Bitter peptides activate hTAS2Rs, the human bitter receptors

Abstract

Fermented food contains numerous peptides derived from material proteins. Bitter peptides formed during the fermentation process are responsible for the bitter taste of fermented food. We investigated whether human bitter receptors (hTAS2Rs) recognize bitterness of peptides with a heterologous expression system. HEK293 cells expressing hTAS2R1, hTAS2R4, hTAS2R14, and hTAS2R16 responded to bitter casein digests. Among those cells, the hTAS2R1-expressing cell was most strongly activated by the synthesized bitter peptides Gly-Phe and Gly-Leu, and none of the cells was activated by the non-bitter dipeptide Gly-Gly. The results showed that these bitter peptides, as well as many other bitter compounds, activate hTAS2Rs, suggesting that humans utilize these hTAS2Rs to recognize and perceive the structure and bitterness of peptides.

Activation of the hTAS2R14 Human Bitter-Taste Receptor by (−)-Epigallocatechin Gallate and (−)-Epicatechin Gallate

“…Some studies have reported hTAS2R14 to be a broadly tuned receptor. 16,[18][19][20][21] Although the homology between hTAS2R14 and 39 at the amino acid level is only 29%, hTAS2R14 and 39 have such common agonists as quinine, chlorpheniramine, azathioprine, diphenidol, and genistein. 16,20) Furthermore, we revealed in this study that ECg and EGCg were also common agonists to hTAS2R14 and 39.…”

Genetics of Taste and Smell

“…29 So the ability to sense bitterness may serve other purposes in addition to poison detection. For instance, when proteins are fermented, some of the protein products are bitter, 30 so the bitter taste system may also detect decayed proteins.…”

“…39 Other bitter molecules stimulate multiple receptors, and the loss of one may decrease but not eliminate the ability to detect that particular bitter molecule. 30,39,47,65-73 The perception of PTC is probably an extreme case of individual variation in bitter perception.…”

Bitter peptides and bitter taste receptors

“…hT2R46 is a broadly tuned bitter receptor for sesquiterpene lactones, strychnine, and so on [110]. And hT2R1 is tentatively a receptor for bitter peptides [111]. Because of the large family of bitter receptor genes that evolved to recognize bitter sensation from of a wide range of chemicals, identification of ligands for each bitter receptor is necessary to establish the entire bitter tasting profile for humans.…”

“…These 25 hT2Rs may, in a complementary manner, recognize a specific chemical structure for each receptor to perceive numerous bitter substances. For example, casein hydrolysate, which contains numerous bitter peptides with different structures, can activate several T2Rs [111]. Moreover, two bitter peptides, Gly-Phe and Gly-Leu, also activate all hT2R-expressing cells tested, whereas a nonbitter peptide, Gly-Gly, does not.…”