Pharmacology of the Umami Taste Receptor

Abstract

Umami, the fifth taste, has been recognized as a legitimate taste modality only recently relative to the other tastes. Dozens of compounds from vastly different chemical classes elicit a savory (also called umami) taste. The prototypical umami substance glutamic acid or its salt monosodium glutamate (MSG) is present in numerous savory food sources or ingredients such as kombu (edible kelp), beans, soy sauce, tomatoes, cheeses, mushrooms, and certain meats and fish. Derivatives of glutamate (Glu), other amino acids, nucleotides, and small peptides can also elicit or modulate umami taste. In addition, many potent umami tasting compounds structurally unrelated to amino acids, nucleotides, and MSG have been either synthesized or discovered as naturally occurring in plants and other substances. Over the last 20 years several receptors have been suggested to mediate umami taste, including members of the metabotropic and ionotropic Glu receptor families, and more recently, the heterodimeric G protein-coupled receptor, T1R1/T1R3. Careful assessment of representative umami tasting molecules from several different chemical classes shows activation of T1R1/T1R3 with the expected rank order of potency in cell-based assays. Moreover, 5′-ribonucleotides, molecules known to enhance the savory note of Glu, considerably enhance the effect of MSG on T1R1/T1R3 in vitro. Binding sites are found on at least 4 distinct locations on T1R1/T1R3, explaining the propensity of the receptor to being activated or modulated by many structurally distinct compounds and these binding sites allosterically interact to modulate receptor activity. Activation of T1R1/T1R3 by all known umami substances evaluated and the receptor’s pharmacological properties are sufficient to explain the basic human sensory experience of savory taste and it is therefore unlikely that other receptors are involved.