Unraveling the biochemistry of sweet and umami tastes

Taste is an important part of everyone's daily life. Sweet taste is particularly important as evidenced by the fact that wars have been fought and people have been enslaved over sugar, the prototypical sweet stimulus (1). Savory taste, often referred to as umami (delicious in Japanese), is also important, its prototypical stimulus being monosodium glutamate (MSG). Despite the importance of these taste sensations to our daily enjoyment of life, until the late 1980s, the biochemical pathways that mediate them were largely unknown. Then, for sweet taste, evidence began to accumulate that it must be by G protein-coupled receptor (GPCR)-mediated. More specifically, it was generally believed to be mediated by several GPCRs because the findings of biochemical, electrophysiological, and psychophysical experiments could only be easily explained by a plurality of receptors (2, 3). And this expectation was supported by the fact that multiple subtypes of GPCRs commonly exist for other important signal molecules (e.g., acetylcholine, norepinephrine, dopamine, serotonin, etc.). Then, in the early 2000s, a breakthrough occurred, dramatically increasing the understanding of both sweet and umami tastes. Nelson et al. (4) reported the discovery of the rat sweetener receptor. In a functional assay, they showed that all substances that rats generalize to sucrose taste are mediated by a single receptor, which is a heterodimer of two GPCRs, T₁R₂ and T₁R₃. Further, they showed that umami taste is also mediated by a heterodimer of the two GPCRs T₁R₁ and T₁R₃. T₁R₁, T₁R₂, and T₁R₃ are members of the small family of class C GPCRs. The most studied members of the class C GPCRs are the homodimeric metabotrophic glutamate (mGluR), heterodimeric γ-aminobutyric acid type B (GABA_{B …}