Saccharin: Artificial sweetener, bitter tastant, and sweet taste inhibitor

Like all other sweet tasting compounds reported to date, saccharin activates the sweet taste receptor TAS1R2/TAS1R3. Its threshold of activation is in the sub-mM range and the receptor responses saturate at 1-3 mM. In the same concentration range saccharin also activates the human bitter taste receptors TAS2R43 and TAS2R44. They likely mediate saccharin's bitter aftertaste that many subjects complain. At concentrations above 3 mM, saccharin antagonizes activation of TAS1R2/TAS1R3 by itself and other sweeteners. Apparently, saccharin binds to two sites, a high-affinity agonist-binding site and a low-affinity allosteric site. While only the former is occupied at low agonist concentrations leading to receptor activation, the latter becomes occupied at higher agonist concentrations causing receptor inhibition. Thus, we suggest that with rising concentrations the sensory properties of saccharin are impaired by a disproportionate increase in its bitter taste at the expense of its sweet taste.