Activation of the calcium-sensing receptor by glutathione maillard products: Implications for kokumi sensation

Kokumi peptides, such as glutathione (GSH), activate the calcium-sensing receptor (CaSR) in taste buds, evoking distinct sensory attributes. Foods containing GSH-derived Maillard reaction products (MRPs) often exhibit kokumi characteristics, but their direct interaction with CaSR remains unclear. In this study, GSH was thermally reacted with reducing sugars (glucose, xylose) at 80 °C, 120 °C, and 150 °C. The resulting MRPs were evaluated for browning, volatile profiles (GC–MS), and CaSR activation using a fluorescence-based cell assay. GSH–xylose MRPs showed greater browning and distinct volatile profiles compared to GSH–glucose MRPs. Notably, GSH–glucose MRPs showed highest CaSR activity at >120 °C, followed by GSH–xylose MRPs, likely acting as positive allosteric modulators. This provides the first evidence of allosteric modulation of CaSR by GSH–sugar MRPs, offering mechanistic insight into receptor interaction. However, the lack of sensory validation remains a limitation, and further studies are needed to confirm the perceptual relevance of these findings.