Bitter Odorants and Odorous Bitters: Toxicity and Human TAS2R Targets

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.