Bitterness receptor

Fig. 36.—Binding of a Bitter-sweet Molecule to a Sweet Receptor- and a Bitter Receptor-site.

Fig. 37.—Binding of One Molecule of a Bitter-sweet Compound to (i) a Sweet Receptor, and of a Second Molecule of the Same Compound to (ii) a Bitter Receptor.

Many bixxer compounds contain both hydrophobic and hydrophilic sites which can alter cell membranes through penetration. There is a correlation between bitter intensity and hydrophobicity-solubility indexes such as fee octanol/water partition coefficient, lo (7). Penetration may directly affect cAMP phosphodiesterase as part of fee transduction process (see below). A bitter receptor protein may be involved wife certain bitters, such as specific structural requirements wife fee bitter tasting dipeptides and denatonium salts (27). The latter is used in some consumer products to avoid accidental ingestion. A receptor mechanism is also supported by fee existence of a genetic "taste blindness" for some bitter materials (see below). 

Fig. 2. Bitterness Receptor Model (Reproduced with permission from ref. 10. Copyright 1988 Japan Society for Bioscience, Biotechnology, and Agrochemistry)...

The general model developed for sweet and bitter compounds leads to a sweet-bitter receptor, which can be given formal representation as a hydrophobic pocket with a bipolar system (Fig. 

Figure 16. Representation of the hydrophobic pocket and the polar contact groups of a formal sweet-bitter receptor...

Shi P, Zhang J. Contrasting modes of evolution between vertebrate sweet/umami receptor genes and bitter receptor genes. Mol. Biol. Evol. 2006 23 292-300. 

Sequencing the Human Genome Led to the Discovery of a Large Family of 7TM Bitter Receptors... 

Figure 32.14. Conserved and Variant Regions in Bitter Receptors. The bitter receptors are members of the 7TM...

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. 

Pronin AN, Xu H, Tang H, Zhang L, Li Q, Li X (2007) Specific alleles of bitter receptor genes influence human sensitivity to the bitterness of aloin and saccharin. Curr Biol 17 1403-1408 Ramirez I, Fuller JL (1976) Genetic influence on water and sweetened water consumption in mice. Physiol Behav 16 163-168... 

Behrens M, Foerster S, Staehler F, Raguse JD, Meyerhof W (2007) Gustatory expression pattern of the human TAS2R bitter receptor gene family reveals a heterogenous population of bitter responsive taste receptor cells. J Neurosci 27 12630-12640 Behrens M, Meyerhof W (2006) Bitter taste receptors and human bitter taste perception. Cell Mol Life Sci 63 1501-1509... 

Arc these proteins, in fact, bitter receptors Several lines of evidence suggest that they are. First, their genes are expressed in taste-sensitive cells — in fact, in many of the same cells that express gustducin. Second, cells that express individual members of this family respond to specific bitter compounds. For example, cells that express a specific mouse receptor (mT2R5) responded when exposed specifically to cycloheximide. Third, mice that had been found unresponsive to cycloheximide were found to have point mutations in the gene encoding mT2R5. Finally, cycloheximide... 

Figure 32.14 Conserved and variant regions in bitter receptors. The bitter receptors are members of the TTM-receptor family. Strongly conserved residues characteristic of this protein family are shown in blue, and highly variable residues are shown in red.

Figure 32.16 Differing gene expression and connection patterns in olfactory and bitter taste receptors., In olfaction, each neuron expresses a single OR gene, and the neurons expressing the same OR converge to specific sites in the brain, enabling specific perception of different odorants. In gustation, each neuron expresses many bitter receptor genes, and so the identity of the tastant is lost in transmission.

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