TAS2R39
receptor / receptor-tas2r39
TAS2R39 is a human bitter taste receptor subtype activated by galloylated tea catechins and many (iso)flavonoids.
On this page (6 sections)
Reading the bitterness
TAS2R39 is a human bitter taste receptor subtype activated by galloylated tea catechins and many (iso)flavonoids. In cell-based assays using hTAS2R39-expressing cultured cells, both epicatechin gallate (ECg) and epigallocatechin gallate (EGCg) showed clear responses at 300 micromolar, with ECg eliciting the strongest response among the tested catechins, followed by EGCg. By contrast, the responses to non-galloylated epicatechin (EC) and epigallocatechin (EGC) were far weaker.
A separate study using a large set of structurally similar (iso)flavonoids (68 to 70 compounds) found that 70 of them activated hTAS2R39, with activation thresholds ranging from 0.12 to 500 micromolar, demonstrating that this receptor exhibits broad tuning. When the same research group independently retested 4 tea catechins, thresholds were quantified as 32 micromolar for ECG and EGCG, 250 micromolar for EC, and 500 micromolar for EGC. The ordering—galloylated catechins (ECG, EGCG) having lower thresholds than non-galloylated catechins (EC, EGC), that is, activating more strongly—aligns with findings from prior studies. However, compared to the thresholds reported in earlier work (all 4 compounds in the 10 to 30 micromolar range), this independent retest reports thresholds approximately 10-fold higher for non-galloylated catechins, indicating that absolute values differ between assays.
A separate independent cell assay confirmed that (−)-epicatechin activates 3 receptors—TAS2R4, TAS2R5, and TAS2R39—providing corroboration from a different research group's experimental system for the finding that catechin-scaffold compounds are agonists of TAS2R39.
A review states that among dipeptides, Trp-Trp and Leu-Trp activate TAS2R39, while other Trp-containing combinations such as Trp-Leu do not. Among tripeptides, both Trp-Trp-Trp and Leu-Leu-Leu activate TAS2R39, the review also notes. The review further describes that larger peptides arising during cheese maturation also activate TAS2R39.
The same review notes that soybeans contain TAS2R39 agonists among their isoflavone compounds, stating that genistein (the aglycone) activates both TAS2R39 and TAS2R14, while on the glycoside side there are compounds that act specifically on TAS2R39. This describes the breadth of TAS2R39 substrates, extending from peptides to soy isoflavone glycosides.
Sources for this overview
Checked for this overview: Used to support the response-strength order of galloylated catechins at 300 micromolar
Checked for this overview: Used to support background description of broad tuning activating 70 compounds / Used to support quantified threshold values for 4 catechins from the independent retest / Used to support cross-literature comparison showing approximately 10-fold difference
Different phenolic compounds activate distinct human bitter taste receptors
Checked for this overview: Used to support independent confirmation of epicatechin activation from a different laboratory
The Hidden One: What We Know About Bitter Taste Receptor 39
Checked for this overview: Activation of Trp-Trp and other di- and tripeptides, and cheese-maturation peptides / Identification of 4 soy isoflavone glycoside-specific agonists
Follow the connections
tea catechins →activates→ TAS2R39
bitter peptides →activates→ TAS2R39
soy isoflavone glycosides →activates→ TAS2R39
Structured claims — open a section to read each claim's confidence, evidence and limits
Mechanism and receptors (3)
Scope: A cultured-cell assay. A clear response to 300 uM ECg and EGCg. ECg is strongest, followed by EGCg, with EC and EGC far weaker
Note: The abstract reports only a single concentration (300 uM). The receptor is broadly tuned (many flavonoids also activate TAS2R39).
Show data
compound-catechins —activate→ receptor-tas2r39Scope: Layer: cell (description in primary research summarized by the review).
Note: A review (Jalševac et al. 2022) summarizes primary research on amino acids and peptides (references 40-42); this is a second-hand citation. Primary sources have not been read. The relevant section of the review describes only the activation of these receptors by the peptides and does not characterize the peptides themselves as 「苦い」 (in translation: "bitter").
Show data
compound-class-bitter-peptides —activates→ receptor-tas2r39Scope: Layer: cell (description in primary research summarized by the review).
Note: A review (Jalševac et al. 2022) summarizes primary research on soy isoflavones (reference 25); this is a second-hand citation. Primary source has not been read.
Show data
compound-class-soy-isoflavone-glycosides —activates→ receptor-tas2r39