Endocrine Abstracts

Taste is an overriding determinant of food choice and leads to the development of preferences impacting on nutrition and eventually health. To investigate the molecular basis of gustation and its link to nutritional behaviour, we isolated all 25 members of the human bitter taste receptor gene family, TAS2Rs, and established their expression profile on the tongue. Using functional assays we identified the cognate bitter compounds for ∼half of the encoded receptors. Our data suggest that TAS2Rs appear to be broadly tuned to detect compounds with common structural motifs, explaining how humans are capable of perceiving thousands of bitter substances with a small set of receptors. This broad tuning is likely caused by the presence of multiple binding sites for various bitter compounds on the TAS2Rs. Our experiments also revealed that the biochemical properties of the receptors define perceptual sensitivity of individuals. Moreover, frequently occurring polymorphisms in TAS2R genes determine numerous receptor variants, which can differ in the sensitivities for their cognate bitter compounds up to 1000 fold, thereby generating perceptual variability in the population. How far receptor mechanisms determine tasting is shown for saccharin, a compound that taste sweet through activation of the sweet taste receptor at low and moderate concentration, with an off-taste caused by its ability to activate two TAS2R bitter taste receptors simultaneously and to block the sweet taste receptor at higher concentrations.

To date direct evidence is still missing that convincingly proves or disproves the impact of gustation on intake behaviour. However, strong circumstantial evidence comes from the phylogenetic analysis of human TAS2R genes and from the analysis of TAS2R polymorphisms and taster phenotypes that evolved independently in chimanzees and humans as well as from an association study identifying a TAS2R16 allele as a risk factor of alcohol dependence. Taken together, our data strongly suggest that genetics and peripheral taste receptor mechanisms govern gustatory perception and perceptual variability in the population with a probable impact on nutrition and health.