Umami Receptor Research Articles

Umami polypeptide detection system targeting the human T1R1 receptor and its taste-presenting mechanism

Umami is one of five basic tastes, the elucidation of its mechanism by the study of the interaction between umami polypeptides and hT1R1 umami receptors is of great significance. However, research on umami peptides targeting human T1R1 receptors is lacking, and the molecular mechanism remains elusive. Here, we successfully established a system to detect umami peptides targeting human T1R1 receptors by fluorescence spectroscopy, Surface Plasmon Resonance (SPR) and computational simulation. The sensory evaluation, calculated Kd value, and experimental affinity results between the four selected umami peptides (GRVSNCAA, KGDEESLA, KGGGGP, and TGDPEK) and glutamate were tested using this system, and all matched well. The maximum Ka value of GRVSNCAA was 479.55 M-1, and the minimum affinity of TGDPEK was 2.67 M-1. Computational simulations showed that the different peptide binding sites in the hT1R1 binding pocket occupied due to conformational changes are important factors for different taste thresholds, and that peptide hydrophobicity plays an important role in regulating affinity. Thus, our study enables rapid screening of high-intensity umami peptides and the development of T1R1 receptor-based umami detection sensors.

Preparation, Sensory Characterization, and Umami-Enhancing Mechanism of Novel Peptide Glycoconjugates

Previous studies supposed that Amadori rearrangement products (ARPs) of peptides might have better umami-enhancing abilities. To confirm this, five ARPs (EP-ARP, AH-ARP, EE-ARP, β-AH-ARP, RFPHADF-ARP) were synthesized using a food-grade preparation method, and their chemical structures were clearly demonstrated by mass spectrometry and 1D/2D NMR. Sensory experiments showed that ARPs had better umami-enhancing abilities than the corresponding peptides in this research, though their enhancing performance varied. ARPs showed a synergistic effect with multiple umami substances (MSG and GMP), while their corresponding peptides did not. RFPHADF-ARP had good umami-enhancing capacity, despite that RFPHADF was a bitter peptide without any umami/umami-enhancing property. RFPHADF-ARP could bind to the T1R3, which is beneficial to the stability of the active conformation of the umami receptor. The introduction of glucose via the Maillard reaction increased the binding force of RFPHADF with the umami receptor by influencing the electron density distribution and offering more binding groups (hydroxide group).

Impact of sweet, umami, and bitter taste receptor (TAS1R and TAS2R) genomic and expression alterations in solid tumors on survival

Originally identified on the tongue for their chemosensory role, the receptors for sweet, umami, and bitter taste are expressed in some cancers where they regulate important cellular processes including apoptosis and proliferation. We examined DNA mutations (n = 5103), structural variation (n = 7545), and expression (n = 6224) of genes encoding sweet or umami receptors (TAS1Rs) and bitter receptors (TAS2Rs) in 45 solid tumors subtypes compared to corresponding normal tissue using The Cancer Genome Atlas and the Genotype Tissue Expression Project databases. Expression of TAS1R and TAS2R genes differed between normal and cancer tissue, and nonsilent mutations occurred in many solid tumor taste receptor genes (~ 1–7%). Expression levels of certain TAS1Rs/TAS2Rs were associated with survival differences in 12 solid tumor subtypes. Increased TAS1R1 expression was associated with improved survival in lung adenocarcinoma (mean survival difference + 1185 days, p = 0.0191). Increased TAS2R14 expression was associated with worse survival in adrenocortical carcinoma (−1757 days, p < 0.001) and esophageal adenocarcinoma (−640 days, p = 0.0041), but improved survival in non-papillary bladder cancer (+ 343 days, p = 0.0436). Certain taste receptor genes may be associated with important oncologic pathways and could serve as biomarkers for disease outcomes.

Taste mechanism of umami peptides from Chinese traditional fermented fish (Chouguiyu) based on molecular docking using umami receptor T1R1/T1R3

Umami peptides formed during fermentation of Chouguiyu contribute to its unique taste. In this study, the umami taste of peptide extract from Chouguiyu was improved after fermentation, as determined by sensory evaluation. After umami peptide identification using peptidomics, molecular docking with T1R1/T1R3 was used to evaluate the likely taste mechanism. There were 400 umami peptides identified in Chouguiyu, most of which were significantly enhanced after fermentation. These peptides were hydrolyzed from 77 precursor proteins, mainly including myosin, troponin, and titin, at multiple locations. The umami structures in the six core umami peptides with the lowest binding energy were easy to connect with Ser, Glu, His, Gln, Arg and Lys residues in T1R3 through hydrogen bond and salt bridge. The hydrogen bond, hydrophilcity, aromatic interaction, and solvent accessible surface were the main interaction surface forces. This study provides important information of the unique taste formation in Chouguiyu based on umami peptides.

Extra-Oral Taste Receptors-Function, Disease, and Perspectives.

Taste perception is crucial for the critical evaluation of food constituents in human and other vertebrates. The five basic taste qualities salty, sour, sweet, umami (in humans mainly the taste of L-glutamic acid) and bitter provide important information on the energy content, the concentration of electrolytes and the presence of potentially harmful components in food items. Detection of the various taste stimuli is facilitated by specialized receptor proteins that are expressed in taste buds distributed on the tongue and the oral cavity. Whereas, salty and sour receptors represent ion channels, the receptors for sweet, umami and bitter belong to the G protein-coupled receptor superfamily. In particular, the G protein-coupled taste receptors have been located in a growing number of tissues outside the oral cavity, where they mediate important processes. This article will provide a brief introduction into the human taste perception, the corresponding receptive molecules and their signal transduction. Then, we will focus on taste receptors in the gastrointestinal tract, which participate in a variety of processes including the regulation of metabolic functions, hunger/satiety regulation as well as in digestion and pathogen defense reactions. These important non-gustatory functions suggest that complex selective forces have contributed to shape taste receptors during evolution.

Remodeling of the ryanodine receptor isoform 1 channel regulates the sweet and umami taste perception of Rattus norvegicus

Sweet and umami tastes are elicited by sweet and umami receptors on the tongue and palate epithelium, respectively. However, the molecular machinery allowing the taste reaction remains incompletely understood. Through a phosphoproteomic approach, we identified the key proteins that trigger taste mechanisms based on phosphorylation cascades. Ryanodine receptor isoform 1 (RYR1) was further verified by sensory and behavioral assays. We propose a model of RYR1-mediated sweet/umami signaling in which the RYR1 channel, which mediates Ca2+ release from the endoplasmic reticulum, is closed by dephosphorylation in bud tissue after sweet/umami treatment. The alteration in Ca2+ content in the cytosol induces transient membrane depolarization and generates a cell current for taste signal transduction. We demonstrate that RYR1 is a new channel involved in the regulation of sweet/umami signal transduction and propose a “metabolic clock” notion based on sweet/umami sensing. Our study provides a valuable foundation for a system-level understanding of the taste perception mechanism.

Research progress in the screening and evaluation of umami peptides.

Umami is an important element affecting food taste, and the development of umami peptides is a topic of interest in food-flavoring research. The existing technology used for traditional screening of umami peptides is time-consuming and labor-intensive, making it difficult to meet the requirements of high-throughput screening, which limits the rapid development of umami peptides. The difficulty in performing a standard measurement of umami intensity is another problem that restricts the development of umami peptides. The existing methods are not sensitive and specific, making it difficult to achieve a standard evaluation of umami taste. This review summarizes the umami receptors and umami peptides, focusing on the problems restricting the development of umami peptides, high-throughput screening, and establishment of evaluation standards. The rapid screening of umami peptides was realized based on molecular docking technology and a machine learning method, and the standard evaluation of umami could be realized with a bionic taste sensor. The progress of rapid screening and evaluation methods significantly promotes the study of umami peptides and increases its application in the seasoning industry.

Biomimetic ion nanochannels for sensing umami substances

Umami is one of the basic taste sensing, and represents the recognition of N-containing compounds capable of evaluating the nutritious contents of food. Although several sensors have been developed, the assessment of umami intensity remains challenging due to the limitations of sensor specificity, sensitivity, and performance stability. Here we present a biomimetic conical nanochannels system integrated with Venus flytrap (VFT) domain from human umami receptor T1R1 subunit to meet the concern. By taking advantage of sensitive transmembrane ionic flux change, the functional nanochannels could precisely distinguish umami substances from other tastants. Detailed mechanism analysis reveals that specific binding between T1R1 and umami substances triggers local conformation change and surface charge redistribution of the protein, which modulates the ionic current. This study initiates the application of nanochannel device in taste perception, which could help to disclose umami perception mechanism and screen new umami substances.

Sweet and umami receptors are expressed in the heart and regulate contractility

The tongue can distinguish between five different tastes via the taste receptors, which are G-protein coupled receptors (GPCRs). There are two classes of taste receptors, the TAS1 (T1) and TAS2 (T2) families, and the T1R1-T1R3 dimer senses the umami taste and T1R2-T1R3 senses the sweet taste. Recently, the taste receptors have also been found in the brain, lungs, intestine and pancreas, where they sense changes in the nutrient environment and respond through GPCR signalling. Given the importance of glucose and amino acid metabolism in the heart, we hypothesized that the sweet and umami taste receptors have an important function in the heart.

Identification and comparison of umami-peptides in commercially available dry-cured Spanish mackerels (Scomberomorus niphonius)

Dry-cured Spanish mackerel (DSM; Scomberomorus niphonius) is a popularity worldwide dry-cured marine fish product due to its salty and umami flavor. Umami peptides from eight commercial DSMs were identified and compared, and their molecular mechanisms were evaluated via molecular simulation. The results showed that the sequence of peptides varied in different DSMs, wherein only ten sequences were repeated across multiple samples and the remaining 19 were detected in only one sample. The sensory characteristics of eight repeated peptides were evaluated, and four were found to exhibit umami taste and umami-enhancing effects, including Arg-Asp, Asp-Gly-Val, Asp-Arg, and Asp-Lys. They all had a strong affinity for umami receptors, and several amino acid residues of the receptors were mobilized as binding sites to form hydrogen bonds and hydrophobic bonds in ligand-receptor interactions. These results indicated that DSM was rich in umami and umami-enhancing peptides, but their sequence were different in different DSMs.

Isolation and screening of umami peptides from preserved egg yolk by nano-HPLC-MS/MS and molecular docking

The material basis leading to the rich umami flavor of preserved egg yolk is poorly understood. This study used nano-high-performance liquid chromatography − tandem mass spectrometry (nano-HPLC-MS/MS) to isolate, identify, and screen umami peptides from preserved egg yolk. Five novel umami peptides—AGFMPLP, APYSGY, PPMF, SLSSLMK, and VAMNPVDHPH—were identified. Molecular docking showed that Phe527 on the taste receptor T1R1/T1R3 (T1R1, taste receptor type 1 member 1; T1R3, taste receptor type 1 member 3) was the key interaction site. Hydrogen bonding, electrostatic interactions, and hydrophobic interactions were the main binding forces between T1R1/T1R3 and umami peptides. These results contribute to understanding the umami peptides in preserved egg yolk and the interaction mechanism between umami peptides and umami receptors.

Role of feeding specialization in taste receptor loss: insights from sweet and umami receptor evolution in Carnivora.

Controversy and misunderstanding surround the role of feeding specialization in taste receptor loss in vertebrates. We refined and tested the hypothesis that this loss is caused by feeding specializations. Specifically, feeding specializations were proposed to trigger time-dependent process of taste receptor loss through deprivation of benefit of using the receptor's gustatory function. We propose that this process may be accelerated by abiotic environmental conditions or decelerated/stopped because of extragustatory functions of the receptor's protein(s). As test case we used evolution of the sweet (TAS1R2+TAS1R3) and umami (TAS1R1+TAS1R3) receptors in Carnivora (dogs, cats, and kin). We predicted these receptors' absence/presence using data on presence/absence of inactivating mutations in these receptors' genes and data from behavioral sweet/umami preference tests. We identified 20 evolutionary events of sweet (11) or umami (9) receptor loss. These events affected species with feeding specializations predicted to favor sweet/umami receptor loss (27 and 22 species, respectively). All species with feeding habits predicted to favor sweet/umami receptor retention (11 and 24, respectively) were found to retain that receptor. Six species retained the sweet (5) or umami (1) receptor despite feeding specialization predicted to favor loss of that receptor, which can be explained by the time dependence of sweet/umami receptor loss process and the possible decelerating effect of TAS1R extragustatory functions so that the sweet/umami receptor process is ongoing in these species. Our findings support the idea that feeding specialization leads to taste receptor loss and is the main if not only triggering factor for evolutionary loss of taste receptors.

Identification of novel umami molecules via QSAR models and molecular docking.

Umami substances can increase the overall taste of food and bring pleasure to people. However, it is still challenging to identify the umami molecules through virtual screening due to the crystal structure of the umami receptor being undefined. Herein, based on the hypothesis that the molecules with bitter and sweet taste characteristics may be umami molecules, this study proposed an in silico method to identify novel umami-tasting molecules in batch from SWEET-DB and BitterDB databases via the QSAR models, PCA, molecular docking and electronic tongue analysis. In total, 169 potential umami molecules were identified through QSAR modeling, PCA, and molecular docking. Of the 169 molecules, 18 were randomly selected, and all were identified as umami molecules via electronic tongue analysis. Among the 18 chosen molecules, 10 molecules could be traced back to their concentration range in food, and finally, 8 molecules were predicted to be nontoxic. This work provides a simple and efficient strategy to identify novel umami molecules, holding an excellent promise for demonstrating the crystal structure of umami receptors and taste-sensing mechanisms. Furthermore, this study opens the possibility for the practical application of new umami molecules in food.

Study on the distribution of umami receptors on the tongue and its signal coding logic based on taste bud biosensor

Taste signals are uniformly encoded and transmitted to the brain's taste center by taste buds, and the process has not been systematically studied for several decades. The aim of this work was to investigate the distribution of umami receptors on the tongue and its signal coding logic based on the taste bud biosensors. Taste bud biosensors were constructed by immobilizing the taste bud tissues from different tongue regions of the rabbit to the glassy carbon electrode surface; The Shennong information equations were used to analysis the pattern of umami receptors to encode ligands information; The signal amplification capabilities of two types umami receptors (T1R1/T1R3 and mGluRs) were analyzed for the two ligands (L-monosodium glutamate (MSG) and disodium 5′-inosinate (IMP)). The results showed that each taste bud biosensor could sense MSG and IMP with different response currents based on enzyme-substrate kinetics. There was only a small fraction of a great quantity of metabotropic glutamate receptors (mGluRs) could be activated to encode MSG signal. Importantly, T1R1 was more expressed in the rostral tongue cells whose sensitivity to MSG was nearly 100 times stronger than that of caudal tongue cells. The method we proposed made it possible to reveal the distribution and signals coding logic of umami receptors for ligands, which showed great potential to explain the interaction mechanism of umami substances with their receptors more accurately and to develop of artificial intelligent taste sensory.

Human-like performance umami electrochemical biosensor by utilizing co-electrodeposition of ligand binding domain T1R1-VFT and Prussian blue

Over the past decades, due to the desire for artificial umami flavors, apparatuses for detecting the umami taste have constantly been developed. Nevertheless, most information on umami is still acquired through human sensory assessment, which makes it difficult to establish an umami standard or quantify the umami flavor. In this study, the ligand binding domain called venus flytrap (VFT) domain of the umami taste receptor protein T1R1 was used as a recognition element, and an electrochemical biosensor based on a double-signal amplification strategy was constructed using single-walled carbon nanotubes (SWCNTs) and Prussian blue (PB). Moreover, the umami taste of four representative umami substances, inosine-5′-monophosphate (IMP), monosodium L-glutamate (MSG), beefy meaty peptide (BMP), and sodium succinate (WSA), were successfully quantitatively measured using differential pulse voltammetry (DPV) at an electrochemical workstation. Based on an equation (S/N = 3), the low detection limits (LODs) of IMP, MSG, BMP, and WSA were 0.1, 0.1, 0.1, and 0.01 pM, respectively. Meanwhile, a normalized signal intensity of more than 90% was kept for 4 days. The results showed that the biosensor could be used to detect umami substances with high sensitivity and selectivity, and was shown to have human-like performance. To develop the T1R1-VFT biosensor using the above-mentioned method, we utilized the ligand binding domain of the human umami receptor, rather than the entire umami receptor protein, which had a complex structure, having the following advantages: volume reduction, simplicity, and stability. This method has great potential for the detection of umami tastes, instead of using sensory evaluation, and for the development of new artificial flavorings.

Abstract P514: The Role Of Sweet And Umami Taste Receptors In The Heart

The tongue can distinguish between five different tastes via the taste receptors, which are G-protein coupled receptors (GPCRs). There are two classes of taste receptors, the TAS1 (T1) and TAS2 (T2) families, and the T1R1-T1R3 dimer senses the umami taste and T1R2-T1R3 senses the sweet taste. Recently, the taste receptors have also been found in the brain, lungs, intestine and pancreas, where they sense changes in the nutrient environment and respond through GPCR signalling. Given the importance of glucose and amino acid metabolism in the heart, we hypothesized that the sweet and umami taste receptors have an important function in the heart. Using a variety of technologies and disease states, we have identified that T1R1, T1R2 and T1R3 are expressed in the heart. More specifically, mass spectrometry of a dog model of dyssynchrony has shown the presence of T1R1, T1R3 and T1R2. RNA seq of human patients who received a Left Ventricular Assist device and those who did not also revealed the presence of T1R1 and T1R3. The expression of these proteins was also confirmed using Western blot. We further showed T1R2 and T1R3 protein is localized in the plasma membrane of the cardiomyocytes by immunofluorescence (colocalized with Na/K ATPase) and PM enrichment. When we compared the taste receptor protein levels in dilated cardiomyopathy (DCM) compared to donor heart tissue, we found that T1R2 was overexpressed in DCM, showing that taste receptors may be important in nutrient sensing in disease. Furthermore, when neonatal rat ventricular myocytes were treated with sweet and umami agonists (aspartame for the sweet taste receptor and monosodium glutamate for the umami receptor), they had increased calcium transients as shown by an increase in peak calcium. Cardiomyocytes treated with aspartame also showed a decrease in time to relax. We hypothesize that in the heart, sweet and umami receptors induce positive inotropy upon a change in nutrient environment.

Genetic preferences for food

Genetic preferences for food

Study on Umami Characteristics of Proline Dipeptides in Fish Sauce Based on STC-1 Cells Taste Sensing Model

This paper aimed to explore the umami characteristic of proline dipeptides in fish sauce. The STC-1 cells taste sensing model was established based on sensory evaluation in this study. Calcium imaging was used to reflect the taste dose effect of proline dipeptides. In order to identify the main receptors that mediate umami taste of proline dipeptides, effects on the mRNA expression of umami receptors (T1R1, T1R3, CaSR and GPRC6a) that dipeptides caused were measured by real-time quantitative PCR. The results showed that none of the 13 proline dipeptides had bitter taste, and most of them presented umami and sour taste. The dipeptides with stronger taste also had lower threshold values, among which the peptides with excellent taste activity were Ser-Pro, Ala-Pro, Pro-Ala, Pro-Val and Pro-Ile. The proline dipeptides with stronger taste activity had stronger upregulation effect on expression of umami taste receptors mRNA, and T1R1 was likely to be an important receptor mediating the umami taste of proline dipeptides. This study provided a non-artificial sensory evaluation method for evaluating umami taste of proline dipeptides in fish sauce, and laid a foundation for further study of quantitative structure-activity relationship of umami oligopeptides in fish sauce.

The umami receptor T1R1\u2013T1R3 heterodimer is rarely formed in chickens

The characterization of molecular mechanisms underlying the taste-sensing system of chickens will add to our understanding of their feeding behaviors in poultry farming. In the mammalian taste system, the heterodimer of taste receptor type 1 members 1/3 (T1R1/T1R3) functions as an umami (amino acid) taste receptor. Here, we analyzed the expression patterns of T1R1 and T1R3 in the taste cells of chickens, labeled by the molecular markers for chicken taste buds (vimentin and α-gustducin). We observed that α-gustducin was expressed in some of the chicken T1R3-positive taste bud cells but rarely expressed in the T1R1-positive and T2R7-positive taste bud cells. These results raise the possibility that there is another second messenger signaling system in chicken taste sensory cells. We also observed that T1R3 and α-gustducin were expressed mostly in the vimentin-positive taste bud cells, whereas T1R1 and bitter taste receptor (i.e., taste receptor type 2 member 7, T2R7) were expressed largely in the vimentin-negative taste bud cells in chickens. In addition, we observed that T1R1 and T1R3 were co-expressed in about 5% of chickens' taste bud cells, which express T1R1 or T1R3. These results suggest that the heterodimer of T1R1 and T1R3 is rarely formed in chickens’ taste bud cells, and they provide comparative insights into the expressional regulation of taste receptors in the taste bud cells of vertebrates.

Polymorphic variants in Sweet and Umami taste receptor genes and birthweight

The first thousand days of life from conception have a significant impact on the health status with short, and long-term effects. Among several anthropometric and maternal lifestyle parameters birth weight plays a crucial role on the growth and neurological development of infants. Recent genome wide association studies (GWAS) have demonstrated a robust foetal and maternal genetic background of birth weight, however only a small proportion of the genetic hereditability has been already identified. Considering the extensive number of phenotypes on which they are involved, we focused on identifying the possible effect of genetic variants belonging to taste receptor genes and birthweight. In the human genome there are two taste receptors family the bitter receptors (TAS2Rs) and the sweet and umami receptors (TAS1Rs). In particular sweet perception is due to a heterodimeric receptor encoded by the TAS1R2 and the TAS1R3 gene, while the umami taste receptor is encoded by the TAS1R1 and the TAS1R3 genes. We observed that carriers of the T allele of the TAS1R1-rs4908932 SNPs showed an increase in birthweight compared to GG homozygotes Coeff: 87.40 (35.13–139.68) p-value = 0.001. The association remained significant after correction for multiple testing. TAS1R1-rs4908932 is a potentially functional SNP and is in linkage disequilibrium with another polymorphism that has been associated with BMI in adults showing the importance of this variant from the early stages of conception through all the adult life.