lnkd.in/dzPDm5w View in LinkedIn

CELLULAR DOSE RESPONSE. “We further used an IP1 assay on non-transfected HEK 293T cells, where we observed that dose-dependent curves of carbachol—an agonist of the endogenous muscarinic receptor 3 (M3)47—did not show any difference between H2O and D2O-based media (Fig. 6a) and that cell medium that had either 10% or 100% D2O, did not activate basal IP1 accumulation (Fig. 6b).” https://lnkd.in/dzPDm5w View in LinkedIn

MOLECULAR MECHANISM. “Our findings point to the human sweet taste receptor TAS1R2/TAS1R3 as being essential for sweetness of D2O. Molecular dynamics simulations show, in agreement with experiment, that proteins in general are slightly more rigid and compact in D2O than in H2O.” https://lnkd.in/dzPDm5w View in LinkedIn

TITRATION. “The inhibitory effect of lactisole on D2O-activation of the human sweet taste receptor was confirmed using an IP1 assay, while lactisole exposure had no effect on cells treated with pure H2O water, as expected (Fig. 5c). As a control, 960 mM D-glucose elicited increase in IP1 levels in TAS1R2/TAS1R3 expressing cell, which was inhibited in the presence of lactisole.” https://lnkd.in/dzPDm5w View in LinkedIn

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