The Molecular Basis of Individual Differences in Phenylthiocarbamide and Propylthiouracil Bitterness Perception

Abstract

Individual differences in perception are ubiquitous within the chemical senses: taste, smell, and chemical somesthesis . A hypothesis of this fact states that polymorphisms in human sensory receptor genes could alter perception by coding for functionally distinct receptor types . We have previously reported evidence that sequence variants in a presumptive bitter receptor gene (hTAS2R38) correlate with differences in bitterness recognition of phenylthiocarbamide (PTC) . Here, we map individual psychogenomic pathways for bitter taste by testing people with a variety of psychophysical tasks and linking their individual perceptions of the compounds PTC and propylthiouracil (PROP) to the in vitro responses of their TAS2R38 receptor variants. Functional expression studies demonstrate that five different haplotypes from the hTAS2R38 gene code for operatively distinct receptors. The responses of the three haplotypes we also tested in vivo correlate strongly with individuals' psychophysical bitter sensitivities to a family of compounds. These data provide a direct molecular link between heritable variability in bitter taste perception to functional variations of a single G protein coupled receptor that responds to compounds such as PTC and PROP that contain the N-C=S moiety. The molecular mechanisms of perceived bitterness variability have therapeutic implications, such as helping patients to consume beneficial bitter-tasting compounds-for example, pharmaceuticals and selected phytochemicals.

Comprehensive Analysis of Mouse Bitter Taste Receptors Reveals Different Molecular Receptive Ranges for Orthologous Receptors in Mice and Humans

“…9, left and middle panels). A comparison of functionally critical residues in selected TAS2R38 orthologs of the Euarchontoglires clade revealed that all of them invariantly exhibit amino acid residues characteristic for the human taster variant TAS2R38-PAV or a variation thereof (TAS2R38-PAI), which has been experimentally validated for full PTC/PROP responsiveness (33) (Fig. 9, right panel).…”

“…In particular, exchanging tryptophan in position 201 for leucine or phenylalanine caused severely reduced PTC responsiveness and, practically, a loss of activation by PROP. Intriguingly, Trp-5.46 is found only in the haplorrhine primate clade including human and chimpanzee, which exhibit exquisitely PTC-as well as PROP-sensitive TAS2R38 receptors (33,66). Hence, it seems that PTC/PROP-sensitive TAS2R38 evolved within the Primate order in the haplorrhine branch.…”

Genetics of Taste and Smell

“…Although PTC was first created in a chemistry laboratory and is probably not found in plants, there are many chemical relatives of PTC that stimulate the TAS2R38 bitter taste receptor. 39,46,47 At least one of these compounds is found in plant food (turnips), 48 and less similar but still related compounds are found in other plant species. 49 People with taster and nontaster alleles of TAS2R38 differ in their perception of vegetables (like watercress) that contain these PTC-like compounds.…”

“…39 Other bitter molecules stimulate multiple receptors, and the loss of one may decrease but not eliminate the ability to detect that particular bitter molecule. 30,39,47,65-73 The perception of PTC is probably an extreme case of individual variation in bitter perception.…”

Relationships of PROP Taste Phenotype, Taste Receptor Genotype, and Oral Nicotine Replacement Use

“…Carriers of two insensitive alleles (AVI/AVI) are considered non-tasters, and those with at least one sensitive allele (PAV/AVI or PAV/PAV) are considered tasters. 16,17 Genetic analyses support the association between phenotypic taste blindness to PROP and smoking behaviors. For example, a population-based study showed that AVI homozygotes consumed more cigarettes/day than other genotypes.…”