Di Pizio Antonella, Ben Shoshan-Galeczki Yaron, Hayes John E, Niv Masha Y
The Institute of Biochemistry, Food and Nutrition, The Robert H Smith Faculty of Agriculture, Food and Environment, The Hebrew University, 76100, Rehovot, Israel; The Fritz Haber Center for Molecular Dynamics, The Hebrew University, Jerusalem, 91904, Israel.
Department of Food Science, College of Agricultural Sciences, The Pennsylvania State University, University Park PA, USA.
Neurosci Lett. 2019 May 1;700:56-63. doi: 10.1016/j.neulet.2018.04.027. Epub 2018 Apr 19.
"Bitter" and "sweet" are frequently framed in opposition, both functionally and metaphorically, in regard to affective responses, emotion, and nutrition. This oppositional relationship is complicated by the fact that some molecules are simultaneously bitter and sweet. In some cases, a small chemical modification, or a chirality switch, flips the taste from sweet to bitter. Molecules humans describe as bitter are recognized by a 25-member subfamily of class A G-protein coupled receptors (GPCRs) known as TAS2Rs. Molecules humans describe as sweet are recognized by a TAS1R2/TAS1R3 heterodimer of class C GPCRs. Here we characterize the chemical space of bitter and sweet molecules: the majority of bitter compounds show higher hydrophobicity compared to sweet compounds, while sweet molecules have a wider range of sizes. Importantly, recent evidence indicates that TAS1Rs and TAS2Rs are not limited to the oral cavity; moreover, some bitterants are pharmacologically promiscuous, with the hERG potassium channel, cytochrome P450 enzymes, and carbonic anhydrases as common off-targets. Further focus on polypharmacology may unravel new physiological roles for tastant molecules.
在情感反应、情绪和营养方面，“苦”和“甜”在功能和隐喻上常常被视为对立的。这种对立关系因某些分子同时具有苦味和甜味这一事实而变得复杂。在某些情况下，一个微小的化学修饰或手性转换会使味道从甜变苦。被人类描述为苦味的分子由一个名为TAS2Rs的25个成员的A类G蛋白偶联受体（GPCRs）亚家族识别。被人类描述为甜味的分子由C类GPCRs的TAS1R2/TAS1R3异二聚体识别。在这里，我们描述了苦味和甜味分子的化学空间：与甜味化合物相比，大多数苦味化合物表现出更高的疏水性，而甜味分子的大小范围更广。重要的是，最近的证据表明，TAS1Rs和TAS2Rs并不局限于口腔；此外，一些苦味剂具有药理学上的混杂性，常见的脱靶靶点有hERG钾通道、细胞色素P450酶和碳酸酐酶。进一步关注多药理学可能会揭示味觉分子的新生理作用。
