Year: 2022

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

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

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

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

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

“FUTURE STUDIES should be able to elucidate the precise sites and mechanisms of action, as well as the reason why D2O activates TAS1R2/TAS1R3 in particular, resulting in sweet (but not other) taste. To this end, site-directed mutagenesis as well as determination of the precise structure of the TAS1R2/TAS1R3 receptor will be of key importance.” https://lnkd.in/dzPDm5w View in LinkedIn

TASTING ISOTOPES. “The finding that deuterated water elicits sweet taste via activation of TAS1R/TAS1R2 receptor is of fundamental interest. The difference between hydrogen isotopes is the largest possible isotope effect (doubling of mass in case of deuterium, while tripling in case of tritium), yet deuteration effects on water are generally mild. Nevertheless, water deuteration leads to activation of a GPCR heterodimer to a level that is perceived by humans as sweet taste.” https://lnkd.in/dzPDm5w View in LinkedIn

APPLICATIONS. “While clearly not a practical sweetener, heavy water provides a glimpse into the wide-open chemical space of sweet molecules. Since heavy water may be used in medical procedures, our finding that it can elicit responses of the sweet taste receptor, which is not only located on the tongue but also in other tissues of the human body, represents an important information for clinicians and their patients. Moreover, due to wide application of D2O in chemical structure determination by NMR, chemists will benefit from being aware of the present observations.” https://lnkd.in/dzPDm5w View in LinkedIn

SO ENDS this second and last weekend on a paper showing that heavy water tastes different from normal water. Not only was the finding surprising, but the studies were exceptionally thorough, confirming the result at the taste receptor level. This study is an exemplar of good experimental science, with an initial hypothesis, preliminary findings, testing those findings in alternative systems, and finally nailing the conclusions by these confirmations. View in LinkedIn

E=mc2. “The situation we now face is the following: there are compelling grounds to deny the inter-convertibility and equivalence of mass and energy, and yet such a denial seems hard to reconcile with important experimental phenomena. What should we make of this?” An outstanding essay by Kevin Coffey, a philosopher. https://lnkd.in/dKhwtbs View in LinkedIn