The Sweet Taste Receptor

There is little doubt that Shallenberger s AH,B hypothesis is the most plausible concept in the explanation of the initial stimulation of the sweet-taste receptor. However, it was unfortunate that the evidence was accrued largely with the aid of reducing sugars, which, in solution, equilibrate between many isomers, so that it is not possible to relate total gustatory response to any one particular stereochemical structure It is also not... 

Mixed acetyl-isobutanoyl sucrose esters (SAIB) are used as phase densifiers in beverages.426,427 Sucralose (trichlorogalactosucrose) is produced at the industrial scale and marketed in the UK and other countries as a sweetener, having a 650 times the sweetening power of sucrose.428 Being more stable to heat as compared to other synthetic sweeteners, it can be used in cooking. It has also been shown that the sweet taste of sucralose is based on interactions with both subunits of the sweet-taste receptor.429... 

The low energy sweetening properties of aspartame have been discussed on the basis of structural relationships [1, 83] within the context of the three point contact model of the sweet taste receptor. This model involves a hydrogen bond donor, a hydrogen bond acceptor, and a hydrophobic region with specific geometric relationships. The model accounts for the fact that only one of the four diastereomers of aspartylphenylalanyl methyl ester is sweet. 

Intensive studies on the bitter taste receptor are also in progress, as with the sweet taste receptor.119 In fact, it has been reported that T2R receptors are necessary and sufficient for the detection and perception of bitter... 

Recent work has been conducted to examine sweetener recognition by identifying the receptor molecules in the sweet taste receptor cells biochemically and physiologically. It is thought that intense sweeteners react with membrane receptor proteins connected to a G protein system... 

Scott 2005). Here, we will focus on the detection of sweeteners, with a special emphasis on interactions between sweeteners and the sweet taste receptor. 

Do these diverse compounds give rise to a common perception of sweetness or to qualitatively different sensations Sweetness does indeed appear to be a unitary percept (Breslin et al. 1994,1996). However, some sweeteners may be discriminable on the basis of their activation of other sensory transduction mechanisms or differences in the temporal properties of their sensory action. For example, the sweetener sodium saccharin activates bitter receptors in some people (Kuhn et al. 2004 Pronin et al. 2007), and also inhibits sweet taste at high concentrations (Galindo-Cuspinera et al. 2006). Sweet proteins such as thaumatin and monellin can have a slow onset or evoke a prolonged sweetness compared with sugars (Faus 2000), likely owing to a relatively high affinity for the sweet taste receptor. 

The two subunits of the sweet taste receptor are differentially distributed in the gustatory epithelium. T1R2 is expressed most frequently in taste buds of the cir-cumvallate and foliate papillae (Hoon et al. 1999), less so in palatal taste buds... 

Fig. 1 Topography of the sweet taste receptor. The sweet taste receptor is an integral membrane protein complex composed of two subunits, T1R2 (red) and T1R3 (blue). Each subunit has three main domains a large, extracellular Venus-flytrap domain (VFD) at the amino end of the protein a seven-transmembrane helical domain typical of G-protein-coupled receptors on the carboxyl end and a cysteine-rich linker domain that connects the other two domains...

Esposito V, Gallucci R, Picone D, Saviano G, Tancredi T, Temussi PA (2006) The importance of electrostatic potential in the interaction of sweet proteins with the sweet taste receptor. J Mol Biol 360 448-456... 

FIGURE 4 Three of the most popular indirect models of the active site of the sweet taste receptor. (A) Main contour ofthe active site proposed by Temussi and coworkers (Kamphuis et al., 1992 Temussi et al., 1978,1984,1991), hosting a molecular model of aspartame in an extended conformation. (B) A topological model, developed by Goodman et al. (1987). The L -shaped model and an L -shaped conformation of aspartame are superimposed. The hydrophobic side chain of Phe is denoted X, since it corresponds to the Kier s dispersion point. (C) 3D model of an idealized sweetener proposed by Tinti and Nofre (1991). Besides the AH-B entity, the model has six additional interaction points connected by a complex network of distances. 

The very likely presence in the sweet taste receptor of cavities similar to those hosting Glu in mGluRl, a metabotropic glutamate receptor of known structure (Kunishima et al., 2000), tells us that the sweet taste of small molecular weight sweeteners can certainly be accounted for, even if the details will remain in part obscure, at least till a receptor structure with better resolution than homology models will be available. Can the taste of sweet proteins be also explained by the knowledge of the receptor There is no obvious answer. Let us first examine possible receptor models in detail. 

Like their template, the active conformations of the sweet taste receptor... 

Early indirect models of the active site of the sweet taste receptor tried to... 

Temussi, P.A., Lelj, F., and Tancredi, T. (1978). Three-dimensional mapping of the sweet taste receptor site. ]. Med. Chem. 21,1154-1158. 

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