inosinic-acid and salicin

Interaction between umami and bitter taste has long been observed in human sensory studies and in neural responses in animal models, however, the molecular mechanism for their action has not been delineated. Humans detect diverse bitter compounds using 25-30 members of the type 2 taste receptor (TAS2R) family of G protein-coupled receptor. In this study, we investigated the putative mechanism of antagonism by umami substances using HEK293T cells expressing hTAS2R16 and two known probenecid-insensitive mutant receptors, hTAS2R16 N96T and P44T. In wild type receptor, Glu-Glu, inosine monophosphate (IMP), and l-theanine behave as partial insurmountable antagonists, and monosodium glutamate (MSG) acts as a surmountable antagonist in comparison with probenecid as a full insurmountable antagonist. The synergism with IMP of umami substances still stands in the suppression of hTAS2R16 signaling. In mutagenesis analysis, we found that Glu-Glu, MSG, and l-theanine share at least one critical binding site on N96 and P44 with probenecid. These results provide the first evidence for a direct binding of umami substances to the hTAS2R16 through the probenecid binding pocket on the receptor, resulting in the suppression of bitterness.

Topics: Benzyl Alcohols; Cyclooxygenase Inhibitors; Dipeptides; Glucosides; Glutamates; HEK293 Cells; Humans; Inosine Monophosphate; Protein Binding; Receptors, G-Protein-Coupled; Sodium Glutamate

The antioxidant function and metabolic profiles in mice after dietary supplementation with methionine were investigated. The results showed that methionine supplementation enhanced liver GSH-Px activity and upregulated Gpx1 expression in the liver and SOD1 and Gpx4 expressions in the jejunum. Nrf2/Keap1 is involved in oxidative stress, and the western blotting data exhibited that dietary methionine markedly increased Keap1 abundance, while failed to influence the Nrf2 signal. Metabolomics investigation showed that methionine administration increased 2-hydroxypyridine, salicin, and asparagine and reduced D-Talose, maltose, aminoisobutyric acid, and inosine 5'-monophosphate in the liver, which are widely reported to involve in oxidative stress, lipid metabolism, and nucleotides generation. In conclusion, our study provides insights into antioxidant function and liver metabolic profiles in response to dietary supplementation with methionine.

Topics: Aminoisobutyric Acids; Animals; Antioxidants; Asparagine; Benzyl Alcohols; Diet; Dietary Supplements; Female; Gene Expression Regulation; Glucosides; Glutathione Peroxidase; Glutathione Peroxidase GPX1; Inosine Monophosphate; Jejunum; Kelch-Like ECH-Associated Protein 1; Lactones; Liver; Maltose; Metabolome; Methionine; Mice; Mice, Inbred ICR; NF-E2-Related Factor 2; Phospholipid Hydroperoxide Glutathione Peroxidase; Pyridones; Superoxide Dismutase-1