Naohiro Miyamura

Involvement of the calcium-sensing receptor in human taste perception.

By human sensory analyses, we found that various extracellular calcium-sensing receptor (CaSR) agonists enhance sweet, salty, and umami tastes, although they have no taste themselves. These characteristics are known as “kokumi taste” and often appear in traditional Japanese cuisine. Although GSH is a typical kokumi taste substance (taste enhancer), its mode of action is poorly understood. Here, we demonstrate how the kokumi taste is enhanced by the CaSR, a close relative of the class C G-protein-coupled receptors T1R1, T1R2, and T1R3 (sweet and umami receptors). We identified a large number of CaSR agonist γ-glutamyl peptides, including GSH (γ-Glu-Cys-Gly) and γ-Glu-Val-Gly, and showed that these peptides elicit the kokumi taste. Further analyses revealed that some known CaSR agonists such as Ca2+, protamine, polylysine, l-histidine, and cinacalcet (a calcium-mimetic drug) also elicit the kokumi taste and that the CaSR-specific antagonist, NPS-2143, significantly suppresses the kokumi taste. This is the first report indicating a distinct function of the CaSR in human taste perception.

Mechanism of the perception of “kokumi” substances and the sensory characteristics of the “kokumi” peptide, γ-Glu-Val-Gly

Some foods are known to have flavours that cannot be explained by the five basic tastes alone, such as continuity, mouthfulness and thick flavour. It was demonstrated that these sensations are evoked by the addition of kokumi substances, flavour modifiers that have no taste themselves. However, their mode of action has been poorly understood. During a study on the perception of amino acids and peptides, it was found that glutathione (GSH) was one of the agonists of the calcium-sensing receptor (CaSR). We have hypothesized that CaSR is involved in the perception of kokumi substances. We found that all CaSR agonists tested act as kokumi substances and that a positive correlation exists between the CaSR activity of γ-glutamyl peptides and kokumi intensity. Furthermore, the kokumi intensities of GSH and γ-Glu-Val-Gly, a potent kokumi peptide, were significantly reduced by the CaSR-specific antagonist, NPS-2143. These results suggest that CaSR is involved in the perception of kokumi substances. A potent kokumi peptide, γ-Glu-Val-Gly, enhanced sweetness, saltiness and umami when added to 3.3% sucrose, 0.9% NaCl and 0.5% MSG solutions, respectively. In addition, γ-Glu-Val-Gly enhanced the intensity of continuity, mouthfulness and thick flavour when added to chicken soup and reduced-fat cream. These results suggest that γ-Glu-Val-Gly is a potent kokumi peptide and would be useful for improving the flavour of food.

Effect of a kokumi peptide, γ-glutamyl-valyl-glycine, on the sensory characteristics of chicken consommé

BackgroundRecent studies have demonstrated that kokumi substances such as glutathione are perceived through the calcium-sensing receptor (CaSR). Screening by a CaSR assay and sensory evaluation have shown that γ-glutamyl-valyl-glycine (γ-Glu-Val-Gly) is a potent kokumi peptide. In the present study, the sensory characteristics of chicken consommé with added γ-Glu-Val-Gly were investigated using descriptive analysis.ResultsChicken consommé containing γ-Glu-Val-Gly had significantly stronger “umami” and “mouthfulness” (mouth-filling sensation) characteristics than the control sample at a 99% confidence level and significantly stronger “mouth-coating” characteristic than controls at a 95% confidence level.ConclusionsThese data suggest that a kokumi peptide, γ-Glu-Val-Gly, can enhance umami, mouthfulness, and mouth coating, implying that the application of this peptide could contribute to improving the flavor of chicken consommé.

Structure–CaSR–Activity Relation of Kokumi γ-Glutamyl Peptides

Modulation of the calcium sensing receptor (CaSR) is one of the physiological activities of γ-glutamyl peptides such as glutathione (γ-glutamylcysteinylglycine). γ-Glutamyl peptides also possess a flavoring effect, i.e., sensory activity of kokumi substances, which modifies the five basic tastes when added to food. These activities have been shown to be positively correlated, suggesting that kokumi γ-glutamyl peptides are perceived through CaSRs in humans. Our research is based on the hypothesis that the discovery of highly active CaSR agonist peptides will lead to the creation of practical kokumi peptides. Through continuous study of the structure-CaSR-activity relation of a large number of γ-glutamyl peptides, we have determined that the structural requirements for intense CaSR activity of γ-glutamyl peptides are as follows: existence of an N-terminal γ-L-glutamyl residue; existence of a moderately sized, aliphatic, neutral substituent at the second residue in an L-configuration; and existence of a C-terminal carboxylic acid, preferably with the existence of glycine as the third constituent. By the sensory analysis of γ-glutamyl peptides selected by screening using the CaSR activity assay, γ-glutamylvalylglycine was found to be a potent kokumi peptide. Furthermore, norvaline-containing γ-glutamyl peptides, i.e., γ-glutamylnorvalylglycine and γ-glutamylnorvaline, possessed excellent sensory activity of kokumi substances. A novel, practical industrial synthesis of regiospecific γ-glutamyl peptides is also required for their commercialization, which was achieved through the ring opening reaction of N-α-carbobenzoxy-L-glutamic anhydride and amino acids or peptides in the presence of N-hydroxysuccinimide.

Flavour improvement of reduced-fat peanut butter by addition of a kokumi peptide, γ-glutamyl-valyl-glycine

BackgroundRecent studies have demonstrated that kokumi substances, which enhance basic tastes and modify mouthfulness and continuity although they have no taste themselves, are perceived through the calcium-sensing receptor (CaSR). Screening by a CaSR assay and sensory evaluation have shown that γ-glutamyl-valyl-glycine (γ-Glu-Val-Gly) is a potent kokumi peptide. In our previous study, it was reported that the addition of γ-Glu-Val-Gly to chicken consommé significantly enhanced mouthfulness, continuity and thickness. In this study, the effect of γ-Glu-Val-Gly on reduced-fat peanut butter was investigated.ResultsPrior to the evaluation of the effect of γ-Glu-Val-Gly, a comparison test was conducted between full-fat model peanut butter and reduced-fat peanut butter. The sensory attributes in which the score of the full-fat model was significantly higher than that of the reduced-fat sample were used for the evaluation of the effect of γ-Glu-Val-Gly. The addition of γ-Glu-Val-Gly significantly enhanced thick flavour, aftertaste, and oiliness in the reduced-fat peanut butter.ConclusionsA kokumi peptide, γ-Glu-Val-Gly, can enhance thick flavour, aftertaste and oiliness in reduced-fat peanut butter. This suggests that addition of γ-Glu-Val-Gly can improve the flavour of low-fat foods.