Bitter Odorants and Odorous Bitters: Toxicity and Human TAS2R Targets

Flavor is perceived through the olfactory, taste, andtrigeminalsystems, mediated by designated GPCRs and channels. Signal integrationoccurs mainly in the brain, but some cross-reactivities occur at thereceptor level. Here, we predict potential bitterness and taste receptorstargets for thousands of odorants. BitterPredict and BitterIntenseclassifiers suggest that 3-9% of flavor and food odorants havebitter taste, but almost none are intensely bitter. About 14% of bittermolecules are expected to have an odor. Bitterness is more commonfor unpleasant smells such as fishy, amine, and ammoniacal, whilenon-bitter odorants often have pleasant smells. Experimental toxicityvalues suggest that fishy ammoniac smells are more toxic than pleasantsmells, regardless of bitterness. TAS2R14 is predicted as the mainbitter receptor for odorants, confirmed by in vitro profiling of 10 odorants. The activity of bitter odorants may haveimplications for physiology due to ectopic expression of taste andsmell receptors.

Automated summary

Flavor is perceived through multiple systems and receptors, with some cross-reactivity between taste and odor receptors. This study predicts the bitterness and taste receptor targets of thousands of odorants, finding that a small percentage have a bitter taste and even fewer are intensely bitter. Bitter odorants are more commonly associated with unpleasant smells, while non-bitter odorants often have pleasant smells. The main bitter receptor for odorants is predicted to be TAS2R14, and its activity may have physiological implications through the expression of taste and smell receptors.