The molecular basis of individual differences in phenylthiocarbamide and propylthiouracil bitterness perception
The molecular basis of individual differences in phenylthiocarbamide and propylthiouracil bitterness perception
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DOI：
10.1016/j.cub.2005.01.047
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发表时间：
2005-02-22
期刊：
影响因子：
9.2
通讯作者：
Meyerhof, W
中科院分区：
文献类型：
--
作者：
Bufe, B;Breslin, PAS;Meyerhof, W
知觉的个体差异在化学感觉中是普遍存在的：味觉，嗅觉和化学感觉[1-4]。这一事实的一个假设是，人类感觉受体基因的多态性可以通过编码功能不同的受体类型来改变感知[1，5-8]。我们先前报道了推测苦味受体基因（hTAS 2 R38）中的序列变异与苯硫脲（PTC）苦味识别差异相关的证据[9-11]。在这里，我们通过测试具有各种心理物理任务的人，并将他们对PTC和丙基硫氧嘧啶（PROP）的个人感知与其TAS 2 R38受体变体的体外反应联系起来，绘制了苦味的个体心理基因组学途径。功能表达研究表明，来自hTAS 2 R38基因的五种不同单倍型编码可操作地不同的受体。我们还在体内测试了三种单倍型的反应与个体对一系列化合物的心理物理苦味敏感性密切相关。这些数据提供了苦味感知的遗传变异性与单个G蛋白偶联受体的功能变异之间的直接分子联系，该受体对含有N-C=S部分的PTC和PROP等化合物有反应。感知苦味变化的分子机制具有治疗意义，例如帮助患者食用有益的苦味化合物，例如药物和选定的植物化学物质。
Individual differences in perception are ubiquitous within the chemical senses: taste, smell, and chemical somesthesis [1-4]. A hypothesis of this fact states that polymorphisms in human sensory receptor genes could alter perception by coding for functionally distinct receptor types [1, 5-8]. We have previously reported evidence that sequence variants in a presumptive bitter receptor gene (hTAS2R38) correlate with differences in bitterness recognition of phenylthiocarbamide (PTC) [9-11]. 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.