Molecular basis of the sweet tooth?
Molecular basis of the sweet tooth?
复制标题
爱吃甜食的分子基础？
DOI：
10.1016/s0140-6736(01)07233-6
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Kinnamon,SC
中科院分区：
文献类型：
--
作者：
Chaudhari,N;Kinnamon,SC
在这个节日里，味蕾的甜味将努力工作。这些味蕾检测到的甜味包括氨基酸，如D-苯丙氨酸，甚至一些蛋白质。由于糖和其他高热量食物的过度消费与肥胖和2型糖尿病等疾病有关，因此了解甜味的机制具有广泛的相关性和重要性。其相关性超出了酒精的生理影响。然后是甜味化合物的治疗应用。例如，蔗糖已被用于对抗许多药物的先天苦味，但最近的研究表明，蔗糖释放内啡肽，可用于疼痛管理，特别是在新生儿中，许多镇痛药不适合他们。1味蕾是一群神经上皮感觉细胞，嵌在舌和口腔的皮质上皮中。在舌头的某些区域，例如在舌头背面的一排轮廓状乳头中，味蕾密集地聚集在一起。在其他地方，它们单独分布在软腭上，并在舌头前部的菌状乳头内以两到四个为一组。与教科书中通常展示的“舌头地图”相反，舌头的所有区域都对所有的味道质量（例如，甜，咸）做出反应，尽管效率不同。每个味蕾内都有几十个味觉感受器细胞，每个细胞都能够检测和发出一种或多种味觉品质的信号。当味觉感受器细胞的顶端微绒毛尖端遇到甜味物质时，它们迅速去极化并激发动作电位。这种电活动可能导致神经递质释放到与味觉感受器细胞基底相邻的传入神经纤维（颅神经VII和IX）。结合甜味物质的受体分子可以说是协调这种信号级联的最有趣的分子参与者之一。它们可能是赋予识别甜味物质的特异性的结构，并将这些化合物与那些不被认为是甜味的化合物区分开来。2，3现在有一个了解甜味受体的身份和他们的功能特性的开始。十多年前的一项发现使最近的进展成为可能，即某些近交系小鼠对甜味剂（如蔗糖和糖精）的偏好减弱。[4]相比之下，与非味觉品系相比，味觉品系的小鼠对甜味剂有更高的偏好，其检测阈值较低，传入神经的反应较大。这些差异在很大程度上源于小鼠4号染色体远端附近的一个位点Sac。5，6去年，当人类基因组序列草图公布时，几个实验室独立地扫描了与Sac地图位置同线的人类染色体区域，发现了一个基因Tas 1 r3，它编码一种新的G蛋白偶联受体T1 R3。Tas 1 r3的小鼠同源物尽可能接近Sac，使其成为基因座7 -11 T1 R3以及两个相关的孤儿受体T1 R1和T1 R2的合理候选基因，它们都在味蕾中表达为mRNA，并且它们各自的表达水平在品尝者和非品尝者之间相似。
During this festive season the taste buds for sweetness will be working hard. What these taste buds detect as sweet includes aminoacids such as D-phenylalanine, and even some proteins. Because overconsumption of sugar and other high-calorie foods is associated with disorders such as obesity and type 2 diabetes, understanding the mechanisms of sweet taste is of broad relevance and importance. The relevance extends beyond the physiological effects of the saccharides. Then there are the therapeutic applications of sweet compounds. Sucrose for example, has been used to counter the innately bitter taste of many medicines, but recent studies suggest that sucrose releases endorphins, which can be used in pain management, particularly in newborns, for whom many analgesics are not suitable. 1 Taste buds are clusters of neuroepithelial sensory cells that are embedded in the cornified epithelium of the tongue and oral cavity. In some areas of the tongue, such as in the row of circumvallate papillae across the back of the tongue, taste buds are densely clustered. Elsewhere, they are scattered singly on the soft palate and in groups of two to four within the fungiform papillae that dot the anterior part of the tongue. Contrary to the “tongue maps” commonly displayed in textbooks, all areas of the tongue respond to all the taste qualities (eg, sweet, salty), although with variable efficiency. Within each taste bud are dozens of tastereceptor cells, each of which is able to detect and signal one or more taste qualities. When the apical microvillar tips of taste-receptor cells encounter sweet substances, they rapidly depolarise and fire action potentials. Such electrical activity presumably results in neurotransmitter release on to the afferent nerve fibres (cranial nerves VII and IX) that abut the bases of the taste-receptor cells. The receptor molecules that bind sweet substances are arguably among the most interesting of the molecular players that orchestrate this signalling cascade. They are probably the structures that confer specificity for recognition of sweet substances, and discrimination of these compounds from those that are not perceived as sweet. 2, 3There are now the beginnings of an understanding of the identity of sweet-taste receptors and their functional properties. Recent advances were made possible by the discovery over a decade ago that certain inbred strains of mice have a diminished preference for sweeteners, such as sucrose and saccharin. 4 By contrast, taster strains of mice, which have a higher preference for sweeteners, compared with non-taster strains, have lower thresholds for detection and larger responses in the afferent nerve. These differences stem to a large extent, from a locus, Sac, near the distal end of mouse chromosome 4. 5, 6 Last year, when the draft sequence of the human genome became available, several laboratories independently scanned a human chromosomal region syntenous to the map location of Sac, and discovered a gene, Tas1r3, that encodes a novel G-protein-coupled receptor, T1R3. The mouse homologue of Tas1r3 mapped as closely to Sac as available markers would allow, making it a plausible candidate gene at the locus7-11 T1R3, as well as two related orphan receptors, T1R1 and T1R2, are all expressed as mRNAs in taste buds, and their respective expression levels are similar between taster and non-