Bitter Odorants and Odorous Bitters: Toxicity and Human TAS2R Targets

[Image: see text] Flavor is perceived through the olfactory, taste, and trigeminal systems, mediated by designated GPCRs and channels. Signal integration occurs mainly in the brain, but some cross-reactivities occur at the receptor level. Here, we predict potential bitterness and taste receptors targets for thousands of odorants. BitterPredict and BitterIntense classifiers suggest that 3–9% of flavor and food odorants have bitter taste, but almost none are intensely bitter. About 14% of bitter molecules are expected to have an odor. Bitterness is more common for unpleasant smells such as fishy, amine, and ammoniacal, while non-bitter odorants often have pleasant smells. Experimental toxicity values suggest that fishy ammoniac smells are more toxic than pleasant smells, regardless of bitterness. TAS2R14 is predicted as the main bitter receptor for odorants, confirmed by in vitro profiling of 10 odorants. The activity of bitter odorants may have implications for physiology due to ectopic expression of taste and smell receptors.